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Sample records for protein futsch leads

  1. Lead-Binding Proteins: A Review

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    Harvey C. Gonick

    2011-01-01

    Full Text Available Lead-binding proteins are a series of low molecular weight proteins, analogous to metallothionein, which segregate lead in a nontoxic form in several organs (kidney, brain, lung, liver, erythrocyte. Whether the lead-binding proteins in every organ are identical or different remains to be determined. In the erythrocyte, delta-aminolevulinic acid dehydratase (ALAD isoforms have commanded the greatest attention as proteins and enzymes that are both inhibitable and inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD-1, appears to bind lead in a less toxic form. What may be of greater significance is that a low molecular weight lead-binding protein, approximately 10 kDa, appears in the erythrocyte once blood lead exceeds 39 μg/dL and eventually surpasses the lead-binding capacity of ALAD. In brain and kidney of environmentally exposed humans and animals, a cytoplasmic lead-binding protein has been identified as thymosin β4, a 5 kDa protein. In kidney, but not brain, another lead-binding protein has been identified as acyl-CoA binding protein, a 9 kDa protein. Each of these proteins, when coincubated with liver ALAD and titrated with lead, diminishes the inhibition of ALAD by lead, verifying their ability to segregate lead in a nontoxic form.

  2. Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.

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    Coyne, Alyssa N; Yamada, Shizuka B; Siddegowda, Bhavani Bagevalu; Estes, Patricia S; Zaepfel, Benjamin L; Johannesmeyer, Jeffrey S; Lockwood, Donovan B; Pham, Linh T; Hart, Michael P; Cassel, Joel A; Freibaum, Brian; Boehringer, Ashley V; Taylor, J Paul; Reitz, Allen B; Gitler, Aaron D; Zarnescu, Daniela C

    2015-12-15

    RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Isolation of low-molecular-weight lead-binding protein from human erythrocytes

    International Nuclear Information System (INIS)

    Raghavan, S.R.V.; Gonick, H.C.

    1977-01-01

    In blood, lead is mainly associated with erythrocytes and only a very small amount is found in plasma. Previously it was thought that the lead was bound to the erythrocyte cell membrane but more recently it has been observed that lead is bound primarily to the cell contents, ostensibly hemoglobin. In examining the lead-binding properties of normal human erythrocytes and those of lead-exposed industrial workers, we have found that, whereas lead binds only to hemoglobin in normal erythrocytes, there is also appreciable binding of lead to a low-molecular weight-protein in erythrocytes from lead-exposed workers. The synthesis of this protein may be induced by lead exposure. The 10,000 molecular weight protein may act as a storage site and mechanism for segregating lead in a non-toxic form

  4. Lead Intoxication On Protein Fractions, Testicular Tissues And Ameliorative Effect Of ANTOX On Male Albino Rats

    International Nuclear Information System (INIS)

    HASSANIN, M.M.; EL-MAHDY, A.A.; ZAKI, Z.T.; EMARAH, E.A.M.; HUSSEIN, A.M.M.

    2010-01-01

    Lead (heavy metal) was given as lead acetate for two groups of adult male albino rats (Rattus rattus) in drinking water at dose level of 100 mg/litre for 3 and 6 weeks to evaluate its toxic effects on protein and its fractions by using electrophoresis technique, serum testosterone using radioimmunoassay and histological investigation of the testis of male rats.Administration of 100 mg/L lead acetate in drinking water for 3 and 6 weeks induced fluctuated changes in serum total proteins, protein fractions and significant decrease in serum testosterone hormone.Histopathological examination showed cellular changes and degeneration of the seminiferous tubules after 3 and 6 weeks of administration of lead acetate.The treatment of rats with antox (10 mg/kg) during the experimental period caused improvement in protein fraction and testosterone level, and the testes sections appeared more or less normal.

  5. Lead induced changes in phosphorylation of PSII proteins in low light grown pea plants.

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    Wioleta, Wasilewska; Anna, Drożak; Ilona, Bacławska; Kamila, Kąkol; Elżbieta, Romanowska

    2015-02-01

    Light-intensity and redox-state induced thylakoid proteins phosphorylation involved in structural changes and in regulation of protein turnover. The presence of heavy metal ions triggers a wide range of cellular responses including changes in plant growth and photosynthesis. Plants have evolved a number of mechanisms to protect photosynthetic apparatus. We have characterized the effect of lead on PSII protein phosphorylation in pea (Pisum sativum L.) plants grown in low light conditions. Pb ions affected only slightly photochemical efficiency of PSII and had no effect on organization of thylakoid complexes. Lead activated strongly phosphorylation of PSII core D1 protein and dephosphorylation of this protein did not proceed in far red light. D1 protein was also not degraded in this conditions. However, phosphorylation of LHCII proteins was not affected by lead. These results indicate that Pb(2+) stimulate the phosphorylation of PSII core proteins and by disturbing the disassembly of supercomplexes play a role in PSII repair mechanism. LHCII phosphorylation could control the distribution of energy between the photosystems in low light conditions. This demonstrates that plants may respond to heavy metals by induction different pathways responsible for protein protection under stress conditions.

  6. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

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    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B. [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada); Bag, Jnanankur, E-mail: jbag@uoguelph.ca [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada)

    2011-05-13

    Highlights: {yields} Depletion of cellular PABP level arrests mRNA translation in HeLa cells. {yields} PABP knock down leads to apoptotic cell death. {yields} PABP depletion does not affect transcription. {yields} PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  7. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    International Nuclear Information System (INIS)

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B.; Bag, Jnanankur

    2011-01-01

    Highlights: → Depletion of cellular PABP level arrests mRNA translation in HeLa cells. → PABP knock down leads to apoptotic cell death. → PABP depletion does not affect transcription. → PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  8. Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins.

    Science.gov (United States)

    Hanas, J S; Rodgers, J S; Bantle, J A; Cheng, Y G

    1999-11-01

    The association of lead with chromatin in cells suggests that deleterious metal effects may in part be mediated through alterations in gene function. To elucidate if and how lead may alter DNA binding of cysteine-rich zinc finger proteins, lead ions were analyzed for their ability to alter the DNA binding mechanism of the Cys(2)His(2) zinc finger protein transcription factor IIIA (TFIIIA). As assayed by DNase I protection, the interaction of TFIIIA with the 50-bp internal control region of the 5S ribosomal gene was partially inhibited by 5 microM lead ions and completely inhibited by 10 to 20 microM lead ions. Preincubation of free TFIIIA with lead resulted in DNA-binding inhibition, whereas preincubation of a TFIIIA/5S RNA complex with lead did not result in DNA-binding inhibition. Because 5S RNA binds TFIIIA zinc fingers, this result is consistent with an inhibition mechanism via lead binding to zinc fingers. The complete loss of DNase I protection on the 5S gene indicates the mechanism of inhibition minimally involves the N-terminal fingers of TFIIIA. Inhibition was not readily reversible and occurred in the presence of an excess of beta-mercaptoethanol. Inhibition kinetics were fast, progressing to completion in approximately 5 min. Millimolar concentrations of sulfhydryl-specific arsenic ions were not inhibitory for TFIIIA binding. Micromolar concentrations of lead inhibited DNA binding by Sp1, another Cys(2)His(2) finger protein, but not by the nonfinger protein AP2. Inhibition of Cys(2)His(2) zinc finger transcription factors by lead ions at concentrations near those known to have deleterious physiological effects points to new molecular mechanisms for lead toxicity in promoting disease.

  9. Myelin basic protein in brains of rats with low dose lead encephalopathy

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    Sundstroem, R; Karlsson, B

    1987-02-01

    In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1-15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation. The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15-200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.

  10. Interaction betwen Lead and Bone Protein to Affect Bone Calcium Level Using UV-Vis Spectroscopy

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    Noor, Z.; Azharuddin, A.; Aflanie, I.; Kania, N.; Suhartono, E.

    2018-05-01

    This present study aim to evaluate the interactions between lead (Pb) and with bone protein by UV-Vis approach. In addition, this prsent study also aim to investigate the effect of Pb on bone calcium (Ca) level. The present study was a true experimental study design to examine the impact of Pb exposure in bone of male rats (Rattus novergicus). The study involved 5 groups, P1 was the control group, while the other (P2-P5) were the case group with exposure of Pb in different concentration within 4 weeks. At the end of the exposure, the interaction between Pb and protein was determined using UV-Vis spectrophotometric method, and the Ca level was determined using permanganometric method. The results shows that that there is an interaction between Pb and bone protein. The result also shows that the value of the binding constant of Protein-Pb is 32.71. It means Pb have an high affinity to bind with bone protein, which promote a further reaction to induced the release of bone Ca from the bone protein. In conclusion, this present study found an obvious relationship between Pb and bone protein which promote a further reaction to increase the releasing of bone calcium.

  11. Human surfactant protein A2 gene mutations impair dimmer/trimer assembly leading to deficiency in protein sialylation and secretion.

    Directory of Open Access Journals (Sweden)

    Yi Song

    Full Text Available Surfactant protein A2 (SP-A2 plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA, a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2.

  12. Protein malnutrition induces bone marrow mesenchymal stem cells commitment to adipogenic differentiation leading to hematopoietic failure.

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    Cunha, Mayara Caldas Ramos; Lima, Fabiana da Silva; Vinolo, Marco Aurélio Ramirez; Hastreiter, Araceli; Curi, Rui; Borelli, Primavera; Fock, Ricardo Ambrósio

    2013-01-01

    Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states.

  13. Protein Malnutrition Induces Bone Marrow Mesenchymal Stem Cells Commitment to Adipogenic Differentiation Leading to Hematopoietic Failure

    Science.gov (United States)

    Cunha, Mayara Caldas Ramos; Lima, Fabiana da Silva; Vinolo, Marco Aurélio Ramirez; Hastreiter, Araceli; Curi, Rui; Borelli, Primavera; Fock, Ricardo Ambrósio

    2013-01-01

    Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states. PMID:23516566

  14. Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes

    International Nuclear Information System (INIS)

    Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko; Mikami, Toshiyuki; Murayama, Katsuhisa; Arai, Satoko; Miyazaki, Toru

    2012-01-01

    Highlights: ► AIM induces lipolysis in a distinct manner from that of hormone-dependent lipolysis. ► AIM ablates activity of peroxisome proliferator-activated receptor in adipocytes. ► AIM reduces mRNA levels of lipid-droplet coating proteins leading to lipolysis. -- Abstract: Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPARγ), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPARγ-agonist or forced expression of FSP27, while it was synergized by a PPARγ-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological situations; one is a supportive response against nutritional deprivation achieved by

  15. Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

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    Pathan AAK

    2016-05-01

    Full Text Available Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC, Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School of Medicine, Columbia, MO, USA *These authors contributed equally to this work Objective: Kirsten rat sarcoma (K-Ras protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the

  16. STUDY OF INTERACTION BETWEEN LEAD AND GASTRIC MUCOSAL PROTEIN OF RATS WITH FORENSIC TOXICOLOGY APPROACH

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    Iwan Aflanie

    2017-09-01

    Full Text Available Abstract: Recently, forensic toxicology has been an interesting concern, especially in exposing the phenomena associated with the law. Using the forensic toxicology approach, several cases of lead (Pb poisoning have been widely revealed. In this present study will be investigate the interaction between Pb and amino acid gastric mucosal constituent proteins, especially cysteine and tyrosine groups. This research is a pure experimental research with posttest control group design, which is divided into 4 groups with 6 rats (Rattus novergicus in each group. Treatment in each group as follows; P0 was control group were given 2 ml of distilled water; P1 = administration of Pb 0.1 g/L; P2 = Pb administration of 1 mg/L; and P3 = Pb administration of 10 g/L for 4 weeks repectively. According to the results, it can be concluded that Pb-Protein interaction tends to binding of Pb-Cysteine rather than Pb-Tyrosine

  17. Small-molecule inhibitor leads of ribosome-inactivating proteins developed using the doorstop approach.

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    Yuan-Ping Pang

    2011-03-01

    Full Text Available Ribosome-inactivating proteins (RIPs are toxic because they bind to 28S rRNA and depurinate a specific adenine residue from the α-sarcin/ricin loop (SRL, thereby inhibiting protein synthesis. Shiga-like toxins (Stx1 and Stx2, produced by Escherichia coli, are RIPs that cause outbreaks of foodborne diseases with significant morbidity and mortality. Ricin, produced by the castor bean plant, is another RIP lethal to mammals. Currently, no US Food and Drug Administration-approved vaccines nor therapeutics exist to protect against ricin, Shiga-like toxins, or other RIPs. Development of effective small-molecule RIP inhibitors as therapeutics is challenging because strong electrostatic interactions at the RIP•SRL interface make drug-like molecules ineffective in competing with the rRNA for binding to RIPs. Herein, we report small molecules that show up to 20% cell protection against ricin or Stx2 at a drug concentration of 300 nM. These molecules were discovered using the doorstop approach, a new approach to protein•polynucleotide inhibitors that identifies small molecules as doorstops to prevent an active-site residue of an RIP (e.g., Tyr80 of ricin or Tyr77 of Stx2 from adopting an active conformation thereby blocking the function of the protein rather than contenders in the competition for binding to the RIP. This work offers promising leads for developing RIP therapeutics. The results suggest that the doorstop approach might also be applicable in the development of other protein•polynucleotide inhibitors as antiviral agents such as inhibitors of the Z-DNA binding proteins in poxviruses. This work also calls for careful chemical and biological characterization of drug leads obtained from chemical screens to avoid the identification of irrelevant chemical structures and to avoid the interference caused by direct interactions between the chemicals being screened and the luciferase reporter used in screening assays.

  18. Dissecting fragment-based lead discovery at the von Hippel-Lindau protein:hypoxia inducible factor 1α protein-protein interface.

    Science.gov (United States)

    Van Molle, Inge; Thomann, Andreas; Buckley, Dennis L; So, Ernest C; Lang, Steffen; Crews, Craig M; Ciulli, Alessio

    2012-10-26

    Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Mikami, Toshiyuki; Murayama, Katsuhisa [Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022 (Japan); Arai, Satoko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Miyazaki, Toru, E-mail: tm@m.u-tokyo.ac.jp [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer AIM induces lipolysis in a distinct manner from that of hormone-dependent lipolysis. Black-Right-Pointing-Pointer AIM ablates activity of peroxisome proliferator-activated receptor in adipocytes. Black-Right-Pointing-Pointer AIM reduces mRNA levels of lipid-droplet coating proteins leading to lipolysis. -- Abstract: Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPAR{gamma}), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPAR{gamma}-agonist or forced expression of FSP27, while it was synergized by a PPAR{gamma}-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological

  20. A comparison of the effect of lead nitrate on rat liver chromatin, DNA and histone proteins in solution.

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    Rabbani-Chadegani, Azra; Abdosamadi, Sayeh; Fani, Nesa; Mohammadian, Shayesteh

    2009-06-01

    Although lead is widely recognized as a toxic substance in the environment and directly damage DNA, no studies are available on lead interaction with chromatin and histone proteins. In this work, we have examined the effect of lead nitrate on EDTA-soluble chromatin (SE chromatin), DNA and histones in solution using absorption and fluorescence spectroscopy, thermal denaturation and gel electrophoresis techniques. The results demonstrate that lead nitrate binds with higher affinity to chromatin than to DNA and produces an insoluble complex as monitored at 400 nm. Binding of lead to DNA decreases its Tm, increases its fluorescence intensity and exhibits hypochromicity at 210 nm which reveal that both DNA bases and the backbone participate in the lead-DNA interaction. Lead also binds strongly to histone proteins in the absence of DNA. The results suggest that although lead destabilizes DNA structure, in the chromatin, the binding of lead introduces some sort of compaction and aggregation, and the histone proteins play a key role in this aspect. This chromatin condensation, upon lead exposure, in turn may decrease fidelity of DNA, and inhibits DNA and RNA synthesis, the process that introduces lead toxicity at the chromatin level.

  1. System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells.

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    Malina, Halina Z

    2011-01-19

    The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules

  2. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    LENUS (Irish Health Repository)

    Toomey, David

    2009-01-01

    BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins\\/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and\\/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY\\/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS\\/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under \\'change-of-application\\' patents.

  3. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    Directory of Open Access Journals (Sweden)

    David Toomey

    Full Text Available BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i homologous to previously crystallized proteins or (ii targets of known drugs, but are (iii not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.

  4. Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response.

    Science.gov (United States)

    Brown, Marishka K; Strus, Ewa; Naidoo, Nirinjini

    2017-07-01

    Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. D. melanogaster were used to study the effect of social isolation on cellular stress. SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

  5. A Light-Induced Reaction with Oxygen Leads to Chromophore Decomposition and Irreversible Photobleaching in GFP-Type Proteins.

    Science.gov (United States)

    Grigorenko, Bella L; Nemukhin, Alexander V; Polyakov, Igor V; Khrenova, Maria G; Krylov, Anna I

    2015-04-30

    Photobleaching and photostability of proteins of the green fluorescent protein (GFP) family are crucially important for practical applications of these widely used biomarkers. On the basis of simulations, we propose a mechanism for irreversible bleaching in GFP-type proteins under intense light illumination. The key feature of the mechanism is a photoinduced reaction of the chromophore with molecular oxygen (O2) inside the protein barrel leading to the chromophore's decomposition. Using quantum mechanics/molecular mechanics (QM/MM) modeling we show that a model system comprising the protein-bound Chro(-) and O2 can be excited to an electronic state of the intermolecular charge-transfer (CT) character (Chro(•)···O2(-•)). Once in the CT state, the system undergoes a series of chemical reactions with low activation barriers resulting in the cleavage of the bridging bond between the phenolic and imidazolinone rings and disintegration of the chromophore.

  6. Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization

    Energy Technology Data Exchange (ETDEWEB)

    Scaife, R.M. (Fred Hutchinson Cancer Research Center, Seattle, WA (United States)); Wilson, L. (Univ. of California, Santa Barbara (United States)); Purich, D.L. (Univ. of Florida, Gainesville (United States))

    1992-01-14

    Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of ({sup 14}C)NAD{sup +} and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the {alpha} and {beta} chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight microtubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated ({sup 14}C)ADP-ribose to an average extent of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD{sup +} resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.

  7. Benzo[a]pyrene treatment leads to changes in nuclear protein expression and alternative splicing

    Energy Technology Data Exchange (ETDEWEB)

    Yan Chunlan; Wu Wei [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Li Haiyan [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Huzhou Maternity and Child Care Hospital, Huzhou, Zhejiang 313000 (China); Zhang Guanglin [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Duerksen-Hughes, Penelope J. [Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354 (United States); Zhu Xinqiang, E-mail: zhuxq@zju.edu.cn [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Yang Jun, E-mail: gastate@zju.edu.cn [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Zhejiang-California International Nanosystems Institute, Hangzhou, Zhejiang 310029 (China)

    2010-04-01

    Benzo[a]pyrene (BaP) is a potent pro-carcinogen generated from the combustion of fossil fuel and cigarette smoke. Previously, using a proteomic approach, we have shown that BaP can induce changes in the expression of many cellular proteins, including transcription regulators. In the present study, using a similar approach, we examined the nuclear protein response to BaP in HeLa cells and found that BaP treatment caused expression changes in many nuclear proteins. Twenty-four of these proteins were successfully identified, several of which are involved in the alternative splicing of mRNA, DNA replication, recombination, and repair. The changed expression levels were further confirmed by immunoblot analysis using specific antibodies for two proteins, Lamin A and mitotic checkpoint protein Bub3. The nuclear localization of these two proteins was also confirmed by confocal microscopy. To determine whether alternative splicing was activated following BaP treatment, we examined Fas and CD44, two genes previously shown to be targets of alternative splicing in respond to DNA damage. While no significant activation of alternative splicing was observed for Fas, CD44 splicing variants were found after BaP treatment. Together, these data show that DNA damage induces dramatic changes in nuclear protein expression, and that alternative splicing might be involved in the cellular response to DNA damage.

  8. Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients.

    Science.gov (United States)

    Yamamoto, N; Naraparaju, V R; Asbell, S O

    1996-06-15

    Serum vitamin D3-binding protein (Gc protein) can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor of the macrophage activating factor (MAF). Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered MAF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMAF, the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of patient plasma Gc protein was found to be severely reduced in about 25% of this patient population. About 45% of the patients had moderately reduced MAF precursor activities. Loss of the precursor activity was found to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase detected in the patient's bloodstream. The source of the enzyme appeared to be cancerous cells. Radiation therapy decreased plasma alpha-N-acetylgalactosaminidase activity with concomitant increase of precursor activity. This implies that radiation therapy decreases the number of cancerous cells capable of secreting alpha-N-acetylgalactosaminidase. Both alpha-N-acetylgalactosaminidase activity and MAF precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognostic indices.

  9. Fluorescent proteins such as eGFP lead to catalytic oxidative stress in cells.

    Science.gov (United States)

    Ganini, Douglas; Leinisch, Fabian; Kumar, Ashutosh; Jiang, JinJie; Tokar, Erik J; Malone, Christine C; Petrovich, Robert M; Mason, Ronald P

    2017-08-01

    Fluorescent proteins are an important tool that has become omnipresent in life sciences research. They are frequently used for localization of proteins and monitoring of cells [1,2]. Green fluorescent protein (GFP) was the first and has been the most used fluorescent protein. Enhanced GFP (eGFP) was optimized from wild-type GFP for increased fluorescence yield and improved expression in mammalian systems [3]. Many GFP-like fluorescent proteins have been discovered, optimized or created, such as the red fluorescent protein TagRFP [4]. Fluorescent proteins are expressed colorless and immature and, for eGFP, the conversion to the fluorescent form, mature, is known to produce one equivalent of hydrogen peroxide (H 2 O 2 ) per molecule of chromophore [5,6]. Even though it has been proposed that this process is non-catalytic and generates nontoxic levels of H 2 O 2 [6], this study investigates the role of fluorescent proteins in generating free radicals and inducing oxidative stress in biological systems. Immature eGFP and TagRFP catalytically generate the free radical superoxide anion (O 2 •- ) and H 2 O 2 in the presence of NADH. Generation of the free radical O 2 •- and H 2 O 2 by eGFP in the presence of NADH affects the gene expression of cells. Many biological pathways are altered, such as a decrease in HIF1α stabilization and activity. The biological pathways altered by eGFP are known to be implicated in the pathophysiology of many diseases associated with oxidative stress; therefore, it is critical that such experiments using fluorescent proteins are validated with alternative methodologies and the results are carefully interpreted. Since cells inevitably experience oxidative stress when fluorescent proteins are expressed, the use of this tool for cell labeling and in vivo cell tracing also requires validation using alternative methodologies. Published by Elsevier B.V.

  10. Dormancy alleviation by NO or HCN leading to decline of protein carbonylation levels in apple (Malus domestica Borkh.) embryos.

    Science.gov (United States)

    Krasuska, Urszula; Ciacka, Katarzyna; Dębska, Karolina; Bogatek, Renata; Gniazdowska, Agnieszka

    2014-08-15

    Deep dormancy of apple (Malus domestica Borkh.) embryos can be overcome by short-term pre-treatment with nitric oxide (NO) or hydrogen cyanide (HCN). Dormancy alleviation of embryos modulated by NO or HCN and the first step of germination depend on temporary increased production of reactive oxygen species (ROS). Direct oxidative attack on some amino acid residues or secondary reactions via reactive carbohydrates and lipids can lead to the formation of protein carbonyl derivatives. Protein carbonylation is a widely accepted covalent and irreversible modification resulting in inhibition or alteration of enzyme/protein activities. It also increases the susceptibility of proteins to proteolytic degradation. The aim of this work was to investigate protein carbonylation in germinating apple embryos, the dormancy of which was removed by pre-treatment with NO or HCN donors. It was performed using a quantitative spectrophotometric method, while patterns of carbonylated protein in embryo axes were analyzed by immunochemical techniques. The highest concentration of protein carbonyl groups was observed in dormant embryos. It declined in germinating embryos pre-treated with NO or HCN, suggesting elevated degradation of modified proteins during seedling formation. A decrease in the concentration of carbonylated proteins was accompanied by modification in proteolytic activity in germinating apple embryos. A strict correlation between the level of protein carbonyl groups and cotyledon growth and greening was detected. Moreover, direct in vitro carbonylation of BSA treated with NO or HCN donors was analyzed, showing action of both signaling molecules as protein oxidation agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

    Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

    2017-01-01

    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. PMID:28970786

  12. Pulse of inflammatory proteins in the pregnant uterus of European polecats (Mustela putorius) leading to the time of implantation.

    Science.gov (United States)

    Lindeberg, Heli; Burchmore, Richard J S; Kennedy, Malcolm W

    2017-03-01

    Uterine secretory proteins protect the uterus and conceptuses against infection, facilitate implantation, control cellular damage resulting from implantation, and supply pre-implantation embryos with nutrients. Unlike in humans, the early conceptus of the European polecat ( Mustela putorius ; ferret) grows and develops free in the uterus until implanting at about 12 days after mating. We found that the proteins appearing in polecat uteri changed dramatically with time leading to implantation. Several of these proteins have also been found in pregnant uteri of other eutherian mammals. However, we found a combination of two increasingly abundant proteins that have not been recorded before in pre-placentation uteri. First, the broad-spectrum proteinase inhibitor α 2 -macroglobulin rose to dominate the protein profile by the time of implantation. Its functions may be to limit damage caused by the release of proteinases during implantation or infection, and to control other processes around sites of implantation. Second, lipocalin-1 (also known as tear lipocalin) also increased substantially in concentration. This protein has not previously been recorded as a uterine secretion in pregnancy in any species. If polecat lipocalin-1 has similar biological properties to that of humans, then it may have a combined function in antimicrobial protection and transporting or scavenging lipids. The changes in the uterine secretory protein repertoire of European polecats is therefore unusual, and may be representative of pre-placentation supportive uterine secretions in mustelids (otters, weasels, badgers, mink, wolverines) in general.

  13. Random amino acid mutations and protein misfolding lead to Shannon limit in sequence-structure communication.

    Directory of Open Access Journals (Sweden)

    Andreas Martin Lisewski

    2008-09-01

    Full Text Available The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions and in structure (structural defects trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a sensitive to random errors and (b restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials.

  14. Reviewing host proteins of Rhabdoviridae: possible leads for lesser studied viruses.

    Science.gov (United States)

    Guleria, A; Kiranmayi, M; Sreejith, R; Kumar, K; Sharma, S K; Gupta, S

    2011-12-01

    Rhabdoviridae, characterized by bullet-shaped viruses, is known for its diverse host range, which includes plants, arthropods, fishes and humans. Understanding the viral-host interactions of this family can prove beneficial in developing effective therapeutic strategies. The host proteins interacting with animal rhabdoviruses have been reviewed in this report. Several important host proteins commonly interacting with animal rhabdoviruses are being reported, some of which, interestingly, have molecular features, which can serve as potential antiviral targets. This review not only provides the generalized importance of the functions of animal rhabdovirus-associated host proteins for the first time but also compares them among the two most studied viruses, i.e. Rabies virus (RV) and Vesicular Stomatitis virus (VSV). The comparative data can be used for studying emerging viruses such as Chandipura virus (CHPV) and the lesser studied viruses such as Piry virus (PIRYV) and Isfahan virus (ISFV) of the Rhabdoviridae family.

  15. Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

    Science.gov (United States)

    de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

    2018-04-01

    Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

  16. Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

    DEFF Research Database (Denmark)

    Duguez, S.; Duddy, W.; Johnston, H.

    2013-01-01

    Duchenne muscular dystrophy results from loss of the protein dystrophin, which links the intracellular cytoskeletal network with the extracellular matrix, but deficiency in this function does not fully explain the onset or progression of the disease. While some intracellular events involved...... in the degeneration of dystrophin-deficient muscle fibers have been well characterized, changes in their secretory profile are undescribed. To analyze the secretome profile of mdx myotubes independently of myonecrosis, we labeled the proteins of mdx and wild-type myotubes with stable isotope-labeled amino acids...

  17. Protein Targeting: ER Leads the Way to the Inner Nuclear Envelope.

    Science.gov (United States)

    Blackstone, Craig

    2017-12-04

    Efficient targeting of newly synthesized membrane proteins from the endoplasmic reticulum to the inner nuclear membrane depends on nucleotide hydrolysis. A new study shows that this dependence reflects critical actions of the atlastin family of GTPases in maintaining the morphology of the endoplasmic reticulum network. Published by Elsevier Ltd.

  18. Resorufin: a lead for a new protein kinase CK2 inhibitor

    DEFF Research Database (Denmark)

    Sandholt, Iben Skjøth; Olsen, Birgitte Brinkmann; Guerra, Barbara

    2009-01-01

    Screening a natural compound library led to the identification of resorufin as a highly selective and potent inhibitor of protein kinase CK2. Out of 52 kinases tested, only CK2 was inhibited, in contrast to emodin, a structurally related, known CK2 inhibitor that, in addition to CK2, inhibited te...

  19. Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead

    International Nuclear Information System (INIS)

    Stacchiotti, Alessandra; Morandini, Fausta; Bettoni, Francesca; Schena, Ilaria; Lavazza, Antonio; Grigolato, Pier Giovanni; Apostoli, Pietro; Rezzani, Rita; Aleo, Maria Francesca

    2009-01-01

    A close link between stress protein up-regulation and oxidative damage may provide a novel therapeutic tool to counteract nephrotoxicity induced by toxic metals in the human population, mainly in children, of industrialized countries. Here we analysed the time course of the expression of several heat shock proteins, glucose-regulated proteins and metallothioneins in a rat proximal tubular cell line (NRK-52E) exposed to subcytotoxic doses of inorganic mercury and lead. Concomitantly, we used morphological and biochemical methods to evaluate metal-induced cytotoxicity and oxidative damage. In particular, as biochemical indicators of oxidative stress we detected reactive oxygen species (ROS) and nitrogen species (RNS), total glutathione (GSH) and glutathione-S-transferase (GST) activity. Our results clearly demonstrated that mercury increases ROS and RNS levels and the expressions of Hsp25 and inducible Hsp72. These findings are corroborated by evident mitochondrial damage, apoptosis or necrosis. By contrast, lead is unable to up-regulate Hsp72 but enhances Grp78 and activates nuclear Hsp25 translocation. Furthermore, lead causes endoplasmic reticulum (ER) stress, vacuolation and nucleolar segregation. Lastly, both metals stimulate the over-expression of MTs, but with a different time course. In conclusion, in NRK-52E cell line the stress response is an early and metal-induced event that correlates well with the direct oxidative damage induced by mercury. Indeed, different chaperones are involved in the specific nephrotoxic mechanism of these environmental pollutants and work together for cell survival.

  20. Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement

    Science.gov (United States)

    Petojevic, Tatjana; Pesavento, James J.; Costa, Alessandro; Liang, Jingdan; Wang, Zhijun; Berger, James M.; Botchan, Michael R.

    2015-01-01

    DNA replication licensing is now understood to be the pathway that leads to the assembly of double hexamers of minichromosome maintenance (Mcm2–7) at origin sites. Cell division control protein 45 (Cdc45) and GINS proteins activate the latent Mcm2–7 helicase by inducing allosteric changes through binding, forming a Cdc45/Mcm2-7/GINS (CMG) complex that is competent to unwind duplex DNA. The CMG has an active gate between subunits Mcm2 and Mcm5 that opens and closes in response to nucleotide binding. The consequences of inappropriate Mcm2/5 gate actuation and the role of a side channel formed between GINS/Cdc45 and the outer edge of the Mcm2–7 ring for unwinding have remained unexplored. Here we uncover a novel function for Cdc45. Cross-linking studies trace the path of the DNA with the CMG complex at a fork junction between duplex and single strands with the bound CMG in an open or closed gate conformation. In the closed state, the lagging strand does not pass through the side channel, but in the open state, the leading strand surprisingly interacts with Cdc45. Mutations in the recombination protein J fold of Cdc45 that ablate this interaction diminish helicase activity. These data indicate that Cdc45 serves as a shield to guard against occasional slippage of the leading strand from the core channel. PMID:25561522

  1. Dystrophin Hot-Spot Mutants Leading to Becker Muscular Dystrophy Insert More Deeply into Membrane Models than the Native Protein.

    Science.gov (United States)

    Ameziane-Le Hir, Sarah; Paboeuf, Gilles; Tascon, Christophe; Hubert, Jean-François; Le Rumeur, Elisabeth; Vié, Véronique; Raguénès-Nicol, Céline

    2016-07-26

    Dystrophin (DYS) is a membrane skeleton protein whose mutations lead to lethal Duchenne muscular dystrophy or to the milder Becker muscular dystrophy (BMD). One third of BMD "in-frame" exon deletions are located in the region that codes for spectrin-like repeats R16 to R21. We focused on four prevalent mutated proteins deleted in this area (called RΔ45-47, RΔ45-48, RΔ45-49, and RΔ45-51 according to the deleted exon numbers), analyzing protein/membrane interactions. Two of the mutants, RΔ45-48 and RΔ45-51, led to mild pathologies and displayed a similar triple coiled-coil structure as the full-length DYS R16-21, whereas the two others, RΔ45-47 and RΔ45-49, induced more severe pathologies and showed "fractional" structures unrelated to the normal one. To explore lipid packing, small unilamellar liposomes (SUVs) and planar monolayers were used at various initial surface pressures. The dissociation constants determined by microscale thermophoresis (MST) were much higher for the full-length DYS R161-21 than for the mutants; thus the wild type protein has weaker SUV binding. Comparing surface pressures after protein adsorption and analysis of atomic force microscopy images of mixed protein/lipid monolayers revealed that the mutants insert more into the lipid monolayer than the wild type does. In fact, in both models every deletion mutant showed more interactions with membranes than the full-length protein did. This means that mutations in the R16-21 part of dystrophin disturb the protein's molecular behavior as it relates to membranes, regardless of whether the accompanying pathology is mild or severe.

  2. Differential induction of heme oxygenase and other stress proteins in cultured hippocampal astrocytes and neurons by inorganic lead

    International Nuclear Information System (INIS)

    Cabell, Leigh; Ferguson, Charles; Luginbill, Deana; Kern, Marcey; Weingart, Adam; Audesirk, Gerald

    2004-01-01

    We examined the effects of exposure to inorganic lead (Pb 2+ ) on the induction of stress proteins in cultured hippocampal neurons and astrocytes, with particular emphasis on the induction of heme oxygenase-1 (HO-1). In radiolabeled neuronal cultures, Pb 2+ exposure had no significant effect on the synthesis of any protein at any concentration (up to 250 μM) or duration of exposure (up to 4 days). In radiolabeled astrocyte cultures, however, Pb 2+ exposure (100 nM to 100 μM; 1-4 days) increased synthesis of proteins with approximate molecular weights of 23, 32, 45, 57, 72, and 90 kDa. Immunoblot experiments showed that Pb 2+ exposure (100 nM to 10 μM, 1-14 days) induces HO-1 synthesis in astrocytes, but not in neurons; this is probably the 32-kDa protein. The other heme oxygenase isoform, HO-2, is present in both neurons and astrocytes, but is not inducible by Pb 2+ at concentrations up to 100 μM. HO-1 can be induced by a variety of stimuli. We found that HO-1 induction in astrocytes is increased by combined exposure to Pb 2+ and many other stresses, including heat, nitric oxide, H 2 O 2 , and superoxide. One of the stimuli that may induce HO-1 is oxidative stress. Lead exposure causes oxidative stress in many cell types, including astrocytes. Induction of HO-1 by Pb 2+ is reduced by the hydroxyl radical scavengers dimethylthiourea (DMTU) and mannitol, but not by inhibitors of calmodulin, calmodulin-dependent protein kinases, protein kinase C, or extracellular signal-regulated kinases (ERK). Therefore, we conclude that oxidative stress is an important mechanism by which Pb 2+ induces HO-1 synthesis in astrocytes

  3. Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.

    Science.gov (United States)

    Hyun, Seong-In; Weisberg, Andrea; Moss, Bernard

    2017-08-01

    The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into

  4. Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels.

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    Zeyer, Karina A; Reinhardt, Dieter P

    2015-01-01

    Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. They are multi-domain proteins, containing primarily calcium binding epidermal growth factor-like (cbEGF) domains and 8-cysteine/transforming growth factor-beta binding protein-like (TB) domains. Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems. Here, we review the consequences of engineered Marfan syndrome mutations in fibrillin-1 at the protein, cellular and organismal levels. Representative point mutations associated with Marfan syndrome in affected individuals have been introduced and analyzed in recombinant fibrillin-1 fragments. Those mutations affect fibrillin-1 on a structural and functional level. Mutations which impair folding of cbEGF domains can affect protein trafficking. Protein folding disrupted by some mutations can lead to defective secretion in mutant fibrillin-1 fragments, whereas fragments with other Marfan mutations are secreted normally. Many Marfan mutations render fibrillin-1 more susceptible to proteolysis. There is also evidence that some mutations affect heparin binding. Few mutations have been further analyzed in mouse models. An extensively studied mouse model of Marfan syndrome expresses mouse fibrillin-1 with a missense mutation (p.C1039G). The mice display similar characteristics to human patients with Marfan syndrome. Overall, the analyses of engineered mutations leading to Marfan syndrome provide important insights into the pathogenic molecular mechanisms exerted by mutated fibrillin-1. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae.

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    Elena eIlina

    2013-07-01

    Full Text Available Spectinomycin remains a useful reserve option for therapy of gonorrhea. The emergence of multidrug-resistant Neisseria gonorrhoeae strains with decreased susceptibility to cefixime and to ceftriaxone makes it the only medicine still effective for treatment of gonorrhea infection in analogous cases. However, adoption of spectinomycin as a routinely used drug of choice was soon followed by reports of spectinomycin resistance. The main molecular mechanism of spectinomycin resistance in N. gonorrhoeae was C1192T substitution in 16S rRNA genes. Here we reported a Thr-24→Pro mutation in ribosomal protein S5 found in spectinomycin resistant clinical N. gonorrhoeae strain, which carried no changes in 16S rRNA. In a series of experiments, the transfer of rpsE gene allele encoding the mutant ribosomal protein S5 to the recipient N. gonorrhoeae strains was analyzed. The relatively high rate of transformation (ca. 10-5 CFUs indicates the possibility of spread of spectinonycin resistance within gonococcal population due to the horizontal gene transfer.

  6. Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p72 Syk

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    Antonella Pantaleo

    2016-01-01

    Full Text Available In erythrocytes, the regulation of the redox sensitive Tyr phosphorylation of band 3 and its functions are still partially defined. A role of band 3 oxidation in regulating its own phosphorylation has been previously suggested. The current study provides evidences to support this hypothesis: (i in intact erythrocytes, at 2 mM concentration of GSH, band 3 oxidation, and phosphorylation, Syk translocation to the membrane and Syk phosphorylation responded to the same micromolar concentrations of oxidants showing identical temporal variations; (ii the Cys residues located in the band 3 cytoplasmic domain are 20-fold more reactive than GSH; (iii disulfide linked band 3 cytoplasmic domain docks Syk kinase; (iv protein Tyr phosphatases are poorly inhibited at oxidant concentrations leading to massive band 3 oxidation and phosphorylation. We also observed that hemichromes binding to band 3 determined its irreversible oxidation and phosphorylation, progressive hemolysis, and serine hyperphosphorylation of different cytoskeleton proteins. Syk inhibitor suppressed the phosphorylation of band 3 also preventing serine phosphorylation changes and hemolysis. Our data suggest that band 3 acts as redox sensor regulating its own phosphorylation and that hemichromes leading to the protracted phosphorylation of band 3 may trigger a cascade of events finally leading to hemolysis.

  7. Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

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    Emanuele Bernardinelli

    Full Text Available Lipoyl(Octanoyl Transferase 2 (LIPT2 is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell, mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.

  8. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring.

    Science.gov (United States)

    Watkins, Adam J; Wilkins, Adrian; Cunningham, Colm; Perry, V Hugh; Seet, Meei J; Osmond, Clive; Eckert, Judith J; Torrens, Christopher; Cagampang, Felino R A; Cleal, Jane; Gray, William P; Hanson, Mark A; Fleming, Tom P

    2008-04-15

    Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P size or nephron number was altered by diet treatment (P < 0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.

  9. Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis.

    Science.gov (United States)

    Moreno-Morcillo, María; Grande-García, Araceli; Ruiz-Ramos, Alba; Del Caño-Ochoa, Francisco; Boskovic, Jasminka; Ramón-Maiques, Santiago

    2017-06-06

    CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

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    Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

    2016-07-01

    Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. Copyright © 2016 the American Physiological Society.

  11. Role of S-layer proteins in the biosorption capacity of lead by Lactobacillus kefir.

    Science.gov (United States)

    Gerbino, Esteban; Carasi, Paula; Araujo-Andrade, Cuauhtémoc; Tymczyszyn, E Elizabeth; Gómez-Zavaglia, Andrea

    2015-04-01

    The role of S-layer proteins (SLP) on the Pb(2+) sequestrant capacity by Lactobacillus kefir CIDCA 8348 and JCM 5818 was investigated. Cultures in the stationary phase were treated with proteinase K. A dot blot assay was carried out to assess the removal of SLP. Strains with and without SLP were exposed to 0-0.5 mM Pb(NO3)2. The maximum binding capacity (q max ) and the affinity coefficient (b) were calculated using the Langmuir equation. The structural effect of Pb(2+) on microorganisms with and without SLP was determined using Raman spectroscopy. The bacterial interaction with Pb(2+) led to a broadening in the phosphate bands (1,300-1,200 cm(-1) region) and strong alterations on amide and carboxylate-related bands (νCOO(-) as and νCOO(-) s). Microorganisms without SLP removed higher percentages of Pb(2+) and had higher q max than those bearing SLP. Isolated SLP had much lower q max and also removed lower percentages of Pb(2+) than the corresponding whole microorganisms. The hydrofobicity of both strains dramatically dropped when removing SLP. When bearing SLP, strains do not expose a large amount of charged groups on their surfaces, thus making less efficient the Pb(2+) removal. On the contrary, the extremely low hydrofobicity of microorganisms without SLP (and consequently, their higher capacity to remove Pb(2+)) can be explained on the basis of a greater exposure of charged chemical groups for the interaction with Pb(2+). The viability of bacteria without SLP was not significantly lower than that of bacteria bearing SLP. However, microorganisms without SLP were more prone to the detrimental effect of Pb(2+), thus suggesting that SLP acts as a protective rather than as a sequestrant layer.

  12. NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.

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    Dias, David M; Ciulli, Alessio

    2014-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. The conserved, disease-associated RNA binding protein dNab2 interacts with the Fragile-X protein ortholog in Drosophila neurons

    Science.gov (United States)

    Bienkowski, Rick S.; Banerjee, Ayan; Rounds, J. Christopher; Rha, Jennifer; Omotade, Omotola F.; Gross, Christina; Morris, Kevin J.; Leung, Sara W.; Pak, ChangHui; Jones, Stephanie K.; Santoro, Michael R.; Warren, Stephen T.; Zheng, James Q.; Bassell, Gary J.; Corbett, Anita H.; Moberg, Kenneth H.

    2017-01-01

    Summary The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA-binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with and the Fragile-X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII but not futsch mRNA, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A)-tail length similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. In sum these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14. PMID:28793261

  14. The Conserved, Disease-Associated RNA Binding Protein dNab2 Interacts with the Fragile X Protein Ortholog in Drosophila Neurons

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    Rick S. Bienkowski

    2017-08-01

    Full Text Available The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII, but not futsch, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A tail length, similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. Altogether, these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14.

  15. In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

    Science.gov (United States)

    Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

    1992-04-01

    A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

  16. Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells.

    Science.gov (United States)

    Woods, Alison J; Roberts, Marnie S; Choudhary, Jyoti; Barry, Simon T; Mazaki, Yuichi; Sabe, Hisataka; Morley, Simon J; Critchley, David R; Norman, Jim C

    2002-02-22

    Using mass spectrometry we have identified proteins which co-immunoprecipitate with paxillin, an adaptor protein implicated in the integrin-mediated signaling pathways of cell motility. A major component of paxillin immunoprecipitates was poly(A)-binding protein 1, a 70-kDa mRNA-binding protein. Poly(A)-binding protein 1 associated with both the alpha and beta isoforms of paxillin, and this was unaffected by RNase treatment consistent with a protein-protein interaction. The NH(2)-terminal region of paxillin (residues 54-313) associated directly with poly(A)-binding protein 1 in cell lysates, and with His-poly(A)-binding protein 1 immobilized in microtiter wells. Binding was specific, saturable and of high affinity (K(d) of approximately 10 nm). Cell fractionation studies showed that at steady state, the bulk of paxillin and poly(A)-binding protein 1 was present in the "dense" polyribosome-associated endoplasmic reticulum. However, inhibition of nuclear export with leptomycin B caused paxillin and poly(A)-binding protein 1 to accumulate in the nucleus, indicating that they shuttle between the nuclear and cytoplasmic compartments. When cells migrate, poly(A)-binding protein 1 colocalized with paxillin-beta at the tips of lamellipodia. Our results suggest a new mechanism whereby a paxillin x poly(A)-binding protein 1 complex facilitates transport of mRNA from the nucleus to sites of protein synthesis at the endoplasmic reticulum and the leading lamella during cell migration.

  17. Incorporation of Ortho- and Meta-Tyrosine Into Cellular Proteins Leads to Erythropoietin-Resistance in an Erythroid Cell Line

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    Esztella Mikolás

    2014-04-01

    Full Text Available Background/Aims: Erythropoietin-resistance is an unsolved concern in the treatment of renal anaemia. We aimed to investigate the possible role of ortho- and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in the development of erythropoietin-resistance. Methods: TF-1 erythroblast cell line was used. Cell concentration was determined on day 1; 2 and 3 by two independent observers simultaneously in Bürker cell counting chambers. Protein concentration was determined with colorimetric method. Para-, ortho- and meta-tyrosine levels were measured using reverse phase-HPLC with fluorescence detection. Using Western blot method activating phosphorylation of STAT5 and ERK1/2 were investigated. Results: We found a time- and concentration-dependent decrease of erythropoietin-induced proliferative activity in case of ortho- and meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured cells. Decreased erythropoietin-response could be regained with a competitive dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta-tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content. Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically prevented by ortho- or meta-tyrosine treatment. Conclusion: According to this study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the dysfunction of intracellular signaling, resulting in erythropoietin-hyporesponsiveness.

  18. Lipophilic organic pollutants induce changes in phospholipid and membrane protein composition leading to Vero cell morphological change.

    Science.gov (United States)

    Liao, Ting T; Wang, Lei; Jia, Ru W; Fu, Xiao H; Chua, Hong

    2014-01-01

    Membrane damage related to morphological change in Vero cells is a sensitive index of the composite biotoxicity of trace lipophilic chemicals. However, judging whether the morphological change in Vero cells happens and its ratio are difficult because it is not a quantitative characteristic. To find biomarkers of cell morphological change for quantitatively representing the ratio of morphological changed cell, the mechanism of cell membrane damage driven by typical lipophilic chemicals, such as trichlorophenol (TCP) and perfluorooctanesulphonate (PFOS), was explored. The ratio of morphologically changed cells generally increased with increased TCP or PFOS concentrations, and the level of four major components of phospholipids varied with concentrations of TCP or PFOS, but only the ratio of phosphatidylcholine (PC)/phosphatidylethanolamine (PE) decreased regularly as TCP or PFOS concentrations increased. Analysis of membrane proteins showed that the level of vimentin in normal cell membranes is high, while it decreases or vanishes after TCP exposure. These variations in phospholipid and membrane protein components may result in membrane leakage and variation in rigid structure, which leads to changes in cell morphology. Therefore, the ratio of PC/PE and amount of vimentin may be potential biomarkers for representing the ratio of morphological changed Vero cell introduced by trace lipophilic compounds, thus their composite bio-toxicity.

  19. Expression of the recombinant bacterial outer surface protein A in tobacco chloroplasts leads to thylakoid localization and loss of photosynthesis.

    Science.gov (United States)

    Hennig, Anna; Bonfig, Katharina; Roitsch, Thomas; Warzecha, Heribert

    2007-11-01

    Bacterial lipoproteins play crucial roles in host-pathogen interactions and pathogenesis and are important targets for the immune system. A prominent example is the outer surface protein A (OspA) of Borrelia burgdorferi, which has been efficiently used as a vaccine for the prevention of Lyme disease. In a previous study, OspA could be produced in tobacco chloroplasts in a lipidated and immunogenic form. To further explore the potential of chloroplasts for the production of bacterial lipoproteins, the role of the N-terminal leader sequence was investigated. The amount of recombinant OspA could be increased up to ten-fold by the variation of the insertion site in the chloroplast genome. Analysis of OspA mutants revealed that replacement of the invariant cysteine residue as well as deletion of the leader sequence abolishes palmitolyation of OspA. Also, decoration of OspA with an N-terminal eukaryotic lipidation motif does not lead to palmitoylation in chloroplasts. Strikingly, the bacterial signal peptide of OspA efficiently targets the protein to thylakoids, and causes a mutant phenotype. Plants accumulating OspA at 10% total soluble protein could not grow without exogenously supplied sugars and rapidly died after transfer to soil under greenhouse conditions. The plants were found to be strongly affected in photosystem II, as revealed by the analyses of temporal and spatial dynamics of photosynthetic activity by chlorophyll fluorescence imaging. Thus, overexpression of OspA in chloroplasts is limited by its concentration-dependent interference with essential functions of chloroplastic membranes required for primary metabolism.

  20. 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.

  1. Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by temperature in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Yunbiao; Xu, Songbai; Liu, Jing; Zhang, Yanhui; Guo, Tai L

    2014-06-01

    In the nematode Caenorhabditis elegans, stress resistance can be regulated by dauer formation (daf) genes. In the present study, regulation of heavy metal lead (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects of varied temperatures below (15°C) or above (25 and 30°C) the presumptive optimum growth temperature (20°C). More acute toxicity of Pb, indicated by the 24-h median lethal concentrations (LC50), was observed in wild-type adults than in the daf-21 mutant adults at 15, 20 and 25°C; however, the daf-21 mutant adults showed more sensitivity at 30°C. Enhanced Pb sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with both increased and decreased temperatures when compared to that at 20°C. Additional examined endpoints included time course of toxicity at LC50s, pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective results showed that temperatures both above and below 20°C exacerbated Pb toxicity, and that the protein level of daf-21/Hsp90 was one of the most sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf-21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced toxicity in nematodes. Further, the stress responses related to Hsp90 expression in C. elegans may have considerable potential as sensitive biomarkers for the monitoring of environmental Pb contamination. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

    Science.gov (United States)

    Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

    2009-08-04

    Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

  3. Lead (Pb+2) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity

    International Nuclear Information System (INIS)

    Vazquez, Adrinel; Pena de Ortiz, Sandra

    2004-01-01

    The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca 2+ ) and cyclic adenosine monophosphate as second messengers. In particular, Ca +2 /phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb +2 ) has been associated to its interference with normal Ca +2 signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na + or Pb +2 acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb +2 did not affect learning of the task, but significantly impaired retention. The effects of Pb +2 selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb +2 on the induction of hippocampal Ca +2 /phospholipid-dependent PKC activity during acquisition training. The results showed that Pb +2 interfered with the learning-induced activation of Ca +2 /phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb +2 causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca +2 -related signaling mechanisms required for normal LTM

  4. Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1.

    Science.gov (United States)

    Csorba, Tibor; Lózsa, Rita; Hutvágner, György; Burgyán, József

    2010-05-01

    RNA silencing plays an important role in plants in defence against viruses. To overcome this defence, plant viruses encode suppressors of RNA silencing. The most common mode of silencing suppression is sequestration of double-stranded RNAs involved in the antiviral silencing pathways. Viral suppressors can also overcome silencing responses through protein-protein interaction. The poleroviral P0 silencing suppressor protein targets ARGONAUTE (AGO) proteins for degradation. AGO proteins are the core component of the RNA-induced silencing complex (RISC). We found that P0 does not interfere with the slicer activity of pre-programmed siRNA/miRNA containing AGO1, but prevents de novo formation of siRNA/miRNA containing AGO1. We show that the AGO1 protein is part of a high-molecular-weight complex, suggesting the existence of a multi-protein RISC in plants. We propose that P0 prevents RISC assembly by interacting with one of its protein components, thus inhibiting formation of siRNA/miRNA-RISC, and ultimately leading to AGO1 degradation. Our findings also suggest that siRNAs enhance the stability of co-expressed AGO1 in both the presence and absence of P0.

  5. Protein precipitation of diluted samples in SDS-containing buffer with acetone leads to higher protein recovery and reproducibility in comparison with TCA/acetone approach.

    Science.gov (United States)

    Santa, Cátia; Anjo, Sandra I; Manadas, Bruno

    2016-07-01

    Proteomic approaches are extremely valuable in many fields of research, where mass spectrometry methods have gained an increasing interest, especially because of the ability to perform quantitative analysis. Nonetheless, sample preparation prior to mass spectrometry analysis is of the utmost importance. In this work, two protein precipitation approaches, widely used for cleaning and concentrating protein samples, were tested and compared in very diluted samples solubilized in a strong buffer (containing SDS). The amount of protein recovered after acetone and TCA/acetone precipitation was assessed, as well as the protein identification and relative quantification by SWATH-MS yields were compared with the results from the same sample without precipitation. From this study, it was possible to conclude that in the case of diluted samples in denaturing buffers, the use of cold acetone as precipitation protocol is more favourable than the use of TCA/acetone in terms of reproducibility in protein recovery and number of identified and quantified proteins. Furthermore, the reproducibility in relative quantification of the proteins is even higher in samples precipitated with acetone compared with the original sample. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Fish Protein Concentrate Fortification Siam Patin on Amplang Snack Products and Mi Sago Instant Product as a Leading Regional Riau

    Directory of Open Access Journals (Sweden)

    Dewita Buchari

    2014-11-01

    Full Text Available To enhance fish consumption in the community especially children, fortification on processed fish product is conducted. The processed fish products are developed to fill the requirements as the fish based food products that own characterizations such as ready to eat, easy to carry, and less time to cook. Amplang snacks and instant sagoo noodles are defined as the products that fills the requirements. The research was aimed to process catfish into fish protein concentrate to become amplang snack and instant sagoo noodles. These products were designed as the effort to develop the local priority products in Riau by using diversification and fortification methods. Experimental method with fortification treatments on Fish Protein Concentrate (FPC extract from Catfish that generate products of amplang snacks and instant sagoo noodles and fish tofu were carried out. The fortified products were examined by organoleptics test that involved panelists. The results showed that the proximate analysis on fortified Catfish Protein Concentrate products were presented as following :1. water contents of 3,13 %, ash of 2,85 %, protein content of 16,13 % and fat content of 18, 66 % for ampang snacks; and 2. water contents of 11,77 %, ash of 1,30 %, protein content of 12,35 % and fat content of 1,86 % for instant sagoo nodles. All fortified FPC products filled the Indonesian Nasional Standard (SNI.Keywords: Fortification, Catfish, and Fish Protein Concentrate

  7. Mutant uromodulin expression leads to altered homeostasis of the endoplasmic reticulum and activates the unfolded protein response.

    Directory of Open Access Journals (Sweden)

    Céline Schaeffer

    Full Text Available Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD, characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER, is well established, its downstream effects are still largely unknown. To gain insight into ADTKD-UMOD pathogenesis, we performed transcriptional profiling and biochemical characterisation of cellular models (immortalised mouse TAL cells of robust expression of wild type or mutant GFP-tagged uromodulin. In this model mutant uromodulin accumulation in the ER does not impact on cell viability and proliferation. Transcriptional profiling identified 109 genes that are differentially expressed in mutant cells relative to wild type ones. Up-regulated genes include several ER resident chaperones and protein disulphide isomerases. Consistently, pathway enrichment analysis indicates that mutant uromodulin expression affects ER function and protein homeostasis. Interestingly, mutant uromodulin expression induces the Unfolded Protein Response (UPR, and specifically the IRE1 branch, as shown by an increased splicing of XBP1. Consistent with UPR induction, we show increased interaction of mutant uromodulin with ER chaperones Bip, calnexin and PDI. Using metabolic labelling, we also demonstrate that while autophagy plays no role, mutant protein is partially degraded by the proteasome through ER-associated degradation. Our work demonstrates that ER stress could play a central role in ADTKD-UMOD pathogenesis. This sets the bases for future work to develop novel therapeutic strategies through modulation of ER homeostasis and

  8. Complete deficiency of mitochondrial trifunctional protein due to a novel mutation within the beta-subunit of the mitochondrial trifunctional protein gene leads to failure of long-chain fatty acid beta-oxidation with fatal outcome

    NARCIS (Netherlands)

    Schwab, Karl Otfried; Ensenauer, Regina; Matern, Dietrich; Uyanik, Gökhan; Schnieders, Birgit; Wanders, Ronald A.; Lehnert, Willy

    2003-01-01

    The mitochondrial trifunctional protein (MTP) is a multienzyme complex which catalyses three of the four chain-shortening reactions in the beta-oxidation of long-chain fatty acids. Clinically, failure of long-chain fatty acid beta-oxidation leads to hypoketotic hypoglycaemia associated with coma,

  9. Protein kinase A phosphorylates serine 267 in the homeodomain of engrailed-2 leading to decreased DNA binding

    DEFF Research Database (Denmark)

    Hjerrild, Majbrit; Stensballe, Allan; Jensen, Ole N

    2004-01-01

    Engrailed-2 (En-2) belongs to an evolutionarily conserved family of DNA binding homeodomain-containing proteins that are expressed in mammalian brain during development. Here, we demonstrate that serine 267 in the homeodomain of En-2 is phosphorylated by protein kinase A (PKA) in forskolin......-treated COS-7 cells. Furthermore, we analyze the physiological function of En-2 phosphorylation by PKA. The nuclear localization of En-2 is not influenced by the phosphorylation of serine 267. However, substitution of serine 267 with alanine resulted in increased binding of En-2 to DNA, while replacing serine...

  10. Lead Discovery for Alzheimer’s Disease Related Target Protein RbAp48 from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Hung-Jin Huang

    2014-01-01

    Full Text Available Deficiency or loss of function of Retinoblastoma-associated proteins (RbAp48 is related with Alzheimer’s disease (AD, and AD disease is associated with age-related memory loss. During normal function, RbAp48 forms a complex with the peptide FOG-1 (friend of GATA-1 and has a role in gene transcription, but an unstable complex may affect the function of RbAp48. This study utilizes the world’s largest traditional Chinese medicine (TCM database and virtual screening to provide potential compounds for RbAp48 binding. A molecular dynamics (MD simulation was employed to understand the variations after protein-ligand interaction. FOG1 was found to exhibit low stability after RbAp48 binding; the peptide displayed significant movement from the initial docking position, a phenomenon which matched the docking results. The protein structure of the other TCM candidates was not variable during MD simulation and had a greater stable affinity for RbAp48 binding than FOG1. Our results reveal that the protein structure does not affect ligand binding, and the top three TCM candidates Bittersweet alkaloid II, Eicosandioic acid, and Perivine might resolve the instability of the RbAp48-FOG1 complex and thus be used in AD therapy.

  11. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I.

    Science.gov (United States)

    Strand, Deserah D; Livingston, Aaron K; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M; Fisher, Nicholas; Froehlich, John E; Cruz, Jeffrey A; Minhas, Deepika; Hixson, Kim K; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M

    2016-01-01

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 ( hcef2 ) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force ( pmf ), activation of the photoprotective q E response, and the accumulation of H 2 O 2 . Surprisingly, hcef2 was mapped to a non-sense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex, and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash-induced thylakoid electric field suggest that these defect lead to accumulation of H 2 O 2 in hcef2 , which we have previously shown leads to activation of NDH-related CEF. We observed similar increases in CEF, as well as increases in H 2 O 2 accumulation, in other translation defective mutants. This suggests that loss of coordination in plastid protein levels lead to imbalances in photosynthetic energy balance that leads to an increase in CEF. These results taken together with a large body of previous observations, support a general model in which processes that lead to imbalances in chloroplast energetics result in the production of H 2 O 2 , which in turn activates CEF. This activation could be from either H 2 O 2 acting as a redox signal, or by a secondary effect from H 2 O 2 inducing a deficit in ATP.

  12. Decreasing the amount of trypsin in in-gel digestion leads to diminished chemical noise and improved protein identifications.

    Science.gov (United States)

    Hu, Mo; Liu, Yanhua; Yu, Kaiwen; Liu, Xiaoyun

    2014-09-23

    Pre-fractionation by gel electrophoresis is often combined with liquid chromatography-mass spectrometry (LC-MS) for large-scale profiling of complex protein samples. An essential component of this widely applied proteomic platform is in-gel protein digestion. In nearly two decades of practicing this approach, an extremely high level of trypsin has been utilized due to the consideration of slow enzyme diffusion into the gel matrix. Here we report that trypsin autolysis products contribute to the bulk of chemical noise in in-gel digestion and remarkably we found evidence that the amount of trypsin can be slashed by an order of magnitude with comparable digestion performance. By revising perhaps the most critical element of this decade-old digestion protocol, the proteomics community relying on gel separation prior to LC-MS analysis will benefit instantly from much lowered cost due to enzyme expenditure. More importantly, substantially reduced chemical noise (i.e., trypsin self-cleavage products) as a result of less enzyme usage translates into more protein identifications when limited amounts of samples are the interest of interrogation. In-gel digestion is one of the most widely used methods in proteomics. An exceedingly high level of trypsin has been utilized due to the consideration of slow enzyme diffusion into the gel matrix. This requirement has been faithfully kept in nearly two decades of practicing this approach. Here we report that trypsin concentration can be slashed by at least an order of magnitude while still providing comparable digestion performance. Thus the proteomics community relying on gel separation prior to LC-MS analysis will benefit instantly from much lowered enzyme cost. More importantly, substantially reduced chemical noise (i.e., trypsin autolysis products) due to less enzyme usage translates into ~30% more protein identifications when limited amounts of protein samples are analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Protein kinase A (PKA) phosphorylation of Na+/K+-ATPase opens intracellular C-terminal water pathway leading to third Na+-binding site in molecular dynamics simulations

    DEFF Research Database (Denmark)

    Poulsen, Hanne; Nissen, Poul; Mouritsen, Ole G.

    2012-01-01

    -atom Molecular Dynamics (MD) simulations to investigate the structural consequences of phosphorylating the Na+/K+- ATPase (NKA) residue S936, which is the best characterized phosphorylation site in NKA, targeted in vivo by Protein Kinase A (PKA) (1-3). The MD simulations suggest that S936 phosphorylation opens......Phosphorylation is one of the major mechanisms for posttranscriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all...... a C-terminal hydrated pathway leading to D926, a transmembrane residue proposed to form part of the third sodium ion-binding site (4). Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic...

  14. A low-protein diet combined with low-dose endotoxin leads to changes in glucose homeostasis in weanling rats

    NARCIS (Netherlands)

    Bandsma, Robert H. J.; Ackerley, Cameron; Koulajian, Khajag; Zhang, Ling; van Zutphen, Tim; van Dijk, Theo H.; Xiao, Changting; Giacca, Adria; Lewis, Gary F.

    2015-01-01

    Severe malnutrition is a leading cause of global childhood mortality, and infection and hypoglycemia or hyperglycemia are commonly present. The etiology behind the changes in glucose homeostasis is poorly understood. Here, we generated an animal model of severe malnutrition with and without

  15. Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in Hepatitis C virus replicon

    Directory of Open Access Journals (Sweden)

    Luftig Ronald

    2007-09-01

    Full Text Available Abstract Background Alpha interferon in combination with ribavirin is the standard therapy for hepatitis C virus infection. Unfortunately, a significant number of patients fail to eradicate their infection with this regimen. The mechanisms of IFN-resistance are unclear. The aim of this study was to determine the contribution of host cell factors to the mechanisms of interferon resistance using replicon cell lines. Results HCV replicons with high and low activation of the IFN-promoter were cultured for a prolonged period of time in the presence of interferon-alpha (IFN-alpha2b. Stable replicon cell lines with resistant phenotype were isolated and characterized by their ability to continue viral replication in the presence of IFN-alpha. Interferon resistant cell colonies developed only in replicons having lower activation of the IFN promoter and no resistant colonies arose from replicons that exhibit higher activation of the IFN promoter. Individual cell clones were isolated and nine IFN resistant cell lines were established. HCV RNA and protein levels in these cells were not altered by IFN- alpha2b. Reduced signaling and IFN-resistant phenotype was found in all Huh-7 cell lines even after eliminating HCV, suggesting that cellular factors are involved. Resistant phenotype in the replicons is not due to lack of interferon receptor expression. All the cell lines show defect in the JAK-STAT signaling and phosphorylation of STAT 1 and STAT 2 proteins were strongly inhibited due to reduced expression of Tyk2 and Jak-1 protein. Conclusion This in vitro study provides evidence that altered expression of the Jak-Stat signaling proteins can cause IFN resistance using HCV replicon cell clones.

  16. An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure.

    Science.gov (United States)

    Razzaque, Md Abdur; Gupta, Manish; Osinska, Hanna; Gulick, James; Blaxall, Burns C; Robbins, Jeffrey

    2013-08-16

    A stable 40-kDa fragment is produced from cardiac myosin-binding protein C when the heart is stressed using a stimulus, such as ischemia-reperfusion injury. Elevated levels of the fragment can be detected in the diseased mouse and human heart, but its ability to interfere with normal cardiac function in the intact animal is unexplored. To understand the potential pathogenicity of the 40-kDa fragment in vivo and to investigate the molecular pathways that could be targeted for potential therapeutic intervention. We generated cardiac myocyte-specific transgenic mice using a Tet-Off inducible system to permit controlled expression of the 40-kDa fragment in cardiomyocytes. When expression of the 40-kDa protein is induced by crossing the responder animals with tetracycline transactivator mice under conditions in which substantial quantities approximating those observed in diseased hearts are reached, the double-transgenic mice subsequently experience development of sarcomere dysgenesis and altered cardiac geometry, and the heart fails between 12 and 17 weeks of age. The induced double-transgenic mice had development of cardiac hypertrophy with myofibrillar disarray and fibrosis, in addition to activation of pathogenic MEK-ERK pathways. Inhibition of MEK-ERK signaling was achieved by injection of the mitogen-activated protein kinase (MAPK)/ERK inhibitor U0126. The drug effectively improved cardiac function, normalized heart size, and increased probability of survival. These results suggest that the 40-kDa cardiac myosin-binding protein C fragment, which is produced at elevated levels during human cardiac disease, is a pathogenic fragment that is sufficient to cause hypertrophic cardiomyopathy and heart failure.

  17. Induced synthesis of toroid-like lead sulfide nanocomposites in ethanol solution through a protein templating route

    International Nuclear Information System (INIS)

    Zhang, Li; Qin, Dezhi; Yang, Guangrui; Du, Xian; Zhang, Qiuxia; Li, Feng

    2015-01-01

    The toroid-like PbS nanocrystals have been prepared in zein ethanol solution based on self-assembly template of protein molecules. From transmission electron microscopy observation, the obtained samples were monodispersed with an average size of about 47 nm. The chemical composition and crystal structure of nanocomposites were determined by X-ray diffraction and energy-dispersive X-ray spectrum measurements. The interaction between PbS and zein was investigated through Fourier transform infrared, photoluminescence, circular dichroism (CD) spectra, and thermogravimetric analysis. The PbS nanocrystals could react with nitrogen and oxygen atoms of zein molecules through coordination and electrostatic force. The CD spectra results suggested that PbS nanocrystals induced the conformational transition of protein from α-helix to β-sheet and then self-assembled into ring or toroid nanostructure. The quenching of zein fluorescence induced by PbS nanocrystals also showed the change in the chemical microenvironments of the fluorescent amino acid residues in the protein structure. The key step of this facile, biomimetic route was the formation of self-assembly nanostructure of zein, which could regulate the nucleation and growth of toroid-like PbS nanocrystals

  18. Decreased expression of heat shock proteins may lead to compromised wound healing in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Mohan, Gyanendra; Chaturvedi, Sunanda; Singh, Kiran

    2015-01-01

    Heat shock proteins (HSPs) are inducible stress proteins expressed in cells exposed to stress. HSPs promote wound healing by recruitment of dermal fibroblasts to the site of injury and bring about protein homeostasis. Diabetic wounds are hard to heal and inadequate HSPs may be important contributors in the etiology of diabetic foot ulcers (DFU). To analyze the differential expression of HSPs and their downstream molecules in human diabetic wounds compared to control wounds. Expressional levels of HSP27, HSP47 and HSP70 and their downstream molecules like TLR4, p38-MAPK were seen in biopsies from 101 human diabetic wounds compared to 8 control subjects without diabetes using RT-PCR, western blot and immunohistochemistry. Our study suggested a significant down regulation of HSP70, HSP47 and HSP27 (p value=diabetic wounds. Our study demonstrates that the down regulation of HSPs in diabetic wounds is associated with wound healing impairment in T2DM subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Energy Technology Data Exchange (ETDEWEB)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-13

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2 . Surprisingly, hcef2 was mapped to a nonsense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDHrelated CEF. We observed similar increases in CEF and H2O2 accumulation in other translation defective mutants, suggesting that loss of coordination in plastid protein levels lead to imbalances in the photosynthetic energy balance that leads to increased CEF. These results, together with a large body of previous observations, support a general model in which processes that imbalances in chloroplast energetics result in the production of H2O2 , which activates CEF, either as a redox signal or by inducing deficits in ATP levels.

  20. Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

    Science.gov (United States)

    Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

    2017-12-01

    Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

  1. Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia.

    Science.gov (United States)

    Le Sommer, Samantha; Morrice, Nicola; Pesaresi, Martina; Thompson, Dawn; Vickers, Mark A; Murray, Graeme I; Mody, Nimesh; Neel, Benjamin G; Bence, Kendra K; Wilson, Heather M; Delibegović, Mirela

    2018-01-01

    Protein tyrosine phosphatase PTP1B is a critical regulator of signaling pathways controlling metabolic homeostasis, cell proliferation, and immunity. In this study, we report that global or myeloid-specific deficiency of PTP1B in mice decreases lifespan. We demonstrate that myeloid-specific deficiency of PTP1B is sufficient to promote the development of acute myeloid leukemia. LysM-PTP1B -/- mice lacking PTP1B in the innate myeloid cell lineage displayed a dysregulation of bone marrow cells with a rapid decline in population at midlife and a concomitant increase in peripheral blood blast cells. This phenotype manifested further with extramedullary tumors, hepatic macrophage infiltration, and metabolic reprogramming, suggesting increased hepatic lipid metabolism prior to overt tumor development. Mechanistic investigations revealed an increase in anti-inflammatory M2 macrophage responses in liver and spleen, as associated with increased expression of arginase I and the cytokines IL10 and IL4. We also documented STAT3 hypersphosphorylation and signaling along with JAK-dependent upregulation of antiapoptotic proteins Bcl2 and BclXL. Our results establish a tumor suppressor role for PTP1B in the myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia. Significance: This study defines a tumor suppressor function for the protein tyrosine phosphatase PTP1B in myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia. Cancer Res; 78(1); 75-87. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Discovery of an Unexplored Protein Structural Scaffold of Serine Protease from Big Blue Octopus (Octopus cyanea): A New Prospective Lead Molecule.

    Science.gov (United States)

    Panda, Subhamay; Kumari, Leena

    2017-01-01

    Serine proteases are a group of enzymes that hydrolyses the peptide bonds in proteins. In mammals, these enzymes help in the regulation of several major physiological functions such as digestion, blood clotting, responses of immune system, reproductive functions and the complement system. Serine proteases obtained from the venom of Octopodidae family is a relatively unexplored area of research. In the present work, we tried to effectively utilize comparative composite molecular modeling technique. Our key aim was to propose the first molecular model structure of unexplored serine protease 5 derived from big blue octopus. The other objective of this study was to analyze the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the aid of different bioinformatic tools. In the present study, molecular model has been generated with the help of I-TASSER suite. Afterwards the refined structural model was validated with standard methods. For functional annotation of protein molecule we used Protein Information Resource (PIR) database. Serine protease 5 of big blue octopus was analyzed with different bioinformatical algorithms for the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) were determined using the COACH program. The molecular model data in cooperation to other pertinent post model analysis data put forward molecular insight to proteolytic activity of serine protease 5, which helps in the clear understanding of procoagulant and anticoagulant characteristics of this natural lead molecule. Our approach was to investigate the octopus

  3. Leading coordinate analysis of reaction pathways in proton chain transfer: Application to a two-proton transfer model for the green fluorescent protein

    International Nuclear Information System (INIS)

    Wang Sufan; Smith, Sean C.

    2006-01-01

    The 'leading coordinate' approach to computing an approximate reaction pathway, with subsequent determination of the true minimum energy profile, is applied to a two-proton chain transfer model based on the chromophore and its surrounding moieties within the green fluorescent protein (GFP). Using an ab initio quantum chemical method, a number of different relaxed energy profiles are found for several plausible guesses at leading coordinates. The results obtained for different trial leading coordinates are rationalized through the calculation of a two-dimensional relaxed potential energy surface (PES) for the system. Analysis of the 2-D relaxed PES reveals that two of the trial pathways are entirely spurious, while two others contain useful information and can be used to furnish starting points for successful saddle-point searches. Implications for selection of trial leading coordinates in this class of proton chain transfer reactions are discussed, and a simple diagnostic function is proposed for revealing whether or not a relaxed pathway based on a trial leading coordinate is likely to furnish useful information

  4. C-reactive protein testing in patients with acute rhinosinusitis leads to a reduction in antibiotic use

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars; Arranz, Javier

    2012-01-01

    OBJECTIVE: To evaluate the effect of C-reactive protein (CRP) testing on the antibiotic prescribing in patients with acute rhinosinusitis. METHODS: Audit-based study carried out in primary care centres in Spain. GPs registered episodes of rhinosinusitis during 3-week period before and after...... an intervention. Two types of intervention were considered: full intervention group (FIG) consisting in individual feedback based on results from the first registry, courses in rational antibiotic prescribing, guidelines, patient information leaflets, workshops on rapid tests and use of the CRP test. GPs...... in the partial intervention group (PIG) underwent all the above intervention except for the workshop and they did not have access to CRP. Multilevel logistic regression analysis was performed considering the prescription of antibiotics as the dependent variable. RESULTS: Two hundred and ten physicians were...

  5. Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon.

    Directory of Open Access Journals (Sweden)

    Natalia López-del Hoyo

    Full Text Available Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout and gain-of-function (transgenic overexpression mouse models of GCAP2. Rod synaptic ribbons in GCAPs-/- mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs-/- background (GCAP2 expression in the absence of endogenous GCAP1 had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of

  6. Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p53 and p21/WAF1 proteins in skin of mice

    International Nuclear Information System (INIS)

    Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul; Dhawan, Alok; Dwivedi, Premendra D.; Das, Mukul

    2009-01-01

    Patulin (PAT), a mycotoxin found in apples, grapes, oranges, pear and peaches, is a potent genotoxic compound. WHO has highlighted the need for the study of cutaneous toxicity of PAT as manual labour is employed during pre and post harvest stages, thereby causing direct exposure to skin. In the present study cutaneous toxicity of PAT was evaluated following topical application to Swiss Albino mice. Dermal exposure of PAT, to mice for 4 h resulted in a dose (40-160 μg/animal) and time (up to 6 h) dependent enhancement of ornithine decarboxylase (ODC), a marker enzyme of cell proliferation. The ODC activity was found to be normal after 12 and 24 h treatment of patulin. Topical application of PAT (160 μg/100 μl acetone) for 24-72 h caused (a) DNA damage in skin cells showing significant increase (34-63%) in olive tail moment, a parameter of Comet assay (b) significant G 1 and S-phase arrest along with induction of apoptosis (2.8-10 folds) as shown by annexin V and PI staining assay through flow cytometer. Moreover PAT leads to over expression of p 21/WAF1 (3.6-3.9 fold), pro apoptotic protein Bax (1.3-2.6) and tumor suppressor wild type p 53 (2.8-3.9 fold) protein. It was also shown that PAT induced apoptosis was mediated through mitochondrial intrinsic pathway as revealed through the release of cytochrome C protein in cytosol leading to enhancement of caspase-3 activity in skin cells of mice. These results suggest that PAT has a potential to induce DNA damage leading to p 53 mediated cell cycle arrest along with intrinsic pathway mediated apoptosis that may also be correlated with enhanced polyamine production as evident by induction of ODC activity, which may have dermal toxicological implications

  7. Ectopic expression of MPF2-like protein WSA206 leads to arrest in silique and seed development in heterologous host

    International Nuclear Information System (INIS)

    Khan, M.R.

    2016-01-01

    MPF2-like genes belonging to STMADS11 clade of MADS-box transcription factors are mostly involved in calyx inflation, floral reversion and fertility. However their role in fertility remained enigmatic. In this study we transformed WSA206 gene paralog - originated through genome duplication in a Solanaceous plant Withaniasomnifera - ectopically in a heterologous host Arabidopsis thaliana. Interesting phenotypes in floral organs and fruits were observed. Overexpression of WSA206 leads to arrest in silique development. The siliques were compressed and size was drastically reduced from 34mm to 3mm. Along with siliques, the seed development was also suppressed as revealed by shriveling of seeds and reduction in seed number. In extreme cases the siliques were devoid of any seeds. In cases where seeds developed, these were impaired in viability. Besides, the transgenic Arabidopsis also exhibited exorbitant growth of calyx to an extent that it resembled inflated calyx in Solanaceae. The calyx remained persistent and encapsulated the under-developed siliques containing non-viable seeds inside. Thus, fertility and sepal development are tightly coupled traits that are controlled by WSA206 paralog in heterologous system. (author)

  8. How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases or mutation (∼5% of SMA cases of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs, which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136 with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface.

  9. Nodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress

    Energy Technology Data Exchange (ETDEWEB)

    Meili, Nicole; Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)

    2016-06-01

    Nodularin is produced by the cyanobacterium Nodularia spumigena. It is of concern due to hepatotoxicity in humans and animals. Here we investigated unexplored molecular mechanisms by transcription analysis in human liver cells, focusing on induction of pro-inflammatory cytokines, the tumor necrosis factor α (TNF-α), endoplasmic reticulum (ER) stress and components of the activator protein-1 complex in human hepatoma cells (Huh7) exposed to non-cytotoxic (0.1 and 1 μM) and toxic concentrations (5 μM) for 24, 48, and 72 h. Transcripts of TNF-α and ER stress marker genes were strongly induced at 1 and 5 μM at all time-points. TNF-α led to induction of mitogen-activated protein kinases (MAPK), as demonstrated by induction of CJUN and CFOS, which form the AP-1 complex. Human primary liver cells reacted more sensitive than Huh7 cells. They showed higher cytotoxicity and induction of TNF-α and ER stress at 2.5 nM, while HepG2 cells were insensitive up to 10 μM due to low expression of organic anion transporting polypeptides. Furthermore, nodularin led to induction of TNF-α protein, and CCAAT/enhancer-binding protein-homologous (CHOP) protein. Our data indicate that nodularin induces inflammation and ER stress and leads to activation of MAPK in liver cells. All of these activated pathways, which were analysed here for the first time in detail, may contribute to the hepatotoxic, and tumorigenic action of nodularin. - Highlights: • Toxicity of nodularin and its mechanisms of action are poorly understood. • We investigated mechanisms of nodularin toxicity in human liver cell lines and human hepatocytes. • We identified several pathways involved in nodularin toxicity. • Nodularin induces TNF-α, MAPK pathway and ER stress • These activated pathways may contribute to the hepatotoxic and tumorigenic action of nodularin.

  10. Nodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress

    International Nuclear Information System (INIS)

    Meili, Nicole; Christen, Verena; Fent, Karl

    2016-01-01

    Nodularin is produced by the cyanobacterium Nodularia spumigena. It is of concern due to hepatotoxicity in humans and animals. Here we investigated unexplored molecular mechanisms by transcription analysis in human liver cells, focusing on induction of pro-inflammatory cytokines, the tumor necrosis factor α (TNF-α), endoplasmic reticulum (ER) stress and components of the activator protein-1 complex in human hepatoma cells (Huh7) exposed to non-cytotoxic (0.1 and 1 μM) and toxic concentrations (5 μM) for 24, 48, and 72 h. Transcripts of TNF-α and ER stress marker genes were strongly induced at 1 and 5 μM at all time-points. TNF-α led to induction of mitogen-activated protein kinases (MAPK), as demonstrated by induction of CJUN and CFOS, which form the AP-1 complex. Human primary liver cells reacted more sensitive than Huh7 cells. They showed higher cytotoxicity and induction of TNF-α and ER stress at 2.5 nM, while HepG2 cells were insensitive up to 10 μM due to low expression of organic anion transporting polypeptides. Furthermore, nodularin led to induction of TNF-α protein, and CCAAT/enhancer-binding protein-homologous (CHOP) protein. Our data indicate that nodularin induces inflammation and ER stress and leads to activation of MAPK in liver cells. All of these activated pathways, which were analysed here for the first time in detail, may contribute to the hepatotoxic, and tumorigenic action of nodularin. - Highlights: • Toxicity of nodularin and its mechanisms of action are poorly understood. • We investigated mechanisms of nodularin toxicity in human liver cell lines and human hepatocytes. • We identified several pathways involved in nodularin toxicity. • Nodularin induces TNF-α, MAPK pathway and ER stress • These activated pathways may contribute to the hepatotoxic and tumorigenic action of nodularin.

  11. Magnetic Particle-Based Immunoassay of Phosphorylated p53 Using Protein-Cage Templated Lead Phosphate and Carbon Nanospheres for Signal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Aiqiong; Bao, Yuanwu; Ge, Xiaoxiao; Shin, Yongsoon; Du, Dan; Lin, Yuehe

    2012-11-20

    Phosphorylated p53 at serin 15 (phospho-p53-15) is a potential biomarker of Gamma-radiation exposure. In this paper, we described a new magnetic particles (MPs)-based electrochemical immunoassay of human phospho-p53-15 using carbon nanospheres (CNS) and protein-cage templated lead phosphate nanoparticles for signal amplification. Greatly enhanced sensitivity was achieved by three aspects: 1) The protein-cage nanoparticle (PCN) and p53-15 signal antibody (p53-15 Ab2) are linked to CNS (PCNof each apoferritin; 3) MPs capture a large amount of primary antibodies. Using apoferritin templated metallic phosphate instead of enzyme as label has the advantage of eliminating the addition of mediator or immunoreagents and thus makes the immunoassay system simpler. The subsequent stripping voltammetric analysis of the released lead ions were detected on a disposable screen printed electrode. The response current was proportional to the phospho-p53-15 concentration in the range of 0.02 to 20 ng mL-1 with detection limit of 0.01 ng mL-1. This method shows a good stability, reproducibility and recovery.

  12. Receptor trafficking via the perinuclear recycling compartment accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase activation.

    Science.gov (United States)

    Toy-Miou-Leong, Mireille; Cortes, Catherine Llorens; Beaudet, Alain; Rostène, William; Forgez, Patricia

    2004-03-26

    Most G protein-coupled receptors are internalized after interaction with their respective ligand, a process that subsequently contributes to cell desensitization, receptor endocytosis, trafficking, and finally cell resensitization. Although cellular mechanisms leading to cell desensitization have been widely studied, those responsible for cell resensitization are still poorly understood. We examined here the traffic of the high affinity neurotensin receptor (NT1 receptor) following prolonged exposure to high agonist concentration. Fluorescence and confocal microscopy of Chinese hamster ovary, human neuroblastoma (CHP 212), and murine neuroblastoma (N1E-115) cells expressing green fluorescent protein-tagged NT1 receptor revealed that under prolonged treatment with saturating concentrations of neurotensin (NT) agonist, NT1 receptor and NT transiently accumulated in the perinuclear recycling compartment (PNRC). During this cellular event, cell surface receptors remained markedly depleted as detected by both confocal microscopy and (125)I-NT binding assays. In dividing cells, we observed that following prolonged NT agonist stimulation, NT1 receptors were removed from the PNRC, accumulated in dispersed vesicles inside the cytoplasm, and subsequently reappeared at the cell surface. This NT binding recovery allowed for constant cell sensitization and led to a chronic activation of mitogen-activated protein kinases p42 and p44. Under these conditions, the constant activation of NT1 receptor generates an oncogenic regulation. These observations support the potent role for neuropeptides, such as NT, in cancer progression.

  13. 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

  14. The rice dwarf virus P2 protein interacts with ent-kaurene oxidases in vivo, leading to reduced biosynthesis of gibberellins and rice dwarf symptoms.

    Science.gov (United States)

    Zhu, Shifeng; Gao, Feng; Cao, Xuesong; Chen, Mao; Ye, Gongyin; Wei, Chunhong; Li, Yi

    2005-12-01

    The mechanisms of viral diseases are a major focus of biology. Despite intensive investigations, how a plant virus interacts with host factors to cause diseases remains poorly understood. The Rice dwarf virus (RDV), a member of the genus Phytoreovirus, causes dwarfed growth phenotypes in infected rice (Oryza sativa) plants. The outer capsid protein P2 is essential during RDV infection of insects and thus influences transmission of RDV by the insect vector. However, its role during RDV infection within the rice host is unknown. By yeast two-hybrid and coimmunoprecipitation assays, we report that P2 of RDV interacts with ent-kaurene oxidases, which play a key role in the biosynthesis of plant growth hormones gibberellins, in infected plants. Furthermore, the expression of ent-kaurene oxidases was reduced in the infected plants. The level of endogenous GA1 (a major active gibberellin in rice vegetative tissues) in the RDV-infected plants was lower than that in healthy plants. Exogenous application of GA3 to RDV-infected rice plants restored the normal growth phenotypes. These results provide evidence that the P2 protein of RDV interferes with the function of a cellular factor, through direct physical interactions, that is important for the biosynthesis of a growth hormone leading to symptom expression. In addition, the interaction between P2 and rice ent-kaurene oxidase-like proteins may decrease phytoalexin biosynthesis and make plants more competent for virus replication. Moreover, P2 may provide a novel tool to investigate the regulation of GA metabolism for plant growth and development.

  15. The Rice Dwarf Virus P2 Protein Interacts with ent-Kaurene Oxidases in Vivo, Leading to Reduced Biosynthesis of Gibberellins and Rice Dwarf Symptoms1

    Science.gov (United States)

    Zhu, Shifeng; Gao, Feng; Cao, Xuesong; Chen, Mao; Ye, Gongyin; Wei, Chunhong; Li, Yi

    2005-01-01

    The mechanisms of viral diseases are a major focus of biology. Despite intensive investigations, how a plant virus interacts with host factors to cause diseases remains poorly understood. The Rice dwarf virus (RDV), a member of the genus Phytoreovirus, causes dwarfed growth phenotypes in infected rice (Oryza sativa) plants. The outer capsid protein P2 is essential during RDV infection of insects and thus influences transmission of RDV by the insect vector. However, its role during RDV infection within the rice host is unknown. By yeast two-hybrid and coimmunoprecipitation assays, we report that P2 of RDV interacts with ent-kaurene oxidases, which play a key role in the biosynthesis of plant growth hormones gibberellins, in infected plants. Furthermore, the expression of ent-kaurene oxidases was reduced in the infected plants. The level of endogenous GA1 (a major active gibberellin in rice vegetative tissues) in the RDV-infected plants was lower than that in healthy plants. Exogenous application of GA3 to RDV-infected rice plants restored the normal growth phenotypes. These results provide evidence that the P2 protein of RDV interferes with the function of a cellular factor, through direct physical interactions, that is important for the biosynthesis of a growth hormone leading to symptom expression. In addition, the interaction between P2 and rice ent-kaurene oxidase-like proteins may decrease phytoalexin biosynthesis and make plants more competent for virus replication. Moreover, P2 may provide a novel tool to investigate the regulation of GA metabolism for plant growth and development. PMID:16299167

  16. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction.

    Science.gov (United States)

    Tomàs, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomàs, Marta; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M 1 , M 2 and M 4 ), adenosine receptors (AR; A 1 and A 2A ) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A 1 , M 1 and TrkB operate mainly by stimulating PKC whereas A 2A , M 2 and M 4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and

  17. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Josep M. Tomàs

    2017-08-01

    Full Text Available Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh receptors (subtypes mAChR; M1, M2 and M4, adenosine receptors (AR; A1 and A2A and the tropomyosin-related kinase B receptor (TrkB, among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC, to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ. This hypothesis is supported by: (i the tonic effect (shown by using selective inhibitors of several membrane receptors that accelerates axon loss between postnatal days P5–P9; (ii the synergistic, antagonic and modulatory effects (shown by paired inhibition of the receptors on axonal loss; (iii the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various

  18. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

    LENUS (Irish Health Repository)

    Thewes, Verena

    2010-05-11

    Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

  19. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells

    International Nuclear Information System (INIS)

    Thewes, Verena; Orso, Francesca; Jäger, Richard; Eckert, Dawid; Schäfer, Sabine; Kirfel, Gregor; Garbe, Stephan; Taverna, Daniela; Schorle, Hubert

    2010-01-01

    Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference

  20. Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells.

    Directory of Open Access Journals (Sweden)

    Udaya S Rangaswamy

    2014-01-01

    Full Text Available Reactivation of the gammaherpesviruses Epstein-Barr virus (EBV, Kaposi's sarcoma-associated herpesvirus (KSHV and murine gammaherpesvirus 68 (MHV68 from latently infected B cells has been linked to plasma cell differentiation. We have previously shown that the MHV68 M2 protein is important for virus reactivation from B cells and, when expressed alone in primary murine B cells, can drive B cell differentiation towards a pre-plasma cell phenotype. In addition, expression of M2 in primary murine B cells leads to secretion of high levels of IL-10 along with enhanced proliferation and survival. Furthermore, the absence of M2 in vivo leads to a defect in the appearance of MHV68 infected plasma cells in the spleen at the peak of MHV68 latency. Here, employing an inducible B cell expression system, we have determined that M2 activates the NFAT pathway in a Src kinase-dependent manner--leading to induction of the plasma cell-associated transcription factor, Interferon Regulatory Factor-4 (IRF4. Furthermore, we show that expression of IRF4 alone in a B cell line up-regulates IL-10 expression in culture supernatants, revealing a novel role for IRF4 in B cell induced IL-10. Consistent with the latter observation, we show that IRF4 can regulate the IL-10 promoter in B cells. In primary murine B cells, addition of cyclosporine (CsA resulted in a significant decrease in M2-induced IL-10 levels as well as IRF4 expression, emphasizing the importance of the NFAT pathway in M2- -mediated induction of IL-10. Together, these studies argue in favor of a model wherein M2 activation of the NFAT pathway initiates events leading to increased levels of IRF4--a key player in plasma cell differentiation--which in turn triggers IL-10 expression. In the context of previous findings, the data presented here provides insights into how M2 facilitates plasma cell differentiation and subsequent virus reactivation.

  1. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Cross-linking of cell surface amyloid precursor protein leads to increased β-amyloid peptide production in hippocampal neurons: implications for Alzheimer's disease.

    Science.gov (United States)

    Lefort, Roger; Pozueta, Julio; Shelanski, Michael

    2012-08-01

    The accumulation of the β-amyloid peptide (Aβ) in Alzheimer's disease (AD) is thought to play a causative role in triggering synaptic dysfunction in neurons, leading to their eventual demise through apoptosis. Aβ is produced and secreted upon sequential cleavage of the amyloid precursor protein (APP) by β-secretases and γ-secretases. However, while Aβ levels have been shown to be increased in the brains of AD patients, little is known about how the cleavage of APP and the subsequent generation of Aβ is influenced, or whether the cleavage process changes over time. It has been proposed that Aβ can bind APP and promote amyloidogenic processing of APP, further enhancing Aβ production. Proof of this idea has remained elusive because a clear mechanism has not been identified, and the promiscuous nature of Aβ binding complicates the task of demonstrating the idea. To work around these problems, we used an antibody-mediated approach to bind and cross-link cell-surface APP in cultured rat primary hippocampal neurons. Here we show that cross-linking of APP is sufficient to raise the levels of Aβ in viable neurons with a concomitant increase in the levels of the β-secretase BACE1. This appears to occur as a result of a sorting defect that stems from the caspase-3-mediated inactivation of a key sorting adaptor protein, namely GGA3, which prevents the lysosomal degradation of BACE1. Together, our data suggest the occurrence of a positive pathogenic feedback loop involving Aβ and APP in affected neurons possibly allowing Aβ to spread to nearby healthy neurons.

  3. Lead poisoning

    Science.gov (United States)

    ... drinking water in homes containing pipes that were connected with lead solder . Although new building codes require ... lead in their bodies when they put lead objects in their mouths, especially if they swallow those ...

  4. 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 ...

  5. Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: correlation with development of hypercholesterolemia.

    Science.gov (United States)

    Kojima, Misaki; Degawa, Masakuni

    2006-01-01

    Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats. Copyright (c) 2006 John Wiley & Sons, Ltd.

  6. Effect of lead on nucleic acid and protein contents of rice (Oryza sativa L. ) seedlings and its interaction with IAA and GA/sub 3/ in different plant systems

    Energy Technology Data Exchange (ETDEWEB)

    Maitra, P.; Mukherh, S.

    1979-09-01

    Activity of lead acetate, (CH/sub 3/COO)/sub 2/Pb, 3 H/sub 2/O, was studied in germinating rice seedlings with respect to RNA, DNA and alkali soluble protein contents. RNA, DNA and protein contents greatly reduced both in embryo and endosperm with increasing concentrations of lead and with concomitant increase in amino acid content in embryo. When IAA was supplied in combination with lead acetate, variable amounts of relief of elongation inhibition of wheat coleoptile sections were noticed. With GA/sub 3/, however, lead-induced inhibition of either lettuce (Lactuca sativa L.) hypocotyl elongation or ..cap alpha..-amylase production in rice half seeds was largely overcome.

  7. Lead poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Beijers, J A

    1952-01-01

    Three cases of acute lead poisoning of cattle herds via ingestion are reported, and reference is made to several other incidents of lead in both humans and animals. The quantity of lead which was found in the livers of the dead cows varied from 6.5 to 19 mg/kg, while 1160 mg/kg of lead in the liver was found for a young cow which was poisoned experimentally with 5 gms of lead acetate per day; hence, there appears to be great variability in the amounts deposited that can lead to intoxication and death. No evidence was found for a lead seam around the teeth, prophyrinuria, or basophil granules in the erythrocytes during acute or chronic lead poisoning of cattle or horses examined. Reference is made to attempts of finding the boundary line between increased lead absorption and lead intoxication in humans, and an examination of 60 laborers in an offset-printing office containing a great deal of inhalable lead (0.16 to 1.9 mg/cu m air) is reviewed. Physical deviation, basophylic granulation of erythrocytes, increased lead content of the urine, and porphyrinuria only indicate an increased absorption of lead; the use of the term intoxication is justified if, in addition, there are complaints of lack of appetite, constipation, fatigue, abdominal pain, and emaciation.

  8. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications.

    Science.gov (United States)

    Imaduwage, Kasun P; Go, Eden P; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have K i values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods. Graphical Abstract ᅟ.

  9. The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase

    Directory of Open Access Journals (Sweden)

    Famin O.

    2003-03-01

    Full Text Available Ferriprotoporphyrin IX (FPIX is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins. Parasite enzymes such as aldolase, pyrimidine nucleoside monophosphate kinase and pyrimidine 5'- nucleotidase were inhibited by FPIX in vitro, but only the activity of 6-phosphogluconate dehydrogenase was reduced significantly in cells after drug treatment. Additional proteins were extracted from parasite cytosol by their ability to bind FPIX. Sequencing of these proteins identified heat shock proteins 90 and 70, enolase, elongation factor 1-α, phoshoglycerate kinase, glyceraldehyde 3- phosphate dehydrogenase, L-lactate dehydrogenase and gametocytogenesis onset-specific protein. The possible involvement of these proteins in the antimalarial mode of action of chloroquine is discussed. It is concluded that drug-induced binding of FPIX to parasite glycolytic enzymes could underlie the demonstrable inhibition of glycolysis by chloroquine. The inhibition of 6- phosphogluconate dehydrogenase could explain the reduction of the activity of the hexose monophosphate shunt by the drug. Inhibition of both processes is deleterious to parasite survival. Binding of FPIX to other proteins is probably inconsequential to the rapid killing of the parasite by chloroquine.

  10. Lead Toxicity

    Science.gov (United States)

    ... o Do not use glazed ceramics, home remedies, cosmetics, or leaded-crystal glassware unless you know that they are lead safe. o If you live near an industry, mine, or waste site that may have contaminated ...

  11. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  12. Lead Test

    Science.gov (United States)

    ... to do renovation and repair projects using lead-safe work practices to avoid creating more lead dust or ... in a dangerous area? Yes. If you are working in a potentially harmful environment with exposure to lead dust or fumes: Wash ...

  13. Leading survey and research report for fiscal 1999. New technology based on functions involved in intracellular protein transport; 1999 nendo saibonai tanpakushitsu yuso kino riyo gijutsu kenkyu hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    An intercellular transport technology (artificial manipulation of an intracellular protein transport system in eucaryotes) is studied for the accumulation of cytotoxic proteins, whose expression has so far been difficult, and activated proteins, which have avoided decomposition, in appropriate intracellular minute organs. The aim is to construct a system to allow foreign proteins high in productivity and quality to express themselves for production in eucaryotes. Basic surveys were conducted of the intracellular biological functions of single-membrane organelles (endoplasmic reticulum, peroxisome, vacuole/lysosome, and Golgi body), the molecular mechanism of protein transport to each organelle, and protein activation and quality control, and element technologies were extracted. For the development of novel pharmaceuticals making use of the intracellular protein transport technology, an activated protein production system was built and a search was made for transport activity impeding substances. Research tasks relative to the development of the new technologies were isolated, such as the visualization of intercellular transport. A survey was made of the market for pharmaceuticals, cosmetics, enzymes, and visualizing equipment (fluorescence microscope provided with new functions), etc. (NEDO)

  14. The helicase, DDX3X, interacts with poly(A)-binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading.

    Science.gov (United States)

    Copsey, Alice C; Cooper, Simon; Parker, Robert; Lineham, Ella; Lapworth, Cuzack; Jallad, Deema; Sweet, Steve; Morley, Simon J

    2017-08-30

    DDX3X, a helicase, can interact directly with mRNA and translation initiation factors, regulating the selective translation of mRNAs that contain a structured 5' untranslated region. This activity modulates the expression of mRNAs controlling cell cycle progression and mRNAs regulating actin dynamics, contributing to cell adhesion and motility. Previously, we have shown that ribosomes and translation initiation factors localise to the leading edge of migrating fibroblasts in loci enriched with actively translating ribosomes, thereby promoting steady-state levels of ArpC2 and Rac1 proteins at the leading edge of cells during spreading. As DDX3X can regulate Rac1 levels, cell motility and metastasis, we have examined DDX3X protein interactions and localisation using many complementary approaches. We now show that DDX3X can physically interact and co-localise with poly(A)-binding protein 1 and caprin-1 at the leading edge of spreading cells. Furthermore, as depletion of DDX3X leads to decreased cell motility, this provides a functional link between DDX3X, caprin-1 and initiation factors at the leading edge of migrating cells to promote cell migration and spreading. © 2017 The Author(s).

  15. Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle

    International Nuclear Information System (INIS)

    Nguyen, Hau; Mudryj, Maria; Guadalupe, Moraima; Dandekar, Satya

    2003-01-01

    Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G 0 /G 1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor

  16. Leading Democratically

    Science.gov (United States)

    Brookfield, Stephen

    2010-01-01

    Democracy is the most venerated of American ideas, the one for which wars are fought and people die. So most people would probably agree that leaders should be able to lead well in a democratic society. Yet, genuinely democratic leadership is a relative rarity. Leading democratically means viewing leadership as a function or process, rather than…

  17. A nonadaptive origin of a beneficial trait: in silico selection for free energy of folding leads to the neutral emergence of mutational robustness in single domain proteins.

    Science.gov (United States)

    Pagan, Rafael F; Massey, Steven E

    2014-02-01

    Proteins are regarded as being robust to the deleterious effects of mutations. Here, the neutral emergence of mutational robustness in a population of single domain proteins is explored using computer simulations. A pairwise contact model was used to calculate the ΔG of folding (ΔG folding) using the three dimensional protein structure of leech eglin C. A random amino acid sequence with low mutational robustness, defined as the average ΔΔG resulting from a point mutation (ΔΔG average), was threaded onto the structure. A population of 1,000 threaded sequences was evolved under selection for stability, using an upper and lower energy threshold. Under these conditions, mutational robustness increased over time in the most common sequence in the population. In contrast, when the wild type sequence was used it did not show an increase in robustness. This implies that the emergence of mutational robustness is sequence specific and that wild type sequences may be close to maximal robustness. In addition, an inverse relationship between ∆∆G average and protein stability is shown, resulting partly from a larger average effect of point mutations in more stable proteins. The emergence of mutational robustness was also observed in the Escherichia coli colE1 Rop and human CD59 proteins, implying that the property may be common in single domain proteins under certain simulation conditions. The results indicate that at least a portion of mutational robustness in small globular proteins might have arisen by a process of neutral emergence, and could be an example of a beneficial trait that has not been directly selected for, termed a "pseudaptation."

  18. Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

    Science.gov (United States)

    Makrythanasis, Periklis; Bernard, Pascal; Kurosaka, Hiroshi; Vannier, Anne; Thauvin-Robinet, Christel; Borel, Christelle; Mazaud-Guittot, Séverine; Rolland, Antoine; Desdoits-Lethimonier, Christèle; Guipponi, Michel; Zimmermann, Céline; Stévant, Isabelle; Kuhne, Françoise; Conne, Béatrice; Santoni, Federico; Lambert, Sandy; Huet, Frederic; Mugneret, Francine; Jaruzelska, Jadwiga; Faivre, Laurence; Wilhelm, Dagmar; Jégou, Bernard; Trainor, Paul A.; Resh, Marilyn D.; Antonarakis, Stylianos E.; Nef, Serge

    2014-01-01

    The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development. PMID:24784881

  19. Leading change.

    Science.gov (United States)

    2017-02-27

    In response to feedback from nursing, midwifery and other care staff who wanted to understand better how the Leading Change, Adding Value framework applies to them, NHS England has updated its webpage to include practice examples.

  20. Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction

    International Nuclear Information System (INIS)

    Lehtivarjo, Juuso; Tuppurainen, Kari; Hassinen, Tommi; Laatikainen, Reino; Peräkylä, Mikael

    2012-01-01

    While chemical shifts are invaluable for obtaining structural information from proteins, they also offer one of the rare ways to obtain information about protein dynamics. A necessary tool in transforming chemical shifts into structural and dynamic information is chemical shift prediction. In our previous work we developed a method for 4D prediction of protein 1 H chemical shifts in which molecular motions, the 4th dimension, were modeled using molecular dynamics (MD) simulations. Although the approach clearly improved the prediction, the X-ray structures and single NMR conformers used in the model cannot be considered fully realistic models of protein in solution. In this work, NMR ensembles (NMRE) were used to expand the conformational space of proteins (e.g. side chains, flexible loops, termini), followed by MD simulations for each conformer to map the local fluctuations. Compared with the non-dynamic model, the NMRE+MD model gave 6–17% lower root-mean-square (RMS) errors for different backbone nuclei. The improved prediction indicates that NMR ensembles with MD simulations can be used to obtain a more realistic picture of protein structures in solutions and moreover underlines the importance of short and long time-scale dynamics for the prediction. The RMS errors of the NMRE+MD model were 0.24, 0.43, 0.98, 1.03, 1.16 and 2.39 ppm for 1 Hα, 1 HN, 13 Cα, 13 Cβ, 13 CO and backbone 15 N chemical shifts, respectively. The model is implemented in the prediction program 4DSPOT, available at http://www.uef.fi/4dspothttp://www.uef.fi/4dspot.

  1. Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction

    Energy Technology Data Exchange (ETDEWEB)

    Lehtivarjo, Juuso, E-mail: juuso.lehtivarjo@uef.fi; Tuppurainen, Kari; Hassinen, Tommi; Laatikainen, Reino [University of Eastern Finland, School of Pharmacy (Finland); Peraekylae, Mikael [University of Eastern Finland, Institute of Biomedicine (Finland)

    2012-03-15

    While chemical shifts are invaluable for obtaining structural information from proteins, they also offer one of the rare ways to obtain information about protein dynamics. A necessary tool in transforming chemical shifts into structural and dynamic information is chemical shift prediction. In our previous work we developed a method for 4D prediction of protein {sup 1}H chemical shifts in which molecular motions, the 4th dimension, were modeled using molecular dynamics (MD) simulations. Although the approach clearly improved the prediction, the X-ray structures and single NMR conformers used in the model cannot be considered fully realistic models of protein in solution. In this work, NMR ensembles (NMRE) were used to expand the conformational space of proteins (e.g. side chains, flexible loops, termini), followed by MD simulations for each conformer to map the local fluctuations. Compared with the non-dynamic model, the NMRE+MD model gave 6-17% lower root-mean-square (RMS) errors for different backbone nuclei. The improved prediction indicates that NMR ensembles with MD simulations can be used to obtain a more realistic picture of protein structures in solutions and moreover underlines the importance of short and long time-scale dynamics for the prediction. The RMS errors of the NMRE+MD model were 0.24, 0.43, 0.98, 1.03, 1.16 and 2.39 ppm for {sup 1}H{alpha}, {sup 1}HN, {sup 13}C{alpha}, {sup 13}C{beta}, {sup 13}CO and backbone {sup 15}N chemical shifts, respectively. The model is implemented in the prediction program 4DSPOT, available at http://www.uef.fi/4dspothttp://www.uef.fi/4dspot.

  2. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  3. 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.

  4. Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality

    DEFF Research Database (Denmark)

    Buchou, Thierry; Vernet, Muriel; Blond, Olivier

    2003-01-01

    in mice leads to postimplantation lethality. Mutant embryos were reduced in size at embryonic day 6.5 (E6.5). They did not exhibit signs of apoptosis but did show reduced cell proliferation. Mutant embryos were resorbed at E7.5. In vitro, CK2beta(-/-) morula development stopped after the blastocyst stage...

  5. Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

    Science.gov (United States)

    Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

    2014-01-01

    The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683

  6. 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...

  7. Certification of the content (mass fractions) of arsenic, cadmium, copper, cobalt, manganese, lead, selenium and zinc in a single-cell protein. CRM no. 274

    Energy Technology Data Exchange (ETDEWEB)

    Griepink, B

    1987-01-01

    This report describes the preparation of a single cell protein as a reference material. Homogeneity and stability of the material are studied. The applied methods for the determination of concentrations of As, Cd, Cu, Co, Mn, Pb, Se, and Zn are presented, the contents of which are resp.: 0.1, 0.03, 0.04, 13, 52, 0.04, 1 and 43 ..mu..g/g. With 5 graphs, 55 tabs.

  8. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  9. Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to Elimination of Germline-Specific DNA

    Directory of Open Access Journals (Sweden)

    Dominique I. Furrer

    2017-07-01

    Full Text Available Piwi proteins and piRNAs protect eukaryotic germlines against the spread of transposons. During development in the ciliate Paramecium, two Piwi-dependent sRNA classes are involved in the elimination of transposons and transposon-derived DNA: scan RNAs (scnRNAs, associated with Ptiwi01 and Ptiwi09, and iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs derive from the maternal genome and initiate DNA elimination during development, whereas iesRNAs continue DNA targeting until the removal process is complete. Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like proteins and bind Piwi proteins in a mutually exclusive manner, suggesting separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is transcribed from the developing nucleus and that its transcription depends on prior DNA excision, suggesting a mechanism of gene expression control triggered by the removal of short DNA segments interrupting the gene.

  10. Chronologically scheduled snacking with high-protein products within the habitual diet in type-2 diabetes patients leads to a fat mass loss: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Martínez J Alfredo

    2011-07-01

    Full Text Available Abstract Background Obesity is the most relevant overnutrition disease worldwide and is associated to different metabolic disorders such as insulin resistance and type-2 diabetes. Low glycemic load foods and diets and moderately high protein intake have been shown to reduce body weight and fat mass, exerting also beneficial effects on LDL-cholesterol, triglyceride concentrations, postprandial glucose curve and HDL-cholesterol levels. The present study aimed at studying the potential functionality of a series of low glycemic index products with moderately high protein content, as possible coadjuvants in the control of type-2 diabetes and weight management following a chronologically planned snacking offer (morning and afternoon. Methods The current trial followed a single group, sequential, longitudinal design, with two consecutive periods of 4 weeks each. A total of 17 volunteers participated in the study. The first period was a free living period, with volunteers' habitual ad libitum dietary pattern, while the second period was a free-living period with structured meal replacements at breakfast, morning snack and afternoon snack, which were exchanged by specific products with moderately high protein content and controlled low glycemic index, following a scheduled temporal consumption. Blood extractions were performed at the beginning and at the end of each period (free-living and intervention. Parameters analysed were: fasting glucose, insulin, glycosylated hemoglobin, total-, HDL- and LDL-cholesterol, triglyceride, C - reactive protein and Homocysteine concentrations. Postprandial glucose and insulin were also measured. Anthropometrical parameters were monitored each 2 weeks during the whole study. Results A modest but significant (p = 0.002 reduction on body weight (1 kg was observed during the intervention period, mainly due to the fat mass loss (0.8 kg, p = 0.02. This weight reduction was observed without apparently associated changes in

  11. Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

    Science.gov (United States)

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

    2018-01-01

    We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

  12. A vaccinia virus recombinant transcribing an alphavirus replicon and expressing alphavirus structural proteins leads to packaging of alphavirus infectious single cycle particles.

    Directory of Open Access Journals (Sweden)

    Juana M Sánchez-Puig

    Full Text Available Poxviruses and Alphaviruses constitute two promising viral vectors that have been used extensively as expression systems, or as vehicles for vaccine purposes. Poxviruses, like vaccinia virus (VV are well-established vaccine vectors having large insertion capacity, excellent stability, and ease of administration. In turn, replicons derived from Alphaviruses like Semliki Forest virus (SFV are potent protein expression and immunization vectors but stocks are difficult to produce and maintain. In an attempt to demonstrate the use of a Poxvirus as a means for the delivery of small vaccine vectors, we have constructed and characterized VV/SFV hybrid vectors. A SFV replicon cDNA was inserted in the VV genome and placed under the control of a VV early promoter. The replicon, transcribed from the VV genome as an early transcript, was functional, and thus capable of initiating its own replication and transcription. Further, we constructed a VV recombinant additionally expressing the SFV structural proteins under the control of a vaccinia synthetic early/late promoter. Infection with this recombinant produced concurrent transcription of the replicon and expression of SFV structural proteins, and led to the generation of replicon-containing SFV particles that were released to the medium and were able to infect additional cells. This combined VV/SFV system in a single virus allows the use of VV as a SFV delivery vehicle in vivo. The combination of two vectors, and the possibility of generating in vivo single-cycle, replicon containing alphavirus particles, may open new strategies in vaccine development or in the design of oncolytic viruses.

  13. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPRMT and increased resistance to oxidative stress in primary cultures of fibroblasts

    Directory of Open Access Journals (Sweden)

    Gavin Pharaoh

    2016-08-01

    Full Text Available Mice deficient in the electron transport chain (ETC complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPRMT and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPRMT in response to reduced cytochrome c oxidase activity in Surf1−/− mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1−/− mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1−/− mice have increased expression of UPRMT components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1−/− mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1−/− fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1−/− fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPRMT in cell survival.

  14. A vaccinia virus recombinant transcribing an alphavirus replicon and expressing alphavirus structural proteins leads to packaging of alphavirus infectious single cycle particles.

    Science.gov (United States)

    Sánchez-Puig, Juana M; Lorenzo, María M; Blasco, Rafael

    2013-01-01

    Poxviruses and Alphaviruses constitute two promising viral vectors that have been used extensively as expression systems, or as vehicles for vaccine purposes. Poxviruses, like vaccinia virus (VV) are well-established vaccine vectors having large insertion capacity, excellent stability, and ease of administration. In turn, replicons derived from Alphaviruses like Semliki Forest virus (SFV) are potent protein expression and immunization vectors but stocks are difficult to produce and maintain. In an attempt to demonstrate the use of a Poxvirus as a means for the delivery of small vaccine vectors, we have constructed and characterized VV/SFV hybrid vectors. A SFV replicon cDNA was inserted in the VV genome and placed under the control of a VV early promoter. The replicon, transcribed from the VV genome as an early transcript, was functional, and thus capable of initiating its own replication and transcription. Further, we constructed a VV recombinant additionally expressing the SFV structural proteins under the control of a vaccinia synthetic early/late promoter. Infection with this recombinant produced concurrent transcription of the replicon and expression of SFV structural proteins, and led to the generation of replicon-containing SFV particles that were released to the medium and were able to infect additional cells. This combined VV/SFV system in a single virus allows the use of VV as a SFV delivery vehicle in vivo. The combination of two vectors, and the possibility of generating in vivo single-cycle, replicon containing alphavirus particles, may open new strategies in vaccine development or in the design of oncolytic viruses.

  15. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  16. Hepatitis C virus nonstructural protein 5A favors upregulation of gluconeogenic and lipogenic gene expression leading towards insulin resistance: a metabolic syndrome.

    Science.gov (United States)

    Parvaiz, Fahed; Manzoor, Sobia; Iqbal, Jawed; McRae, Steven; Javed, Farrakh; Ahmed, Qazi Laeeque; Waris, Gulam

    2014-05-01

    Chronic hepatitis C is a lethal blood-borne infection often associated with a number of pathologies such as insulin resistance and other metabolic abnormalities. Insulin is a key hormone that regulates the expression of metabolic pathways and favors homeostasis. In this study, we demonstrated the molecular mechanism of hepatitis C virus (HCV) nonstructural protein 5A (NS5A)-induced metabolic dysregulation. We showed that transient expression of HCV NS5A in human hepatoma cells increased lipid droplet formation through enhanced lipogenesis. We also showed increased transcriptional expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and diacylglycerol acyltransferase-1 (DGAT-1) in NS5A-expressing cells. On the other hand, there was significantly reduced transcriptional expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferator-activated receptor γ (PPARγ) in cells expressing HCV NS5A. Furthermore, increased gluconeogenic gene expression was observed in HCV-NS5A-expressing cells. In addition, it was also shown that HCV-NS5A-expressing hepatoma cells show serine phosphorylation of IRS-1, thereby hampering metabolic activity and contributing to insulin resistance. Therefore, this study reveals that HCV NS5A is involved in enhanced gluconeogenic and lipogenic gene expression, which triggers metabolic abnormality and impairs insulin signaling pathway.

  17. Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro.

    Science.gov (United States)

    Meller, R; Schindler, C K; Chu, X P; Xiong, Z G; Cameron, J A; Simon, R P; Henshall, D C

    2003-05-01

    Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNQX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-Xl after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.

  18. Degradation of the HilC and HilD regulator proteins by ATP-dependent Lon protease leads to downregulation of Salmonella pathogenicity island 1 gene expression.

    Science.gov (United States)

    Takaya, Akiko; Kubota, Yohsuke; Isogai, Emiko; Yamamoto, Tomoko

    2005-02-01

    Salmonella pathogenicity island 1 (SPI1) enables infecting Salmonella to cross the small intestinal barrier and to escape phagocytosis by inducing apoptosis. Several environmental signals and transcriptional regulators modulate the expression of hilA, which encodes a protein playing a central role in the regulatory hierarchy of SPI1 gene expression. We have previously shown that Lon, a stress-induced ATP-dependent protease, is a negative regulator of hilA, suggesting that it targets factors required for activating hilA expression. To elucidate the mechanisms by which Lon protease negatively regulates SPI1 transcription, we looked for its substrate proteins. We found that HilC and HilD, which are positive regulators of hilA expression, accumulate in Lon-depleted cells, and that the enhancement of SPI1 expression that occurs in a lon-disrupted mutant is not observed in the lon hilC hilD triple null mutant. Furthermore, we demonstrated that the half-lives of HilC and HilD are, respectively, about 12 times and three times longer in the Lon-depleted mutant, than in the Lon+ cells, suggesting that Lon targets both of HilC and HilD. In view of these findings, we suggest that the regulation of SPI1 expression is negatively controlled through degradation of the HilC and HilD transcriptional regulators by Lon.

  19. Transfer of the human NKG2D ligands UL16 binding proteins (ULBP) 1-3 is related to lytic granule release and leads to ligand retransfer and killing of ULBP-recipient natural killer cells.

    Science.gov (United States)

    López-Cobo, Sheila; Romera-Cárdenas, Gema; García-Cuesta, Eva M; Reyburn, Hugh T; Valés-Gómez, Mar

    2015-09-01

    After immune interactions, membrane fragments can be transferred between cells. This fast transfer of molecules is transient and shows selectivity for certain proteins; however, the constraints underlying acquisition of a protein are unknown. To characterize the mechanism and functional consequences of this process in natural killer (NK) cells, we have compared the transfer of different NKG2D ligands. We show that human NKG2D ligands can be acquired by NK cells with different efficiencies. The main findings are that NKG2D ligand transfer is related to immune activation and receptor-ligand interaction and that NK cells acquire these proteins during interactions with target cells that lead to degranulation. Our results further demonstrate that NK cells that have acquired NKG2D ligands can stimulate activation of autologous NK cells. Surprisingly, NK cells can also re-transfer the acquired molecule to autologous effector cells during this immune recognition that leads to their death. These data demonstrate that transfer of molecules occurs as a consequence of immune recognition and imply that this process might play a role in homeostatic tuning-down of the immune response or be used as marker of interaction. © 2015 John Wiley & Sons Ltd.

  20. Yield, SDG lignan, cadmium, lead, oil and protein contents of linseed (Linum usitatissimum L. cultivated in trials and at different farm conditions in the south-western part of Finland

    Directory of Open Access Journals (Sweden)

    Marketta Saastamoinen

    2013-06-01

    Full Text Available Linseed varieties were studied in variety trials and under farm conditions in south-western Finland in the years 2007−2010. The variation in yield, oil, protein, SDG lignan, cadmium and lead contents were studied in 8 oil and 2 fibre linseed varieties. Genotypic, environmental and genotype x environment interaction variance estimates were calculated. Fibre varieties ‘Belinka’ and ‘Martta’ had higher protein and lower oil contents than oil linseed varieties.The SDG lignan contents of linseed varieties varied between 3635−9560 mg kg-1. Rather high genotypic variance was found in yield, oil, protein and SDG lignan contents. Variety ‘Laser’ had lower SDG lignan content. ‘Abacus’, ‘Helmi’ and ‘Martta’ had the highest SDG lignan contents. Variation in cadmium and lead contents were caused by environmental effects. The highest cadmium contents, 0.82−1.69 mg kg-1, were found in soils fertilized by wastewater sludge about 20 years ago and at fields with low bottom soil pH (4.1−4.5.

  1. Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Moesgaard, S. G.

    2014-01-01

    not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine...... was significantly different in obese pigs (three up-regulated, six down-regulated). Of 33 genes in adipose tissues, obesity was associated with changed expression of 12 genes in the visceral adipose tissue (VAT) (three up-regulated), 11 in the abdominal retroperitoneal adipose tissue (RPAT) (seven of these up......-regulated) and eight in the subcutaneous adipose tissue (SAT) from the neck (five of which were up-regulated). Obesity-associated expression changes were observed for three genes in all adipose tissues, namely chemokine (C-C motif) ligand 3-like 1 (up-regulated), CD200 molecule (down-regulated) and interleukin 1...

  2. Blood-flow restricted training leads to myocelullar macrophage infiltration and upregulation of heat-shock proteins, but no apparent muscle damage

    DEFF Research Database (Denmark)

    Nielsen, Jakob L; Aagaard, Per; Prokhorova, Tatyana A

    2017-01-01

    Previous studies indicate that low-load muscle contractions performed under local blood-flow restriction (BFR) may initially induce muscle damage and stress. However, whether these factors are evoked with longitudinal BFR training remains unexplored at the myocellular level. Two distinct study...... into the intervention (Mid8) and 3 and 10 days after training cessation (Post3,Post10) to examine macrophage (M1/M2) content as well as heat-shock protein (HSP27/70) and tenascin-C expression. Blood samples (1 wk) were collected before and after (0.1-24 h) the first and last training session to examine markers...... of muscle damage (CK), oxidative stress (TAC,GSH) and inflammation (MCP1,IL-6,TNFa). M1-macrophage content increased 108-165% with BFRE and LLE at Post3 (P

  3. Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

    Science.gov (United States)

    Finch, Megan L; Passman, Adam M; Strauss, Robyn P; Yeoh, George C; Callus, Bernard A

    2015-01-01

    The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.

  4. Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations.

    Science.gov (United States)

    Leyva-Leyva, Margarita; López-Díaz, Annia; Barrera, Lourdes; Camacho-Morales, Alberto; Hernandez-Aguilar, Felipe; Carrillo-Casas, Erika M; Arriaga-Pizano, Lourdes; Calderón-Pérez, Jaime; García-Álvarez, Jorge; Orozco-Hoyuela, Gabriel; Piña-Barba, Cristina; Rojas-Martínez, Augusto; Romero-Díaz, Víktor; Lara-Arias, Jorge; Rivera-Bolaños, Nancy; López-Camarillo, César; Moncada-Saucedo, Nidia; Galván-De los Santos, Alejandra; Meza-Urzúa, Fátima; Villarreal-Gómez, Luis; Fuentes-Mera, Lizeth

    2015-11-01

    Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in

  5. Specific cerebral heat shock proteins and histamine receptor cross-talking mechanisms promote distinct lead-dependent neurotoxic responses in teleosts

    International Nuclear Information System (INIS)

    Giusi, Giuseppina; Alo, Raffaella; Crudo, Michele; Facciolo, Rosa Maria; Canonaco, Marcello

    2008-01-01

    Recent interests are beginning to be directed towards toxic neurobiological dysfunctions caused by lead (Pb) in aquatic vertebrates. In the present work, treatment with a maximum acceptable toxic concentration of this heavy metal was responsible for highly significant (p 2 R) antagonist cimetidine (Cim), as shown by the very robust (p 3 R) thioperamide (Thio), instead, blocked Pb-dependent up-regulatory trends of both chaperones in mostly hypothalamic areas. Moreover, intense neuronal damages of the above brain regions coincided with altered expressions of HSP70 and HSP90 when treated only with Cim. Overall these first results show that distinct H n R are able to exert a net neuroprotective role arising from their interaction with chaperones in fish exposed to Pb-dependent stressful conditions making this a potentially key interaction especially for T. pavo, aquatic species which plays an important ecological role towards the survival of other commercially vital fishes

  6. High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leading to decreased polypyrimidine tract binding protein-expression.

    Directory of Open Access Journals (Sweden)

    Rikard G Fred

    Full Text Available BACKGROUND: Prolonged periods of high glucose exposure results in human islet dysfunction in vitro. The underlying mechanisms behind this effect of high glucose are, however, unknown. The polypyrimidine tract binding protein (PTB is required for stabilization of insulin mRNA and the PTB mRNA 3'-UTR contains binding sites for the microRNA molecules miR-133a, miR-124a and miR-146. The aim of this study was therefore to investigate whether high glucose increased the levels of these three miRNAs in association with lower PTB levels and lower insulin biosynthesis rates. METHODOLOGY/PRINCIPAL FINDINGS: Human islets were cultured for 24 hours in the presence of low (5.6 mM or high glucose (20 mM. Islets were also exposed to sodium palmitate or the proinflammatory cytokines IL-1beta and IFN-gamma, since saturated free fatty acids and cytokines also cause islet dysfunction. RNA was then isolated for real-time RT-PCR analysis of miR-133a, miR-124a, miR-146, insulin mRNA and PTB mRNA contents. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. Synthetic miR-133a precursor and inhibitor were delivered to dispersed islet cells by lipofection, and PTB was analyzed by immunoblotting following culture at low or high glucose. Culture in high glucose resulted in increased islet contents of miR-133a and reduced contents of miR-146. Cytokines increased the contents of miR-146. The insulin and PTB mRNA contents were unaffected by high glucose. However, both PTB protein levels and insulin biosynthesis rates were decreased in response to high glucose. The miR-133a inhibitor prevented the high glucose-induced decrease in PTB and insulin biosynthesis, and the miR-133a precursor decreased PTB levels and insulin biosynthesis similarly to high glucose. CONCLUSION: Prolonged high-glucose exposure down-regulates PTB levels and insulin biosynthesis rates in human islets by increasing miR-133a levels. We propose that this mechanism

  7. Arranging eukaryotic nuclear DNA polymerases for replication: Specific interactions with accessory proteins arrange Pols α, δ, and ϵ in the replisome for leading-strand and lagging-strand DNA replication.

    Science.gov (United States)

    Kunkel, Thomas A; Burgers, Peter M J

    2017-08-01

    Biochemical and cryo-electron microscopy studies have just been published revealing interactions among proteins of the yeast replisome that are important for highly coordinated synthesis of the two DNA strands of the nuclear genome. These studies reveal key interactions important for arranging DNA polymerases α, δ, and ϵ for leading and lagging strand replication. The CMG (Mcm2-7, Cdc45, GINS) helicase is central to this interaction network. These are but the latest examples of elegant studies performed in the recent past that lead to a much better understanding of how the eukaryotic replication fork achieves efficient DNA replication that is accurate enough to prevent diseases yet allows evolution. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  8. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Roy Chen

    Full Text Available There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD. In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP and N-terminal prohormone brain natriuretic peptide (NT-proBNP in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80. These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.

  9. High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leading to decreased polypyrimidine tract binding protein-expression

    DEFF Research Database (Denmark)

    Fred, Rikard G; Bang-Berthelsen, Claus H; Mandrup-Poulsen, Thomas

    2010-01-01

    BACKGROUND: Prolonged periods of high glucose exposure results in human islet dysfunction in vitro. The underlying mechanisms behind this effect of high glucose are, however, unknown. The polypyrimidine tract binding protein (PTB) is required for stabilization of insulin mRNA and the PTB mRNA 3......'-UTR contains binding sites for the microRNA molecules miR-133a, miR-124a and miR-146. The aim of this study was therefore to investigate whether high glucose increased the levels of these three miRNAs in association with lower PTB levels and lower insulin biosynthesis rates. METHODOLOGY...... for real-time RT-PCR analysis of miR-133a, miR-124a, miR-146, insulin mRNA and PTB mRNA contents. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. Synthetic miR-133a precursor and inhibitor were delivered to dispersed islet cells by lipofection, and PTB...

  10. Selective targeting of the mTORC1/2 protein kinase complexes leads to antileukemic effects in vitro and in vivo

    International Nuclear Information System (INIS)

    Schuster, K; Zheng, J; Arbini, A A; Zhang, C C; Scaglioni, P P

    2011-01-01

    The BCR/ABL tyrosine kinase promotes leukemogenesis through activation of several targets that include the phosphoinositide 3-kinase (PI3K). Tyrosine kinase inhibitors (TKIs), which target BCR/ABL, induce striking clinical responses. However, therapy with TKIs is associated with limitations such as drug intolerance, inability to universally eradicate the disease and emergence of BCR/ABL drug-resistant mutants. To overcome these limitations, we tested whether inhibition of the PI3K/target of rapamycin (mTOR) signaling pathway has antileukemic effect in primary hematopoietic stem cells and BA/F3 cells expressing the BCR/ABL oncoprotein. We determined that dual inhibition of PI3K/mTOR causes growth arrest and apoptosis leading to profound antileukemic effects both in vitro and in vivo. We also established that pharmacologic inhibition of the mTORC1/mTORC2 complexes is sufficient to cause these antileukemic effects. Our results support the development of inhibitors of the mTORC1/2 complexes for the therapy of leukemias that either express BCR/ABL or display deregulation of the PI3K/mTOR signaling pathway

  11. Activation of the transcription factor carbohydrate-responsive element-binding protein by glucose leads to increased pancreatic beta cell differentiation in rats.

    Science.gov (United States)

    Soggia, A; Flosseau, K; Ravassard, P; Szinnai, G; Scharfmann, R; Guillemain, G

    2012-10-01

    Pancreatic cell development is a tightly controlled process. Although information is available regarding the mesodermal signals that control pancreatic development, little is known about the role of environmental factors such as nutrients, including glucose, on pancreatic development. We previously showed that glucose and its metabolism through the hexosamine biosynthesis pathway (HBP) promote pancreatic endocrine cell differentiation. Here, we analysed the role of the transcription factor carbohydrate-responsive element-binding protein (ChREBP) in this process. This transcription factor is activated by glucose, and has been recently described as a target of the HBP. We used an in vitro bioassay in which pancreatic endocrine and exocrine cells develop from rat embryonic pancreas in a way that mimics in vivo pancreatic development. Using this model, gain-of-function and loss-of-function experiments were undertaken. ChREBP was produced in the endocrine lineage during pancreatic development, its abundance increasing with differentiation. When rat embryonic pancreases were cultured in the presence of glucose or xylitol, the production of ChREBP targets was induced. Concomitantly, beta cell differentiation was enhanced. On the other hand, when embryonic pancreases were cultured with inhibitors decreasing ChREBP activity or an adenovirus producing a dominant-negative ChREBP, beta cell differentiation was reduced, indicating that ChREBP activity was necessary for proper beta cell differentiation. Interestingly, adenovirus producing a dominant-negative ChREBP also reduced the positive effect of N-acetylglucosamine, a substrate of the HBP acting on beta cell differentiation. Our work supports the idea that glucose, through the transcription factor ChREBP, controls beta cell differentiation from pancreatic progenitors.

  12. Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

    Science.gov (United States)

    Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

    2017-08-01

    Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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

  14. 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

  15. Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Wei-Ru Huang

    Full Text Available Avian reovirus (ARV protein p17 has been shown to regulate cell cycle and autophagy by activation of p53/PTEN pathway; nevertheless, it is still unclear how p53 and PTEN are activated by p17. Here, we report for the first time that p17 functions as a nucleoporin Tpr suppressor that leads to p53 nuclear accumulation and consequently activates p53, p21, and PTEN. The nuclear localization signal (119IAAKRGRQLD128 of p17 has been identified for Tpr binding. This study has shown that Tpr suppression occurs by p17 interacting with Tpr and by reducing the transcription level of Tpr, which together inhibit Tpr function. In addition to upregulation of PTEN by activation of p53 pathway, this study also suggests that ARV protein p17 acts as a positive regulator of PTEN. ARV p17 stabilizes PTEN by stimulating phosphorylation of cytoplasmic PTEN and by elevating Rak-PTEN association to prevent it from E3 ligase NEDD4-1 targeting. To activate PTEN, p17 is able to promote β-arrestin-mediated PTEN translocation from the cytoplasm to the plasma membrane via a Rock-1-dependent manner. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated downregulation of cyclin D1 and CDK4. Furthermore, Tpr and CDK4 knockdown increased virus production in contrast to depletion of p53, PTEN, and LC3 reducing virus yield. Taken together, our data suggest that p17-mediated Tpr suppression positively regulates p53, PTEN, and p21 and negatively regulates PI3K/AKT/mTOR and ERK signaling pathways, both of which are beneficial for virus replication.

  16. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  17. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  18. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Science.gov (United States)

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  19. Induction of heat shock proteins (hsp70) in the zebra mussel (Dreissena polymorpha) following exposure to platinum group metals (platinum, palladium and rhodium): Comparison with lead and cadmium exposures

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Christoph [Zoologisches Institut I-Oekologie, Universitaet Karlsruhe, Geb. 07.01, Kornblumenstrasse 13, D-76131 Karlsruhe (Germany); Zimmermann, Sonja [Zoologisches Institut I-Oekologie, Universitaet Karlsruhe, Geb. 07.01, Kornblumenstrasse 13, D-76131 Karlsruhe (Germany); Sures, Bernd [Zoologisches Institut I-Oekologie, Universitaet Karlsruhe, Geb. 07.01, Kornblumenstrasse 13, D-76131 Karlsruhe (Germany)]. E-mail: dc11@rz.uni-karlsruhe.de

    2005-10-05

    An increasing number of papers concentrate on the availability and uptake of platinum group elements (PGE) by different organisms. These metals are discharged into the environment from different anthropogenic sources, such as automobile catalytic converters, hospitals and other medical institutions. As the effects of these precious metals on organisms remain unclear, the induction of heat shock proteins (hsp70) in zebra mussels (Dreissena polymorpha) following exposure to soluble salts of platinum, palladium and rhodium was compared with the hsp70 induction in mussels following exposure to cadmium and lead. Mussels were sampled weekly during a period of 10 weeks and analyzed for their metal concentration and their hsp70 level. Highest metal uptake was found for Cd, followed by Pt, Pb and Pd. Rh demonstrated the lowest uptake rate. A clear time-dependent increase of hsp70 levels occurred in all exposed mussels. Concentrations of hsp70 started to rise between days 18 and 25, except for the Pt-exposed group, where the initial increase was between days 25 and 32. All groups reached maximal hsp70 concentrations at day 39. Subsequently, hsp70 levels decreased to initial levels for the remaining exposure period. Threshold metal levels for the hsp70 induction varied among the metals and increased in the order: Rh < Pd {<=} Pb < Pt < Cd. Highest hsp70 values were found for mussels exposed to Pd, with a 25-fold higher level than in the controls, followed by Pt- and Rh-exposed mussels, which showed a 19-fold increase. The hsp70 levels of the mussels exposed to Cd and Pb were much lower, showing 6- and 12-fold higher values than the control, respectively. The clear induction of hsp70 due to exposure to Pt, Pd and Rh gives evidence for strong cellular effects of these metals, especially, when compared with lead and cadmium. Among the metals tested, Pd seems to have the highest potential as inducer for hsp70 production due to its low threshold level in combination with the

  20. Induction of heat shock proteins (hsp70) in the zebra mussel (Dreissena polymorpha) following exposure to platinum group metals (platinum, palladium and rhodium): Comparison with lead and cadmium exposures

    International Nuclear Information System (INIS)

    Singer, Christoph; Zimmermann, Sonja; Sures, Bernd

    2005-01-01

    An increasing number of papers concentrate on the availability and uptake of platinum group elements (PGE) by different organisms. These metals are discharged into the environment from different anthropogenic sources, such as automobile catalytic converters, hospitals and other medical institutions. As the effects of these precious metals on organisms remain unclear, the induction of heat shock proteins (hsp70) in zebra mussels (Dreissena polymorpha) following exposure to soluble salts of platinum, palladium and rhodium was compared with the hsp70 induction in mussels following exposure to cadmium and lead. Mussels were sampled weekly during a period of 10 weeks and analyzed for their metal concentration and their hsp70 level. Highest metal uptake was found for Cd, followed by Pt, Pb and Pd. Rh demonstrated the lowest uptake rate. A clear time-dependent increase of hsp70 levels occurred in all exposed mussels. Concentrations of hsp70 started to rise between days 18 and 25, except for the Pt-exposed group, where the initial increase was between days 25 and 32. All groups reached maximal hsp70 concentrations at day 39. Subsequently, hsp70 levels decreased to initial levels for the remaining exposure period. Threshold metal levels for the hsp70 induction varied among the metals and increased in the order: Rh < Pd ≤ Pb < Pt < Cd. Highest hsp70 values were found for mussels exposed to Pd, with a 25-fold higher level than in the controls, followed by Pt- and Rh-exposed mussels, which showed a 19-fold increase. The hsp70 levels of the mussels exposed to Cd and Pb were much lower, showing 6- and 12-fold higher values than the control, respectively. The clear induction of hsp70 due to exposure to Pt, Pd and Rh gives evidence for strong cellular effects of these metals, especially, when compared with lead and cadmium. Among the metals tested, Pd seems to have the highest potential as inducer for hsp70 production due to its low threshold level in combination with the

  1. Tau protein

    DEFF Research Database (Denmark)

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc

    2011-01-01

    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14......-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. Methods: A total of 66 patients with MS and/or ON from...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased concentration of tau...

  2. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Regional Offices Labs and Research Centers Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... and protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  3. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  4. Lead - nutritional considerations

    Science.gov (United States)

    ... billion people had toxic (poisonous) blood lead levels. Food Sources Lead can be found in canned goods if there is lead solder in the ... to bottled water for drinking and cooking. Avoid canned goods from foreign ... cans goes into effect. If imported wine containers have a lead foil ...

  5. Newly formulated, protein quality-enhanced, extruded sorghum-, cowpea-, corn-, soya-, sugar- and oil-containing fortified-blended foods lead to adequate vitamin A and iron outcomes and improved growth compared with non-extruded CSB+ in rats.

    Science.gov (United States)

    Delimont, Nicole M; Fiorentino, Nicole M; Opoku-Acheampong, Alexander B; Joseph, Michael V; Guo, Qingbin; Alavi, Sajid; Lindshield, Brian L

    2017-01-01

    Corn and soyabean micronutrient-fortified-blended foods (FBF) are commonly used for food aid. Sorghum and cowpeas have been suggested as alternative commodities because they are drought tolerant, can be grown in many localities, and are not genetically modified. Change in formulation of blends may improve protein quality, vitamin A and Fe availability of FBF. The primary objective of this study was to compare protein efficiency, Fe and vitamin A availability of newly formulated extruded sorghum-, cowpea-, soya- and corn-based FBF, along with a current, non-extruded United States Agency for International Development (USAID) corn and soya blend FBF (CSB+). A second objective was to compare protein efficiency of whey protein concentrate (WPC) and soya protein isolate (SPI) containing FBF to determine whether WPC inclusion improved outcomes. Eight groups of growing rats ( n 10) consumed two white and one red sorghum-cowpea (WSC1 + WPC, WSC2 + WPC, RSC + WPC), white sorghum-soya (WSS + WPC) and corn-soya (CSB14 + WPC) extruded WPC-containing FBF, an extruded white sorghum-cowpea with SPI (WSC1 + SPI), non-extruded CSB+, and American Institute of Nutrition (AIN)-93G, a weanling rat diet, for 4 weeks. There were no significant differences in protein efficiency, Fe or vitamin A outcomes between WPC FBF groups. The CSB+ group consumed significantly less food, gained significantly less weight, and had significantly lower energy efficiency, protein efficiency and length, compared with all other groups. Compared with WSC1 + WPC, the WSC1 + SPI FBF group had significantly lower energy efficiency, protein efficiency and weight gain. These results suggest that a variety of commodities can be used in the formulation of FBF, and that newly formulated extruded FBF are of better nutritional quality than non-extruded CSB+.

  6. Screening a yeast promoter library leads to the isolation of the RP29/L32 and SNR17B/RPL37A divergent promoters and the discovery of a gene encoding ribosomal protein L37.

    Science.gov (United States)

    Santangelo, G M; Tornow, J; McLaughlin, C S; Moldave, K

    1991-08-30

    Two promoters (A7 and A23), isolated at random from the Saccharomyces cerevisiae genome by virtue of their capacity to activate transcription, are identical to known intergenic bidirectional promoters. Sequence analysis of the genomic DNA adjacent to the A7 promoter identified a split gene encoding ribosomal (r) protein L37, which is homologous to the tRNA-binding r-proteins, L35a (from human and rat) and L32 (from frogs).

  7. Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor β-activated kinase 1 (TAK1) recruitment.

    Science.gov (United States)

    Stack, Julianne; Hurst, Tara P; Flannery, Sinead M; Brennan, Kiva; Rupp, Sebastian; Oda, Shun-ichiro; Khan, Amir R; Bowie, Andrew G

    2013-11-22

    Vaccinia virus encodes a number of proteins that inhibit and manipulate innate immune signaling pathways that also have a role in virulence. These include A52, a protein shown to inhibit IL-1- and Toll-like receptor-stimulated NFκB activation, via interaction with interleukin-1 receptor-associated kinase 2 (IRAK2). Interestingly, A52 was also found to activate p38 MAPK and thus enhance Toll-like receptor-dependent IL-10 induction, which was TRAF6-dependent, but the manner in which A52 manipulates TRAF6 to stimulate p38 activation was unclear. Here, we show that A52 has a non-canonical TRAF6-binding motif that is essential for TRAF6 binding and p38 activation but dispensable for NFκB inhibition and IRAK2 interaction. Wild-type A52, but not a mutant defective in p38 activation and TRAF6 binding (F154A), caused TRAF6 oligomerization and subsequent TRAF6-TAK1 association. The crystal structure of A52 shows that it adopts a Bcl2-like fold and exists as a dimer in solution. Residue Met-65 was identified as being located in the A52 dimer interface, and consistent with that, A52-M65E was impaired in its ability to dimerize. A52-M65E although capable of interacting with TRAF6, was unable to cause either TRAF6 self-association, induce the TRAF6-TAK1 association, or activate p38 MAPK. The results suggest that an A52 dimer causes TRAF6 self-association, leading to TAK1 recruitment and p38 activation. This reveals a molecular mechanism whereby poxviruses manipulate TRAF6 to activate MAPKs (which can be proviral) without stimulating antiviral NFκB activation.

  8. 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

  9. 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

  10. 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.

  11. Uranium-lead systematics

    International Nuclear Information System (INIS)

    Wickman, F.E.

    1983-01-01

    The method of Levchenkov and Shukolyukov for calculating age and time disturbance of minerals without correction for original lead is generalized to include the cases when (1) original lead and radiogenic lead leach differently, and (2) the crystals studied consist of a core and a mantle. It is also shown that a straight line obtained from the solution of the equations is the locus of the isotopic composition of original lead. (Auth.)

  12. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  13. Lead Poisoning (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Lead Poisoning KidsHealth / For Parents / Lead Poisoning What's in ... Print en español La intoxicación por plomo About Lead Poisoning If you have young kids, it's important ...

  14. Superconductivity in nanostructured lead

    Science.gov (United States)

    Lungu, Anca; Bleiweiss, Michael; Amirzadeh, Jafar; Saygi, Salih; Dimofte, Andreea; Yin, Ming; Iqbal, Zafar; Datta, Timir

    2001-01-01

    Three-dimensional nanoscale structures of lead were fabricated by electrodeposition of pure lead into artificial porous opal. The size of the metallic regions was comparable to the superconducting coherence length of bulk lead. Tc as high as 7.36 K was observed, also d Tc/d H was 2.7 times smaller than in bulk lead. Many of the characteristics of these differ from bulk lead, a type I superconductor. Irreversibility line and magnetic relaxation rates ( S) were also studied. S( T) displayed two maxima, with a peak value about 10 times smaller than that of typical high- Tc superconductors.

  15. 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

  16. ALICE: Simulated lead-lead collision

    CERN Multimedia

    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.

  17. Secondary lead production

    Energy Technology Data Exchange (ETDEWEB)

    Hollis, R.G.

    1990-10-16

    This invention is concerned with the efficient recovery of soft lead from the paste component of used automobile lead-acid storage batteries. According to the invention, a scrap which contains lead oxide, lead sulfate, and antimony in an oxidized state is processed in the following steps to recover lead. A refractory lined reaction vessel is continuously charged with the scrap, along with a reductant effective for reducing lead oxide. The charged material is melted and agitated by means of a submerged lance at 900-1150{degree}C whereby some of the lead oxide of the scrap is reduced to form molten lead. A slag layer is then formed above the molten lead, and an amount of lead oxide is maintained in the slag layer. The molten lead, now containing under 0.5 wt % of antimony, is removed, and the antimony oxide in the scrap is concentrated as oxide in the slag layer. Preferred embodiments of the invention result in the production, in a single step, of a soft lead substantially free of antimony. The slag may be subsequently treated to reduce the antimony oxide and produce a valuable antimony-lead product. Further advantages of the process are that a wet battery paste may be used as the feed without prior drying, and the process can be conducted at a temperature 100-150{degree}C lower than in previously known methods. In addition, a smaller reactor can be employed which reduces both capital cost and fuel costs. The process of the invention is illustrated by descriptions of pilot plant tests. 1 fig.

  18. 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.

  19. 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.

  20. Mutation of Rice BC12/GDD1, Which Encodes a Kinesin-Like Protein That Binds to a GA Biosynthesis Gene Promoter, Leads to Dwarfism with Impaired Cell Elongation[W][OA

    Science.gov (United States)

    Li, Juan; Jiang, Jiafu; Qian, Qian; Xu, Yunyuan; Zhang, Cui; Xiao, Jun; Du, Cheng; Luo, Wei; Zou, Guoxing; Chen, Mingluan; Huang, Yunqing; Feng, Yuqi; Cheng, Zhukuan; Yuan, Ming; Chong, Kang

    2011-01-01

    The kinesins are a family of microtubule-based motor proteins that move directionally along microtubules and are involved in many crucial cellular processes, including cell elongation in plants. Less is known about kinesins directly regulating gene transcription to affect cellular physiological processes. Here, we describe a rice (Oryza sativa) mutant, gibberellin-deficient dwarf1 (gdd1), that has a phenotype of greatly reduced length of root, stems, spikes, and seeds. This reduced length is due to decreased cell elongation and can be rescued by exogenous gibberellic acid (GA3) treatment. GDD1 was cloned by a map-based approach, was expressed constitutively, and was found to encode the kinesin-like protein BRITTLE CULM12 (BC12). Microtubule cosedimentation assays revealed that BC12/GDD1 bound to microtubules in an ATP-dependent manner. Whole-genome microarray analysis revealed the expression of ent-kaurene oxidase (KO2), which encodes an enzyme involved in GA biosynthesis, was downregulated in gdd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that GDD1 bound to the element ACCAACTTGAA in the KO2 promoter. In addition, GDD1 was shown to have transactivation activity. The level of endogenous GAs was reduced in gdd1, and the reorganization of cortical microtubules was altered. Therefore, BC12/GDD1, a kinesin-like protein with transcription regulation activity, mediates cell elongation by regulating the GA biosynthesis pathway in rice. PMID:21325138

  1. Lead poisoning in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Bond, E; Kubin, R

    1949-01-01

    Diagnosis was made from clinical observation and laboratory examination of nine cases. A successful treatment is described based on the similarity of the metabolism of lead and calcium, the lead being deposited in the bones where it is harmless, if it remains there. Details are given of the treatment.

  2. 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

  3. Leading Educational Change Wisely

    Science.gov (United States)

    Forrester, Gillian

    2011-01-01

    In this article, the author reviews Christopher Branson's book entitled "Leading Educational Change Wisely". The book provides an alternative and engaging perspective on leading educational change. Branson utilises "wisdom" as its central conceptual device to present a thought-provoking and philosophical account on how leaders are able to build a…

  4. Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women.

    Science.gov (United States)

    Faber, Joyce; Berkhout, Marloes; Vos, Arjan P; Sijben, John W C; Calder, Philip C; Garssen, Johan; van Helvoort, Ardy

    2011-05-01

    Immune modulatory effects of EPA and DHA are well described. However, these fatty acids must be effectively incorporated into cell membrane phospholipids to modify cell function. To address the absence of human data regarding short-term incorporation, the present study investigated the incorporation of EPA and DHA into white blood cells (WBC) at different time points during 1 wk of supplementation with a medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides. Additionally, the effects on ex vivo immune function were determined. In a single-arm, open label study, 12 healthy men and women consumed 2 × 200 mL of medical food providing 2.4 g EPA, 1.2 g DHA, 39.7 g protein (including 4.4 g L-leucine), and 5.6 g oligosaccharides daily. Blood samples were taken at d 0 (baseline), 1, 2, 4, and 7. Within 1 d of nutritional intervention, the percentage of EPA in phospholipids of WBC increased from 0.5% at baseline to 1.3% (P blood cultures was significantly increased within 1 wk. Nutritional supplementation with a fish oil-enriched medical food significantly increased the percentage of EPA in phospholipids of WBC within 1 wk. Simultaneously, ex vivo immune responsiveness to LPS increased significantly. These results hold promise for novel applications such as fast-acting nutritional interventions in cancer patients, which should be investigated in future studies.

  5. Lead-free piezoceramics.

    Science.gov (United States)

    Saito, Yasuyoshi; Takao, Hisaaki; Tani, Toshihiko; Nonoyama, Tatsuhiko; Takatori, Kazumasa; Homma, Takahiko; Nagaya, Toshiatsu; Nakamura, Masaya

    2004-11-04

    Lead has recently been expelled from many commercial applications and materials (for example, from solder, glass and pottery glaze) owing to concerns regarding its toxicity. Lead zirconium titanate (PZT) ceramics are high-performance piezoelectric materials, which are widely used in sensors, actuators and other electronic devices; they contain more than 60 weight per cent lead. Although there has been a concerted effort to develop lead-free piezoelectric ceramics, no effective alternative to PZT has yet been found. Here we report a lead-free piezoelectric ceramic with an electric-field-induced strain comparable to typical actuator-grade PZT. We achieved this through the combination of the discovery of a morphotropic phase boundary in an alkaline niobate-based perovskite solid solution, and the development of a processing route leading to highly textured polycrystals. The ceramic exhibits a piezoelectric constant d33 (the induced charge per unit force applied in the same direction) of above 300 picocoulombs per newton (pC N(-1)), and texturing the material leads to a peak d33 of 416 pC N(-1). The textured material also exhibits temperature-independent field-induced strain characteristics.

  6. Lead poisoning in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, M R; Lewis, G

    1963-08-03

    Within a short period, 14 cases of lead poisoning in the dogs have been encountered. A detailed record appears justified as no published reference can be found to this condition occurring in Britain and because reports from other countries stress the similarity of the clinical manifestations of lead poisoning to those of the common infections of the dog. Five of the 14 clinical cases of lead poisoning are described. The available literature is reviewed and the diagnosis and significance of the condition discussed. 19 references, 2 tables.

  7. 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...

  8. Radiation shielding lead shield

    International Nuclear Information System (INIS)

    Dei, Shoichi.

    1991-01-01

    The present invention concerns lead shields for radiation shielding. Shield boxes are disposed so as to surround a pipeline through which radioactive liquids, mists or like other objects are passed. Flanges are formed to each of the end edges of the shield boxes and the shield boxes are connected to each other by the flanges. Upon installation, empty shield boxes not charged with lead particles and iron plate shields are secured at first at the periphery of the pipeline. Then, lead particles are charged into the shield boxes. This attains a state as if lead plate corresponding to the depth of the box is disposed. Accordingly, operations for installation, dismantling and restoration can be conducted in an empty state with reduced weight to facilitate the operations. (I.S.)

  9. Lead poisoning in mink

    Energy Technology Data Exchange (ETDEWEB)

    Purdy, J G

    1962-03-01

    This paper describes a case of lead poisoning in minks. The mink were housed in pens which had been painted with a bridge paint containing lead. They had chewed on the pen and ingested the paint. The animals that did not die were moved to new pens, and vitamin D and calcium gluconate were added to their diets. In three days, a marked improvement was seen in the food and water consumption, and convolutions became less frequent.

  10. 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.

  11. 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

  12. Overexpression of a Medicago truncatula stress-associated protein gene (MtSAP1) leads to nitric oxide accumulation and confers osmotic and salt stress tolerance in transgenic tobacco.

    Science.gov (United States)

    Charrier, Aurélie; Planchet, Elisabeth; Cerveau, Delphine; Gimeno-Gilles, Christine; Verdu, Isabelle; Limami, Anis M; Lelièvre, Eric

    2012-08-01

    The impact of Medicago truncatula stress-associated protein gene (MtSAP1) overexpression has been investigated in Nicotiana tabacum transgenic seedlings. Under optimal conditions, transgenic lines overexpressing MtSAP1 revealed better plant development and higher chlorophyll content as compared to wild type seedlings. Interestingly, transgenic lines showed a stronger accumulation of nitric oxide (NO), a signaling molecule involved in growth and development processes. This NO production seemed to be partially nitrate reductase dependent. Due to the fact that NO has been also reported to play a role in tolerance acquisition of plants to abiotic stresses, the responses of MtSAP1 overexpressors to osmotic and salt stress have been studied. Compared to the wild type, transgenic lines were less affected in their growth and development. Moreover, NO content in MtSAP1 overexpressors was always higher than that detected in wild seedlings under stress conditions. It seems that this better tolerance induced by MtSAP1 overexpression could be associated with this higher NO production that would enable seedlings to reach a high protection level to prepare them to cope with abiotic stresses.

  13. Protein surface shielding agents in protein crystallization

    International Nuclear Information System (INIS)

    Hašek, J.

    2011-01-01

    The crystallization process can be controlled by protein surface shielding agents blocking undesirable competitive adhesion modes during non-equilibrium processes of deposition of protein molecules on the surface of growing crystalline blocks. The hypothesis is based on a number of experimental proofs from diffraction experiments and also retrieved from the Protein Data Bank. The molecules adhering temporarily on the surface of protein molecules change the propensity of protein molecules to deposit on the crystal surface in a definite position and orientation. The concepts of competitive adhesion modes and protein surface shielding agents acting on the surface of molecules in a non-equilibrium process of protein crystallization provide a useful platform for the control of crystallization. The desirable goal, i.e. a transient preference of a single dominating adhesion mode between protein molecules during crystallization, leads to uniform deposition of proteins in a crystal. This condition is the most important factor for diffraction quality and thus also for the accuracy of protein structure determination. The presented hypothesis is a generalization of the experimentally well proven behaviour of hydrophilic polymers on the surface of protein molecules of other compounds

  14. 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.

  15. Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system.

    Science.gov (United States)

    Sane, Ramola; Agarwal, Sagar; Mittapalli, Rajendar K; Elmquist, William F

    2013-04-01

    The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar. Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics. Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB. We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice. Initially, the mice were administered 2.5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined. The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0.82, as compared with 3.5 in Mdr1a/b(-/-) mice, 6.6 in Bcrp1(-/-) mice, and 15 in Mdr1a/b(-/-)Bcrp1(-/-) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar. The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined. The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes. However, the ED50 was lower for Mdr1a/b(-/-) mice compared with Bcrp1(-/-) mice. These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose. Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma.

  16. The effects of arbuscular mycorrhizal fungi on glomalin-related soil protein distribution, aggregate stability and their relationships with soil properties at different soil depths in lead-zinc contaminated area.

    Directory of Open Access Journals (Sweden)

    Yurong Yang

    Full Text Available Glomalin-related soil protein (GRSP, a widespread glycoprotein produced by arbuscular mycorrhizal fungi (AMF, is crucial for ecosystem functioning and ecological restoration. In the present study, an investigation was conducted to comprehensively analyze the effects of heavy metal (HM contamination on AMF status, soil properties, aggregate distribution and stability, and their correlations at different soil depths (0-10, 10-20, 20-30, 30-40 cm. Our results showed that the mycorrhizal colonization (MC, hyphal length density (HLD, GRSP, soil organic matter (SOM and soil organic carbon (SOC were significantly inhibited by Pb compared to Zn at 0-20 cm soil depth, indicating that HM had significant inhibitory effects on AMF growth and soil properties, and that Pb exhibited greater toxicity than Zn at shallow layer of soil. Both the proportion of soil large macroaggregates (>2000 μm and mean weight diameter (MWD were positively correlated with GRSP, SOM and SOC at 0-20 cm soil depth (P < 0.05, proving the important contributions of GRSP, SOM and SOC for binding soil particles together into large macroaggregates and improving aggregate stability. Furthermore, MC and HLD had significantly positive correlation with GRSP, SOM and SOC, suggesting that AMF played an essential role in GRSP, SOM and SOC accumulation and subsequently influencing aggregate formation and particle-size distribution in HM polluted soils. Our study highlighted that the introduction of indigenous plant associated with AMF might be a successful biotechnological tool to assist the recovery of HM polluted soils, and that proper management practices should be developed to guarantee maximum benefits from plant-AMF symbiosis during ecological restoration.

  17. The effects of arbuscular mycorrhizal fungi on glomalin-related soil protein distribution, aggregate stability and their relationships with soil properties at different soil depths in lead-zinc contaminated area.

    Science.gov (United States)

    Yang, Yurong; He, Chuangjun; Huang, Li; Ban, Yihui; Tang, Ming

    2017-01-01

    Glomalin-related soil protein (GRSP), a widespread glycoprotein produced by arbuscular mycorrhizal fungi (AMF), is crucial for ecosystem functioning and ecological restoration. In the present study, an investigation was conducted to comprehensively analyze the effects of heavy metal (HM) contamination on AMF status, soil properties, aggregate distribution and stability, and their correlations at different soil depths (0-10, 10-20, 20-30, 30-40 cm). Our results showed that the mycorrhizal colonization (MC), hyphal length density (HLD), GRSP, soil organic matter (SOM) and soil organic carbon (SOC) were significantly inhibited by Pb compared to Zn at 0-20 cm soil depth, indicating that HM had significant inhibitory effects on AMF growth and soil properties, and that Pb exhibited greater toxicity than Zn at shallow layer of soil. Both the proportion of soil large macroaggregates (>2000 μm) and mean weight diameter (MWD) were positively correlated with GRSP, SOM and SOC at 0-20 cm soil depth (P soil particles together into large macroaggregates and improving aggregate stability. Furthermore, MC and HLD had significantly positive correlation with GRSP, SOM and SOC, suggesting that AMF played an essential role in GRSP, SOM and SOC accumulation and subsequently influencing aggregate formation and particle-size distribution in HM polluted soils. Our study highlighted that the introduction of indigenous plant associated with AMF might be a successful biotechnological tool to assist the recovery of HM polluted soils, and that proper management practices should be developed to guarantee maximum benefits from plant-AMF symbiosis during ecological restoration.

  18. 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...

  19. Learn about Lead

    Science.gov (United States)

    ... Search Main menu Environmental Topics Air Bed Bugs Chemicals and Toxics Environmental Information by Location Greener Living Health Land, ... it has some beneficial uses, it can be toxic to humans and animals causing of health ... some types of industrial facilities, and past use of lead-based paint ...

  20. Leading Causes of Blindness

    Science.gov (United States)

    ... have cataracts. They are the leading cause of blindness in the world. By age 80, more than half of all people in the United States either will have a cataract or have had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to ...

  1. Lead User Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Larsen, Henry

    2015-01-01

    covers the opposite view, where a company actively searches and involves lead users, however, with limited success also. Based on both cases, we analyze how, in these emerging processes of relating, meaning is co-created in a way that narrows the shared conceptual space for imagination and collaboration...

  2. 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…

  3. Leading through Conflict

    Science.gov (United States)

    Gerzon, Mark

    2006-01-01

    This article talks about leading significant learning opportunities through conflict of ideas in a school system. Catalyzing school change can turn emotional differences of opinion into learning opportunities. Leaders who want to deal effectively with these challenging, often tense situations need to be more than good managers. They need to be…

  4. Lead Time Study,

    Science.gov (United States)

    1982-05-01

    1979, the number of titanium fabrications dropped from 16 to 4, primarily because of the sponge shortage and EPA and OSHA requirements. Non-military...East - Taiwan, Korea, Singapore, Malaysia and Hong Kong. In addition, a significant amount of ceramic parts, lead frames and high technology

  5. Lead pollution in Islamabad

    International Nuclear Information System (INIS)

    Mohammad, D.; Khatoon, N.; Ishaque, M.; Ahmed, I.

    1997-01-01

    Lead pollution of urban area emanating from the vehicular exhaust alone is being labeled as one of the worst form of environmental degradation attracting our attention for remediation. For factual assessment samples were collected from different areas of Islamabad. These samples consisted of tree scrapings / peelings, which were dried and ground before undertaking analysis for the lead content. The samples were digested with an acid mixture to remove the organic matter and analyzed using GFAAS technique. A total of 81 samples have been analyzed. The results sowed a lead content varying in the range of 8-474 Mu g g/sup -1/) and 23 samples with Pb content <50 Mu g g-1 (8.0-50.0 Mu g g/sup -1/). Most of the samples also contained some growth which consisted of bacterial, algae and fugal cells and the results have been explained on the basis of Pb absorption by these cells. The procedure followed in this study is recommended for evaluation of lead pollution in urban areas. (author)

  6. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    increase in the production of poultry meat at a reasonable cost (Alam et al., ...... 36(4): 537-541. Taggart MA, Figuerola J, Green AJ, Mateo R, Deacon C, Osborn D, ... selenium, lead and copper levels in the livers and bones of five waterfowl ...

  7. Intoxication for lead

    International Nuclear Information System (INIS)

    Velez, Ruben Dario; Tamayo, Margarita Maria

    1999-01-01

    We present a case of a hospitalized girl with bronchopneumonia, who needed mechanic ventilation. Also she had a developmental delay and Burtons border in gums. Radiological studies showed dense transverse metaphiseal bands in long bones and hyperdensity in basal ganglia. We found high serum lead levels

  8. Lead Thickness Measurements

    International Nuclear Information System (INIS)

    Rucinski, R.

    1998-01-01

    The preshower lead thickness applied to the outside of D-Zero's superconducting solenoid vacuum shell was measured at the time of application. This engineering documents those thickness measurements. The lead was ordered in sheets 0.09375-inch and 0.0625-inch thick. The tolerance on thickness was specified to be +/- 0.003-inch. The sheets all were within that thickness tolerance. The nomenclature for each sheet was designated 1T, 1B, 2T, 2B where the numeral designates it's location in the wrap and 'T' or 'B' is short for 'top' or 'bottom' half of the solenoid. Micrometer measurements were taken at six locations around the perimeter of each sheet. The width,length, and weight of each piece was then measured. Using an assumed pure lead density of 0.40974 lb/in 3 , an average sheet thickness was calculated and compared to the perimeter thickness measurements. In every case, the calculated average thickness was a few mils thinner than the perimeter measurements. The ratio was constant, 0.98. This discrepancy is likely due to the assumed pure lead density. It is not felt that the perimeter is thicker than the center regions. The data suggests that the physical thickness of the sheets is uniform to +/- 0.0015-inch.

  9. Anatomy of lead poisoning

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Results: The primary form of lead toxicity is by oxidative stress mechanisms, apoptosis and necrosis involving ... néfastes sur la reproduction à l'avenir. Résultats:La forme ... prostate cancers, abnormal sexual ..... ensure this work is a success.

  10. 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

  11. Total contribution of airborne lead to blood lead.

    OpenAIRE

    Manton, W I

    1985-01-01

    A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone.

  12. Total contribution of airborne lead to blood lead.

    Science.gov (United States)

    Manton, W I

    1985-01-01

    A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone. PMID:3970881

  13. Deficiency of RgpG Causes Major Defects in Cell Division and Biofilm Formation, and Deficiency of LytR-CpsA-Psr Family Proteins Leads to Accumulation of Cell Wall Antigens in Culture Medium by Streptococcus mutans.

    Science.gov (United States)

    De, Arpan; Liao, Sumei; Bitoun, Jacob P; Roth, Randy; Beatty, Wandy L; Wu, Hui; Wen, Zezhang T

    2017-09-01

    Streptococcus mutans is known to possess rhamnose-glucose polysaccharide (RGP), a major cell wall antigen. S. mutans strains deficient in rgpG , encoding the first enzyme of the RGP biosynthesis pathway, were constructed by allelic exchange. The rgpG deficiency had no effect on growth rate but caused major defects in cell division and altered cell morphology. Unlike the coccoid wild type, the rgpG mutant existed primarily in chains of swollen, "squarish" dividing cells. Deficiency of rgpG also causes significant reduction in biofilm formation ( P cell envelope biogenesis, were constructed using the rgpG mutant. There were no major differences in growth rates between the wild-type strain and the rgpG brpA and rgpG psr double mutants, but the growth rate of the rgpG brpA psr triple mutant was reduced drastically ( P cells with multiple asymmetric septa. When analyzed by immunoblotting, the rgpG mutant displayed major reductions in cell wall antigens compared to the wild type, while little or no signal was detected with the double and triple mutants and the brpA and psr single mutants. These results suggest that RgpG in S. mutans plays a critical role in cell division and biofilm formation and that BrpA and Psr may be responsible for attachment of cell wall antigens to the cell envelope. IMPORTANCE Streptococcus mutans , a major etiological agent of human dental caries, produces rhamnose-glucose polysaccharide (RGP) as the major cell wall antigen. This study provides direct evidence that deficiency of RgpG, the first enzyme of the RGP biosynthesis pathway, caused major defects in cell division and morphology and reduced biofilm formation by S. mutans , indicative of a significant role of RGP in cell division and biofilm formation in S. mutans These results are novel not only in S. mutans , but also other streptococci that produce RGP. This study also shows that the LytR-CpsA-Psr family proteins BrpA and Psr in S. mutans are involved in attachment of RGP and probably

  14. Safety and Health Topics: Lead

    Science.gov (United States)

    ... ammunition, pipes, cable covering, building material, solder, radiation shielding, collapsible tubes, and fishing weights. Lead is also ... lead linings in tanks and radiation protection, leaded glass, work involving soldering, and other work involving lead ...

  15. Skin toxicology of lead species evaluated by their permeability and proteomic profiles: a comparison of organic and inorganic lead.

    Science.gov (United States)

    Pan, Tai-Long; Wang, Pei-Wen; Al-Suwayeh, Saleh A; Chen, Chih-Chieh; Fang, Jia-You

    2010-08-01

    Lead compounds are known to cause cytotoxicity and genotoxicity. Lead absorption by the skin is an important route through which this metal enters the body. The purpose of this work was to evaluate the skin permeability and toxicological profiles of two lead species, lead acetate and lead nitrate. This study assessed lead-induced toxicity mechanisms by focusing on the histopathology, proteomics, cell growth, and cellular ATP. In vitro skin permeation assays showed that there was no significant difference of lead accumulation within and across the skin between the two lead species. The presence of simulated sweat reduced the skin uptake of lead. The skin deposition of lead acetate was greater than that of lead nitrate with in vivo topical application. On the other hand, lead nitrate produced greater changes in the skin's histology and proteomic profiles compared to lead acetate. Four protein spots which showed significant changes were identified and are discussed in this study. These included glucose-related protein precursor (GRP) 78, K14, alpha-actin, and Rho GDP-dissociation inhibitor 2 (RhoGDI2). These proteins are respectively associated with oxidative stress, apoptosis, wound healing, and proliferation. Lead presented a biphasic pattern on cell growth and intracellular ATP content, with a stimulating effect at low concentrations and an inhibitory effect on cell proliferation at higher concentrations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Polymer Directed Protein Assemblies

    Directory of Open Access Journals (Sweden)

    Patrick van Rijn

    2013-05-01

    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  17. Lead poisoning: The invisible disease

    Science.gov (United States)

    Friend, Milton

    1989-01-01

    Lead poisoning is an intoxication resulting from absorption of hazardous levels of lead into body tissues. Lead pellets from shot shells, when ingested, are the most common source of lead poisoning in migratory birds. Other far less common sources include lead fishing sinkers, mine wastes, paint pigments, bullets, and other lead objects that are swallowed.

  18. Lead toxicity: current concerns.

    OpenAIRE

    Goyer, R A

    1993-01-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has be...

  19. 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.

  20. Leading change: 3--implementation.

    Science.gov (United States)

    Kerridge, Joanna

    The potential for all staff to contribute to service improvement, irrespective of discipline, role or function, is outlined in the 2011 NHS leadership framework. This advocates developing the skills of the entire workforce to create a climate of continuous service improvement. As nurses are often required to take the lead in managing change in clinical practice, this final article in a three-part series focuses on implementing ande potentia reviewing change.

  1. 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)

  2. 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.

  3. 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.

  4. Leading Change, Adding Value.

    Science.gov (United States)

    Evans, Nick

    2016-09-12

    Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It is designed to build on Compassion in Practice (CiP), which was published 3 years ago and set out the 6Cs: compassion, care, commitment, courage, competence and communication. CiP established the values at the heart of nursing and midwifery, while the new framework sets out how staff can help transform the health and care sectors to meet the aims of the NHS England's Five Year Forward View.

  5. 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...... is not to accumulate state or market wealth, but for entrepreneurial skills to become tools towards the liberation of the individual from oppressive systems of control – essentially to add public value rather than economic value. In this presentation I will sketch an anarchist perspective on entrepreneurship, looking...

  6. Remediation of lead contaminated soil

    International Nuclear Information System (INIS)

    Urban, W.; Krishnamurthy, S.

    1992-01-01

    Lead contaminated soil in urban area is of major concern because of the potential health risk to children. Many studies have established a direct correlation between lead in soil and elevated blood lead levels in children. In Minneapolis, Minnesota, Mielke et al. (1983) reported that 50% of the Hmong children with lead poisioning were in areas where soil lead levels were between 500 and 1000 micrograms per gram (ug/g), and 40% of the children suffering from lead poisioning lived in areas where soil lead levels exceeded 1000 ug/g. In urban areas, lead pollution in soil has come from many different sources. The sources include lead paint, lead batteries and automobile exhaust. Olson and Skogerbee (1975) found the following lead compounds in soils where the primary source of pollution was from automobiles: lead sulfate, lead oxide, lead dioxide, lead sulfide, and metallic lead. The primary form of lead found was lead sulfate. Lead sulfate, lead tetraoxide, white lead, and other forms of lead have been used in the manufacture of paints for houses. At present, two remediation techniques, solidification and Bureau of Mines fluosilicic acid leaching, are available for lead-contaminated sites. The objective of the present investigation at the Risk Reduction Engineering Laboratory (RREL), Edison, was to try to solubilize the lead species by appropriate reagents and then recover the contaminants by precipitation as lead sulfate, using environmentally acceptable methods. The apparatus used for mixing was a LabMaster mixer, with variable speed and high-shear impeller. Previous work had used nitric acid for dissolving metallic lead. Owing to the environmental concerns, it was decided to use acetic acid in the presence of oxygen. The theoretical justification for this approach is the favorable redox potential for the reaction between metallic lead, acetic acid, and gaseous oxygen

  7. The optimum lead thickness for lead-activation detectors

    International Nuclear Information System (INIS)

    Si Fenni; Hu Qingyuan

    2009-01-01

    The optimum lead thickness for lead-activation detectors has been studied in this paper. First existence of the optimum lead thickness is explained theoretically. Then the optimum lead thickness is obtained by two methods, MCNP5 calculation and mathematical estimation. At last factors which affect the optimum lead thickness are discussed. It turns out that the optimum lead thickness is irrelevant to incident neutron energies. It is recommended 2.5 cm generally.

  8. Who will lead?

    Science.gov (United States)

    Gustafson, R P; Schlosser, J R

    1997-01-01

    A recent survey conducted by the UCLA Center for Health Services Management and the Physician Executive Practice of Heidrick & Struggles, an executive search firm, sheds light on the emerging physician executive's role. The goal of the research was to identify success factors as a means of evaluating and developing effective industry leaders. Respondents were asked to look at specific skills in relation to nine categories: Communication, leadership, interpersonal skills, self-motivation/management, organizational knowledge, organizational strategy, administrative skills, and thinking. Communication, leadership, and self-motivation/management emerged, in that order, as the three most important success factors for physician executives. An individual's general competencies, work styles, and ability to lead others through organizational restructuring defines his or her appropriateness for managerial positions in the health care industry.

  9. Lead and lead-based alloys as waste matrix materials

    International Nuclear Information System (INIS)

    Arustamov, A.E.; Ojovan, M.I.; Kachalov, M.B.

    1999-01-01

    Metals and alloys with relatively low melting temperatures such as lead and lead-based alloys are considered in Russia as prospective matrices for encapsulation of spent nuclear fuel in containers in preparation for final disposal in underground repositories. Now lead and lead-based alloys are being used for conditioning spent sealed radioactive sources at radioactive waste disposal facilities

  10. Lead poisoning in calves

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, J E

    1964-01-01

    Over a three-year period a farmer lost seven calves in their second month of age. One year ago a tentative diagnosis of rabies was given and a brain was submitted to the Health of Animals Division for examination. No Negri bodies were found. The owner stated that the calves first appeared listless and later exhibited severe nervous signs. Deaths occurred in from one to 24 hours after onset of signs. Appetite and bowel movements were normal. There was no increase in temperature. The calf would lie quietly for an interval, then rise, run down the alley, press against a wall, and go into a convulsion. It acted as if it were in severe pain and during one of the intermittent convulsions, it jumped over a three-foot partition. This calf was sent to the Regional Veterinary Laboratory at Brighton for necropsy. The calf had been dead for 72 hours when submitted to the laboratory. The only gross findings were of mild pleurisy and hemorrhage on the kidney. A tentative diagnosis of lead poisoning was offered and specimens sent to the Division of Pharmacology and Toxicology, Ontario Veterinary College.

  11. 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

  12. 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. *

  13. Manurial properties of lead nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Berry, R A

    1924-01-01

    Water culture, pot and field experiments were conducted in order to determine the toxic and stimulating limit of lead nitrate in solution. Oats and rye grass were evaluated for evidence of lead poisoning. Results indicate that except in solutions of fairly high concentration, soil adsorbs the lead and destroys the toxicity of soluble lead salts. There was evidence to show that the addition of lead salts increased the rate of nitrification in soil.

  14. 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

  15. 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

  16. 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 ...

  17. 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 ...

  18. 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)

  19. Experimental lead poisoning in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Silven, L.

    1967-01-01

    Poisoning of water fowl due to the intake of lead shot is not rare in the USA. In order to study this kind of poisoning more closely domestic fowl were given varying amounts of lead shot and lead powder. This treatment did not provoke any symptoms of poisoning. Chemical analyses of different organs, muscles, skeleton and eggs yielded low lead values. It is concluded that the low toxicity of lead administered as lead shot to the domestic fowl is due to a low absorption rate from the gastro-intestinal tract.

  20. Decontamination and coating of lead

    International Nuclear Information System (INIS)

    Rankin, W.N.; Bush, S.P.; Lyon, C.E.; Walker, V.

    1988-01-01

    Technology is being developed to decontaminate lead used in shielding applications in contaminated environments for recycle as shieldings. Technology is also being developed to coat either decontaminated lead or new lead before it is used in contaminated environments. The surface of the coating is expected to be much easier to decontaminate than the original lead surface. If contamination becomes severely embedded in the coating and cannot be removed, it can be easily cut with a knife and removed from the lead. The used coating can be disposed of as radioactive (hot hazardous) waste. The lead can then be recoated for further use as a shielding material

  1. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    International Nuclear Information System (INIS)

    Yu, P.

    2007-01-01

    The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  2. Forming lead-based anodes

    Energy Technology Data Exchange (ETDEWEB)

    Ogorodnichuk, V I; Voitsekhovich, R I

    1972-01-01

    Lead-based anodes can be produced by forming a layer of lead dioxide by chemical treatment in a solution of sulfuric acid in potassium permanganate at 80 to 100/sup 0/. The solution is mixed by compressed air. (RWR)

  3. Correlation between some parameters of lead absorption and lead intoxication

    Science.gov (United States)

    Waldron, H. A.

    1971-01-01

    Waldron, H. A. (1971).Brit. J. industr. Med.,28, 195-199. Correlation between some parameters of lead absorption and lead intoxication. Use has been made of data collected over a number of years from workers exposed to a lead hazard in a motor-car factory. The correlations between various parameters of lead absorption and lead intoxication were computed, including blood and urine lead concentrations, urinary coproporphyrin, ALA and PBG concentrations, and haemoglobin concentration. In all, 15 correlation coefficients were calculated, of which only six showed a statistically significant result (i.e., Plead and urine lead (r = 0·38, Plead and coproporphyrin (r = 0·42, Plead and ALA (r = 0·43, Plead and PBG (r = 0·19, P<0·05). PMID:5572689

  4. Common ECG Lead Placement Errors. Part I: Limb Lead Reversals

    Directory of Open Access Journals (Sweden)

    Allison V. Rosen

    2015-10-01

    Full Text Available Background: Electrocardiography (ECG is a very useful diagnostic tool. However, errors in placement of ECG leads can create artifacts, mimic pathologies, and hinder proper ECG interpretation. It is important for members of the health care team to be able to recognize the common patterns resulting from lead placement errors. Methods: 12-lead ECGs were recorded in a single male healthy subject in his mid 20s. Six different limb lead reversals were compared to ECG recordings from correct lead placement. Results: Classic ECG patterns were observed when leads were reversed. Methods of discriminating these ECG patterns from true pathologic findings were described. Conclusion: Correct recording and interpretation of ECGs is key to providing optimal patient care. It is therefore crucial to be able to recognize common ECG patterns that are indicative of lead reversals.

  5. Lead tolerance in plants: strategies for phytoremediation.

    Science.gov (United States)

    Gupta, D K; Huang, H G; Corpas, F J

    2013-04-01

    Lead (Pb) is naturally occurring element whose distribution in the environment occurs because of its extensive use in paints, petrol, explosives, sludge, and industrial wastes. In plants, Pb uptake and translocation occurs, causing toxic effects resulting in decrease of biomass production. Commonly plants may prevent the toxic effect of heavy metals by induction of various celular mechanisms such as adsorption to the cell wall, compartmentation in vacuoles, enhancement of the active efflux, or induction of higher levels of metal chelates like a protein complex (metallothioneins and phytochelatins), organic (citrates), and inorganic (sulphides) complexes. Phyotochelains (PC) are synthesized from glutathione (GSH) and such synthesis is due to transpeptidation of γ-glutamyl cysteinyl dipeptides from GSH by the action of a constitutively present enzyme, PC synthase. Phytochelatin binds to Pb ions leading to sequestration of Pb ions in plants and thus serves as an important component of the detoxification mechanism in plants. At cellular level, Pb induces accumulation of reactive oxygen species (ROS), as a result of imbalanced ROS production and ROS scavenging processes by imposing oxidative stress. ROS include superoxide radical (O2(.-)), hydrogen peroxide (H2O2) and hydroxyl radical ((·)OH), which are necessary for the correct functioning of plants; however, in excess they caused damage to biomolecules, such as membrane lipids, proteins, and nucleic acids among others. To limit the detrimental impact of Pb, efficient strategies like phytoremediation are required. In this review, it will discuss recent advancement and potential application of plants for lead removal from the environment.

  6. potential for quality protein maize for reducing protein- energy

    African Journals Online (AJOL)

    ACSS

    social systems hampering QPM promotion and adoption and to identify ... affects growth and development. Protein- energy ... to purchase QPM seed leading to PEU reduction. Education ..... decision support framework “targetCSA”. Agricultural ...

  7. Both physiology and epidemiology support zero tolerable blood lead levels.

    Science.gov (United States)

    Shefa, Syeda T; Héroux, Paul

    2017-10-05

    Inorganic lead is one of the most common causes of environmental metal poisonings, and its adverse effects on multiple body systems are of great concern. The brain, along with the kidneys, are critically susceptible to lead toxicity for their hosting of high affinity lead binding proteins, and very sensitive physiology. Prolonged low-lead exposure frequently remains unrecognized, causes subtle changes in these organ systems, and manifests later at an irreversible stage. With the repeated documentation of "no safe blood lead level", the pernicious effects of lead at any measurable concentration need to be emphasized. In this review, we surveyed articles on chronic low-level lead exposures with a blood lead concentrations lead on both nervous and renal systems were obvious at a blood lead concentration of 2μg/dL, with the absence of any detectable threshold. The deleterious effect of lead on two different organ systems at such low concentrations drew our attention to the various extracellular and intracellular events that might be affected by minimal concentration of body lead, especially blood lead. Is there a true common ground between low-level lead toxicity in both the nervous system and the kidney? Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Lead user projects in practice

    DEFF Research Database (Denmark)

    Brem, Alexander; Gutstein, Adele

    2018-01-01

    Earlier research on the lead user method is focused on individual case studies and how the method was applied in a specific context. In this paper, we take a broader approach, analyzing a sample of 24 lead user projects, which included working with 188 lead users. These projects were analyzed...

  9. Lead poisoning in domestic ducks

    Energy Technology Data Exchange (ETDEWEB)

    Rac, R; Crisp, C S

    1954-05-01

    The death of wild ducks, due to the ingestion of lead shop, occurs frequently and is well documented. This paper discusses the death of domestic ducks due to the ingestion of lead. It describes the symptoms, and pathology of the lead poisoning of a clutch of 11 ducklings which were being raised on a farm in Australia. 3 references, 1 table.

  10. A study on lead equivalent

    International Nuclear Information System (INIS)

    Lin Guanxin

    1991-01-01

    A study on the rules in which the lead equivalent of lead glass changes with the energy of X rays or γ ray is described. The reason of this change is discussed and a new testing method of lead equivalent is suggested

  11. Lead- or Lead-bismuth-cooled fast reactors

    International Nuclear Information System (INIS)

    Bouchter, J.C.; Courouau, J.L.; Dufour, P.; Guidez, J.; Latge, C.; Martinelli, L.; Renault, C.; Rimpault, G.

    2014-01-01

    Lead-cooled fast reactors are one of the 6 concepts retained for the 4. generation of nuclear reactors. So far no lead-cooled reactors have existed in the world except lead-bismuth-cooled reactors in soviet submarines. Some problems linked to the use of the lead-bismuth eutectic appeared but were satisfactorily solved by a more rigorous monitoring of the chemistry of the lead-bismuth coolant. Lead presents various advantages as a coolant: no reactivity with water and the air,a high boiling temperature and low contamination when irradiated. The main asset of the lead-bismuth alloy is the drop of the fusion temperature from 327 C degrees to 125 C degrees. The main drawback of using lead (or lead-bismuth) is its high corrosiveness with metals like iron, chromium and nickel. The high corrosiveness of the coolant implies low flow velocities which means a bigger core and consequently a bigger reactor containment. Different research programs in the world (in Europe, Russia and the USA) are reviewed in the article but it appears that the development of this type of reactor requires technological breakthroughs concerning materials and the resistance to corrosion. Furthermore the concept of lead-cooled reactors seems to be associated to a range of low output power because of the compromise between the size of the reactor and its resistance to earthquakes. (A.C.)

  12. Electrical properties of a novel lead alkoxide precursor: Lead glycolate

    International Nuclear Information System (INIS)

    Tangboriboon, Nuchnapa; Pakdeewanishsukho, Kittikhun; Jamieson, Alexander; Sirivat, Anuvat; Wongkasemjit, Sujitra

    2006-01-01

    The reaction of lead acetate trihydrate Pb(CH 3 COO) 2 .3H 2 O and ethylene glycol, using triethylenetetramine (TETA) as a catalyst, provides in one step access to a polymer-like precursor of lead glycolate [-PbOCH 2 CH 2 O-]. On the basis of high-resolution mass spectroscopy, chemical analysis composition, FTIR, 13 C-solid state NMR and TGA, the lead glycolate precursor can be identified as a trimer structure. The FTIR spectrum demonstrates the characteristics of lead glycolate; the peaks at 1086 and 1042 cm -1 can be assigned to the C-O-Pb stretchings. The 13 C-solid state NMR spectrum gives notably only one peak at 68.639 ppm belonging to the ethylene glycol ligand. The phase transformations of lead glycolate and lead acetate trihydrate to lead oxide, their microstructures, and electrical properties were found to vary with increasing temperature. The lead glycolate precursor has superior electrical properties relative to those of lead acetate trihydrate, suggesting that the lead glycolate precursor can possibly be used as a starting material for producing electrical and semiconducting ceramics, viz. ferroelectric, anti-ferroelectric, and piezoelectric materials

  13. Current leads for superconducting magnets

    International Nuclear Information System (INIS)

    Ishibashi, Kenji

    1989-01-01

    Current leads for superconducting magnets have been studied since 1960's. The technology of current leads may seem to have been established both in theory and experiment before the middle of 1970's. Nevertheless, a wide variety of superconducting magnets have been introduced in the last 15 years, and the demands for special current leads have increased in accordance to the variety. A steady advance has been made in the design theory and fabrication of current leads. This paper describes the recent current lead technology regarding the design theory, safety in accidents, and high current capability. (author)

  14. 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.

  15. 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.

  16. Determination of Lead in Blood by Atomic Absorption Spectrophotometry1

    Science.gov (United States)

    Selander, Stig; Cramér, Kim

    1968-01-01

    Lead in blood was determined by atomic absorption spectrophotometry, using a wet ashing procedure and a procedure in which the proteins were precipitated with trichloroacetic acid. In both methods the lead was extracted into isobutylmethylketone before measurement, using ammonium pyrrolidine dithiocarbamate as chelator. The simpler precipitation procedure was shown to give results identical with those obtained with the ashing technique. In addition, blood specimens were examined by the precipitation method and by spectral analysis, which method includes wet ashing of the samples, with good agreement. All analyses were done on blood samples from `normal' persons or from lead-exposed workers, and no additions of inorganic lead were made. The relatively simple protein precipitation technique gave accurate results and is suitable for the large-scale control of lead-exposed workers. PMID:5663425

  17. Decontaminating lead bricks and shielding

    International Nuclear Information System (INIS)

    Lussiez, G.

    1994-01-01

    Lead used for shielding is often surface contaminated with radioisotopes and is therefore a RCRA D008 mixed waste. The technology-based standard for treatment is macroencapsulation. However, decontaminating and recycling the clean lead is a more attractive solution. Los Alamos National Laboratory decontaminates material and equipment contaminated with radioisotopes. Decontaminating lead poses special problems because of the RCRA hazard classification and the size of the inventory, now about 50 tons and likely to grow substantially of planned decommissioning operations. Thus lead, in the form of bricks and other shield shapes, is surface contaminated with fission products. One of the best methods for contaminated lead is removing the superficial layer of contamination with an abrasive medium under pressure. For lead, a mixture of alumina with water and air at about 40 psig rapidly and effectively decontaminates the lead. The abrasive medium is sprayed onto the lead in a scaled-off area. The slurry of abrasive and particles of lead falls through a floor and is collected in a sump. A pump sends the slurry mixture back to the spray gun, creating a continuous process. The process generates small volumes of lead slurry that can be solidified and, because it passes the TCLP, is not a mixed waste. The decontaminated lead can be released for recycling

  18. Decontaminating lead bricks and shielding

    International Nuclear Information System (INIS)

    Lussiez, G.W.

    1993-01-01

    Lead used for shielding is often surface contaminated with radioisotopes and is therefore a RCRA D008 mixed waste. The technology-based standard for treatment is macroencapsulation. However, decontaminating and recycling the clean lead is a more attractive solution. Los Alamos National Laboratory decontaminates material and equipment contaminated with radioisotopes. Decontaminating lead poses special problems because of the RCRA hazard classification and the size of the inventory, now about 50 tons and likely to grow substantially because of planned decommissioning operations. This lead, in the form of bricks and other shield shapes, is surface contaminated with fission products. One of the best methods for decontaminating lead is removing the thin superficial layer of contamination with an abrasive medium trader pressure. For lead, a mixture of alumina with water and air at about 40 psig rapidly and effectively decontaminates the lead. The abrasive medium is sprayed onto the lead in a sealed-off area. The slurry of abrasive and particles of lead falls through a floor grating and is collected in a sump. A pump sends the slurry mixture back to the spray gun, creating a continuous process. The process generates small volumes of contaminated lead slurry that can be solidified and, because it passes the TCLP, is not a mixed waste. The decontaminated lead can be released for recycling

  19. Involving Lead Users in Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Bilgram, Volker; Gutstein, Adele

    2018-01-01

    Research on the lead user method has been conducted for more than thirty years and has shown that the method is more likely to generate breakthrough innovation than traditional market research tools. Based on a systematic literature review, this paper shows a detailed view on the broad variety...... of research on lead user characteristics, lead user processes, lead user identification and application, and success factors. The main challenge of the lead user method as identified in literature is the resource issue regarding time, manpower, and costs. Also, internal acceptance and the processing...... of the method have been spotted in literature, as well as the intellectual property protection issue. From the starting point of the initial lead user method process introduced by Lüthje and Herstatt (2004), results are integrated into a revisited view on the lead user method process. In addition, concrete...

  20. Large-capacity current leads

    International Nuclear Information System (INIS)

    Ballarino, A.

    2008-01-01

    Feeding superconducting magnets with reliable low-loss devices is a key issue for any cryo-electrical system. Conventional or HTS current leads can be used, and cooling methods, materials, and geometries can be chosen to optimize the thermo-electrical performance of the system. The LHC magnets are powered via more than 3000 current leads transporting altogether about 3 MA of current. With thousands of leads, the LHC lead project represents today the largest project of its kind ever undertaken. Following a review of the LHC lead project, an overview of the choices that can be made for the optimization of large capacity current leads is presented. Examples are given of other leads for large scale magnet systems for which the use of HTS is being envisaged

  1. 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)

  2. Implications of protein polymorphism on protein phase behaviour

    NARCIS (Netherlands)

    Stegen, J.; Schoot, van der P.P.A.M.

    2015-01-01

    The phase behaviour of small globular proteins is often modeled by approximating them as spherical particles with fixed internal structure. However, changes in the local environment of a protein can lead to changes in its conformation rendering this approximation invalid. We present a simple

  3. Inactivation of Tor proteins affects the dynamics of endocytic proteins ...

    Indian Academy of Sciences (India)

    Tor2 is an activator of the Rom2/Rho1 pathway that regulates -factor internalization. Since the recruitment of endocytic proteins such as actin-binding proteins and the amphiphysins precedes the internalization of -factor, we hypothesized that loss of Tor function leads to an alteration in the dynamics of the endocytic ...

  4. Lead isotope ratios in artists' lead white: a progress report

    Energy Technology Data Exchange (ETDEWEB)

    Keisch, B; Callahan, R C [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA)

    1976-07-01

    The lead isotope ratios in over four hundred samples of lead white have been determined. The samples represent various geographical sources and dates from the thirteenth century to the present. A new method for organizing this large volume of data is described which helps with the visualization of temporal and geographic patterns. A number of interesting relationships between lead isotope ratio and date or source are shown to exist. Some examples of successful applications of this methodology are described.

  5. Lead isotope ratios in artists' lead white: a progress report

    International Nuclear Information System (INIS)

    Keisch, B.; Callahan, R.C.

    1976-01-01

    The lead isotope ratios in over four hundred samples of lead white have been determined. The samples represent various geographical sources and dates from the thirteenth century to the present. A new method for organizing this large volume of data is described which helps with the visualization of temporal and geographic patterns. A number of interesting relationships between lead isotope ratio and date or source are shown to exist. Some examples of successful applications of this methodology are described. (author)

  6. Synthesis of Lipidated Proteins.

    Science.gov (United States)

    Mejuch, Tom; Waldmann, Herbert

    2016-08-17

    Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

  7. Superconducting magnets and leads thereto

    International Nuclear Information System (INIS)

    Biltcliffe, M.N.; Hanley, P.E.; McKinnon, J.B.; Wheatley, R.W.

    1975-01-01

    The magnet described comprises a cryostat containing a superconducting coil for the generation of a magnetic field, with a short-circuiting superconducting link connected across the coil, and electrical leads extending through the cryostat to the coil; these leads are provided with joints within the cryostat to enable them to be detached from the coil and removed from the cryostat without interrupting the current through the coil, thus reducing heat conduction to the cryostat through the leads. The joints are arranged so that the leads can be readily detached and re-attached to the coil from outside the cryostat. Gas-tight seals are provided where the leads pass through the outer wall of the cryostat, with caps that can be secured after removal of the leads. This kind of magnet can provide a stable magnetic field continuously over long periods, such as is required in nuclear magnetic resonance spectrometers. (U.K.)

  8. 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

  9. 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.

  10. 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.

  11. Lead user projects in practice

    DEFF Research Database (Denmark)

    Brem, Alexander; Gutstein, Adele

    2018-01-01

    Earlier research on the lead user method is focused on individual case studies and how the method was applied in a specific context. In this paper, we take a broader approach, analyzing a sample of 24 lead user projects, which included working with 188 lead users. These projects were analyzed....... Moreover, crowdsourcing contests and netnography proved to be of significant value for the need, trend, and lead user identification phases. This paper concludes by discussing theoretical and practical implications, the limitations of this study, and recommendations for future studies....

  12. Decontaminating lead bricks and shielding

    International Nuclear Information System (INIS)

    Lussiez, G.W.

    1993-01-01

    Lead used for shielding is often surface contaminated with radionuclides and is therefore a Resource Conservation and Recovery Act (RCRA) D008 mixed waste. The technology-based standard for treatment is macroencapsulation. However, decontaminating and recycling the clean lead is a more attractive solution. Los Alamos National Lab. decontaminates material and equipment contaminated with radioisotopes. Decontaminating lead poses special problems because of the RCRA hazard classification and the size of the inventory, now about 100 metric tons and likely to grow substantially because of planned decommissioning operations. This lead, in the form of bricks and other shield shapes, is surface contaminated with fission products. One of the best methods for decontaminating lead is removing the thin superficial layer of contamination with an abrasive medium under pressure. For lead, a mixture of alumina with water and air at about 280 kPa (40 psig) rapidly and effectively decontaminates the lead. The abrasive medium is sprayed onto the lead in a sealed-off area. The slurry of abrasive and particles of lead falls through a floor grating and is collected in a pump. A pump sends the slurry mixture back to the spray gun, creating a continuous process

  13. Neurological aspects of lead intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Lehner, H

    1980-05-08

    This study gives a survey over the medical and scientific literature on lead intoxications, which were published until 1979. Neurologic aspects are of particular interest. At present dramatic cases of lead intoxications occur only rarely. However, there are numerous studies about cases of chronical, partly subclinical intoxications. This chronical type of lead intoxication can become manifest clinically as relatively vague symptoms, for example vertigos, insomnia, headaches and weakness. Contrary to this, serious encephalopathies, even with fatal outcome, and polyneuropathies with typical paresis of the radial nerve are preferably observed in acute lead intoxications. Besides the numerous sources of intoxication, also the different opinions found in literature are discussed, concerning the effects of lead on the human body. The fact that there are differing opinions about the limiting value of the blood-lead level at which intoxication symptoms have to be expected, becomes apparent when the determined blood-lead level values are compared and evaluated. Besides the description of general intoxication effects, the discussion of the neurologic aspects found in literature - not only those concerning the central, but also the peripheral system - are preferably concerned. Reports about neuropsychical alterations due to lead exposure, which are mainly found in children, supplement the numerous descriptions of the macroscopic and microscopic alterations of the nervous system provoked by lead. Finally the therapeutic and prophylactic measures given in the literature are discussed.

  14. Lead (Environmental Health Student Portal)

    Science.gov (United States)

    ... Air Pollution Home Indoor Air Pollution Outdoor Air Pollution Particulate Matter Ozone Chemicals Chemicals Home Mercury Lead Arsenic Volatile Organic Compounds Plastics Pesticides Climate Change ...

  15. Erythrocyte fluorescence and lead intoxication.

    Science.gov (United States)

    Clark, K G

    1976-01-01

    Blood samples from people exposed to inorganic lead were examined by fluorescence microscopy for excess erythrocyte porphyrin. With continued lead absorption, fluorescent erythrocytes appeared in the circulation of workers handling this metal or its compounds, and they progressively increased in number and brilliance. These changes ensued if the blood lead concentration was maintained above 2-42 mumol/l (50 mug/100 ml), and preceded any material fall in the haemoglobin value. At one factory, 62-5% of 81 symptomless workers showed erythrocyte fluorescence attributable to the toxic effects of lead. Excess fluorocytes were found in blood samples from a child with pica and three of her eight siblings. These four were subsequently shown to have slightly increased blood lead concentrations (2-03 to 2-32 mumol/l). Fluorescence microscopy for excess erythrocyte porphyrin is a sensitive method for the detection of chronic lead intoxication. A relatively slight increase in the blood lead is associated with demonstrabel changes in erythrocyte porphyrin content. The procedure requires little blood, and may be performed upon stored samples collected for lead estimation. The results are not readily influenced by contamination, and provide good confirmatory evidence for the absorption of biochemically active lead. PMID:963005

  16. 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),...

  17. 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.

  18. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  19. Proteins engineering

    International Nuclear Information System (INIS)

    2000-01-01

    At the - Departement d'Ingenierie et d'etudes de proteines (Deip) of the CEA more than seventy researchers are working hard to understand the function of proteins. For that they use the molecular labelling technique (F.M.)

  20. Whey Protein

    Science.gov (United States)

    ... reliable information about the safety of taking whey protein if you are pregnant or breast feeding. Stay on the safe side and avoid use. Milk allergy: If you are allergic to cow's milk, avoid using whey protein.

  1. In vivo x-ray fluorescence of bone lead in the study of human lead metabolism: Serum lead, whole blood lead, bone lead, and cumulative exposure

    International Nuclear Information System (INIS)

    Cake, K.M.; Chettle, D.R.; Webber, C.E.; Gordon, C.L.

    1995-01-01

    Traditionally, clinical studies of lead's effect on health have relied on blood lead levels to indicate lead exposure. However, this is unsatisfactory because blood lead levels have a half-life of approximately 5 weeks, and thus reflect recent exposure. Over 90% of the lead body burden is in bone, and it is thought to have a long residence time, thus implying that measurements of bone lead reflect cumulative exposure. So, measurements of bone lead are useful in understanding the long-term health effects of lead. Ahlgren reported the first noninvasive measurements of bone lead in humans, where γ-rays from 57 Co were used to excite the K series x-rays of lead. The lead detection system at McMaster University uses a 109 Cd source which is positioned at the center of the detector face (HPGe) and a near backscatter (∼160 degrees) geometry. This arrangement allows great flexibility, since one can sample lead in a range of different bone sites due to a robust normalization technique which eliminates the need to correct for bone geometry, thickness of overlying tissue, and other related factors. The effective radiation dose to an adult during an x-ray fluorescence bone lead measurement is extremely low, being 35 nSv. This paper addresses the issue of how bone, whole blood, and serum lead concentrations can be related in order to understand a person's lead exposure history

  2. Protein Polymers and Amyloids

    DEFF Research Database (Denmark)

    Risør, Michael Wulff

    2014-01-01

    Several human disorders are caused by a common general disease mechanism arising from abnormal folding and aggregation of the underlying protein. These include the prevalent dementias like Alzheimer’s and Parkinson’s, where accumulation of protein fibrillar structures, known as amyloid fibrils......, is a general hallmark. They also include the α1-antitrypsin deficiency, where disease-causing mutations in the serine protease inhibitor, α1-antitrypsin (α1AT), leads to accumulation of the aberrant protein in the liver of these patients. The native metastable structure of α1AT constitutes a molecular trap...... that inhibits its target protease through a large conformational change but mutations compromise this function and cause premature structural collapse into hyperstable polymers. Understanding the conformational disorders at a molecular level is not only important for our general knowledge on protein folding...

  3. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  4. Identification of proteins similar to AvrE type III effector proteins from ...

    African Journals Online (AJOL)

    Type III effector proteins are injected into host cells through type III secretion systems. Some effectors are similar to host proteins to promote pathogenicity, while others lead to the activation of disease resistance. We used partial least squares alignment-free bioinformatics methods to identify proteins similar to AvrE proteins ...

  5. Diffusion of Integral Membrane Proteins in Protein-Rich Membranes

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Metzler, Ralf

    2017-01-01

    of being protein-poor, native cell membranes are extremely crowded with proteins. On the basis of extensive molecular simulations, we here demonstrate that protein crowding of the membrane at physiological levels leads to deviations from the SD relation and to the emergence of a stronger Stokes......-like dependence D ∝ 1/R. We propose that this 1/R law mainly arises due to geometrical factors: smaller proteins are able to avoid confinement effects much better than their larger counterparts. The results highlight that the lateral dynamics in the crowded setting found in native membranes is radically different......The lateral diffusion of embedded proteins along lipid membranes in protein-poor conditions has been successfully described in terms of the Saffman-Delbrück (SD) model, which predicts that the protein diffusion coefficient D is weakly dependent on its radius R as D ∝ ln(1/R). However, instead...

  6. 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.

  7. Lead poisoning from souvenir earthenware.

    Science.gov (United States)

    Hellström-Lindberg, Eva; Björklund, Andreas; Karlson-Stiber, Christine; Harper, Pauline; Seldén, Anders I

    2006-02-01

    A case of massive lead poisoning from juice contained in a Greek earthenware jug as well as six satellite cases of high lead exposure of similar origin is reported. The intoxicated patient was successfully treated with dimercaptosuccinic acid. Ceramic producers should adhere to the longstanding European legislation.

  8. 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.

  9. 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 ...

  10. Photocatalyzed removal of lead ion from lead-chelator solution

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Hyun; Na, Jung Won; Sung, Ki Woung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-07-01

    The present study was undertaken to examine the influence of such chelating agents on the ease and speed of photocatalyzed metal removal and deposition. With excess EDTA, the free EDTA competes with Pb for oxidation, and at a ten fold excess, no lead oxidation (hence removal) occurs. With insufficient EDTA, the corresponding initial concentration of Pb-EDTA is decreased; after its destruction, the remaining Pb{sup 2+} is removed more slowly, at rates found with lead nitrate solution. The net result is that the maximum rate of lead deposition occurs at the stoichiometric ratio of 1:1 EDTA : Pb{sup 2+}.

  11. Distribution of lead in teeth

    Energy Technology Data Exchange (ETDEWEB)

    Fremlin, J H; Tanti-Wipawin, W [Birmingham Univ. (UK). Dept. of Physics

    1976-07-01

    There is currently much concern with the amount of lead in the environment. Measurement of lead in teeth is being used to give information on the integrated uptake of lead by the individual over a period. The distribution of lead within individual teeth, is examined with the object of distinguishing lead deposited during formation or calcification from that taken up by the tooth over its working life after eruption. A tooth is sectioned and bombarded with 30-MeV ions of helium-3 from the Birmingham 1.52-m cyclotron, which produces polonium isotopes. The main useful activity is due to polonium-206, an ..cap alpha.. emitter, half-life 8 d. These ..cap alpha.. particles can be recorded by a plastic solid-state track detector.

  12. Distribution of lead in teeth

    International Nuclear Information System (INIS)

    Fremlin, J.H.; Tanti-Wipawin, W.

    1976-01-01

    There is currently much concern with the amount of lead in the environment. Measurement of lead in teeth is being used to give information on the integrated uptake of lead by the individual over a period. The distribution of lead within individual teeth, is examined with the object of distinguishing lead deposited during formation or calcification from that taken up by the tooth over its working life after eruption. A tooth is sectioned and bombarded with 30-MeV ions of helium-3 from the Birmingham 1.52-m cyclotron, which produces polonium isotopes. The main useful activity is due to polonium-206, an α emitter, half-life 8 d. These α particles can be recorded by a plastic solid-state track detector. (U.K.)

  13. 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.

  14. Environmental lead hazard to children.

    Science.gov (United States)

    Mittal, S K

    1992-01-01

    Clinically evident lead poisoning is rare in Indian children but is more common than in adults. In children, lead poisoning may appear as fever, seizures, anemia, or abdominal pain, while in adults it is more likely to manifest as chronic minor peripheral neuropathy or gum pigmentation. Children with acute lead poisoning can be treated with chelators such as EDTA and BAL, but many are left with permanent brain damage. The most common sources of acute lead poisoning in Indian children are inhalation of fumes from burned car batteries, ingestion of flaking paint, consuming food cooked in cheap aluminum or brass utensils, and eating contaminated soil. The sources of chronic lead poisoning are water from lead pipes and fumes from industrial or automotive exhaust. Another common source in India is application of "kajjal" to children's eyes. Sources of lead in Western countries, such as drinking water, canned food, residential paint, automotive fuel, and ambient air quality, are regulated by law. None of these are regulated in India.

  15. Yeast Interacting Proteins Database: YDL239C, YDR273W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...it as prey (1) YDR273W DON1 Meiosis-specific component of the spindle pole body, part of the leading... edge protein (LEP) coat, forms a ring-like structure at the leading edge of the prospore...ption Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading...description Meiosis-specific component of the spindle pole body, part of the leading edge protein (LEP) coat

  16. Water quality criteria for lead

    Energy Technology Data Exchange (ETDEWEB)

    Nagpal, N.K.

    1987-01-01

    This report is one in a series that establishes water quality criteria for British Columbia. The report sets criteria for lead to protect a number of water uses, including drinking water, freshwater and marine aquatic life, wildlife, livestock, irrigation, and recreation. The criteria are set as either maximum concentrations of total lead that should not be exceeded at any time, or average concentrations that should not be exceeded over a 30-day period. Actual values are summarized.

  17. Chronic lead intoxication in calves

    Energy Technology Data Exchange (ETDEWEB)

    Wagenaar, G

    1963-01-01

    Four calves born in the winter of 1961-1962 died on a farm after a disease which had run its course for periods ranging from six weeks to a few months. A calf had also died showing similar symptoms during the previous year. All calves showed identical symptoms. Initially, their liveliness diminished; subsequently, they drank less and showed signs of pica. They finally died after the disease had run its course for about six weeks. The last calf, born late in February 1962, was in poor health as early as May, improved slightly when it had been sent out to grass but died in September, having fallen ill again in August. Autopsy was performed on three calves; all three were affected with chronic interstitial nephritis and uraemic endocarditis of the left auricle was present as well. The results obtained on toxicological investigation were indicative of lead poisoning. The liver of the calf was found to contain two mg of lead per kg, the cortex of the kidney containing twenty-five mg of lead per kg. These figures did not provide direct evidence of lead poisoning, but in evaluating these figures the fact was taken into account that the calf had no longer been able to ingest any lead for several months. Meanwhile, it was found that the stock-owner had fitted an old painted door in the calf-shed, which door was constantly being licked by the calves. The paint contained 18.6% of lead. This finding was followed by examination of the liver of a calf that had died previously. It was found to contain 49.7 mg of lead per kg. Accordingly, the calves had been affected with a form of lead poisoning running a relatively slow course, as a result of which the animals had developed chronic interstitial nephritis. The calves eventually died from uraemia. 4 references.

  18. The biology of non-native proteins

    NARCIS (Netherlands)

    Herczenik, E.

    2007-01-01

    Protein misfolding diseases are linked by common principles of protein aggregation, plaque development and tissue damage. There is no adequate therapy for these highly debilitating diseases. This thesis aims to increase the understanding of protein misfolding diseases, which will hopefully lead to

  19. Protein-protein interactions and cancer: targeting the central dogma.

    Science.gov (United States)

    Garner, Amanda L; Janda, Kim D

    2011-01-01

    Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

  20. Protein Adsorption in Three Dimensions

    Science.gov (United States)

    Vogler, Erwin A.

    2011-01-01

    initially-adsorbed protein. Interphase protein concentration CI increases as VI decreases, resulting in slow reduction in interfacial energetics. Steady-state is governed by a net partition coefficient P=(/CBCI). In the process of occupying space within the interphase, adsorbing protein molecules must displace an equivalent volume of interphase water. Interphase water is itself associated with surface-bound water through a network of transient hydrogen bonds. Displacement of interphase water thus requires an amount of energy that depends on the adsorbent surface chemistry/energy. This “adsorption-dehydration” step is the significant free-energy cost of adsorption that controls the maximum amount of protein that can be adsorbed at steady state to a unit adsorbent-surface area (the adsorbent capacity). As adsorbent hydrophilicity increases, protein adsorption monotonically decreases because the energetic cost of surface dehydration increases, ultimately leading to no protein adsorption near an adsorbent water wettability (surface energy) characterized by a water contact angle θ → 65°. Consequently, protein does not adsorb (accumulate at interphase concentrations greater than bulk solution) to more hydrophilic adsorbents exhibiting θ protein/surface interactions can be highly favorable, causing protein to adsorb in multilayers in a relatively thick interphase. A straightforward, three-component free energy relationship captures salient features of protein adsorption to all surfaces predicting that the overall free energy of protein adsorption ΔGadso is a relatively small multiple of thermal energy for any surface chemistry (except perhaps for bioengineered surfaces bearing specific ligands for adsorbing protein) because a surface chemistry that interacts chemically with proteins must also interact with water through hydrogen bonding. In this way, water moderates protein adsorption to any surface by competing with adsorbing protein molecules. This Leading Opinion ends

  1. Delivery of the autofluorescent protein R-phycoerythrin by calcium phosphate nanoparticles into four different eukaryotic cell lines (HeLa, HEK293T, MG-63, MC3T3): Highly efficient, but leading to endolysosomal proteolysis in HeLa and MC3T3 cells.

    Science.gov (United States)

    Kopp, Mathis; Rotan, Olga; Papadopoulos, Chrisovalantis; Schulze, Nina; Meyer, Hemmo; Epple, Matthias

    2017-01-01

    Nanoparticles can be used as carriers to transport biomolecules like proteins and synthetic molecules across the cell membrane because many molecules are not able to cross the cell membrane on their own. The uptake of nanoparticles together with their cargo typically occurs via endocytosis, raising concerns about the possible degradation of the cargo in the endolysosomal system. As the tracking of a dye-labelled protein during cellular uptake and processing is not indicative of the presence of the protein itself but only for the fluorescent label, a label-free tracking was performed with the red-fluorescing model protein R-phycoerythrin (R-PE). Four different eukaryotic cell lines were investigated: HeLa, HEK293T, MG-63, and MC3T3. Alone, the protein was not taken up by any cell line; only with the help of calcium phosphate nanoparticles, an efficient uptake occurred. After the uptake into HeLa cells, the protein was found in early endosomes (shown by the marker EEA1) and lysosomes (shown by the marker Lamp1). There, it was still intact and functional (i.e. properly folded) as its red fluorescence was detected. However, a few hours after the uptake, proteolysis started as indicated by the decreasing red fluorescence intensity in the case of HeLa and MC3T3 cells. 12 h after the uptake, the protein was almost completely degraded in HeLa cells and MC3T3 cells. In HEK293T cells and MG-63 cells, no degradation of the protein was observed. In the presence of Bafilomycin A1, an inhibitor of acidification and protein degradation in lysosomes, the fluorescence of R-PE remained intact over the whole observation period in the four cell lines. These results indicate that despite an efficient nanoparticle-mediated uptake of proteins by cells, a rapid endolysosomal degradation may prevent the desired (e.g. therapeutic) effect of a protein inside a cell.

  2. Lead isotope in mineral exploration

    International Nuclear Information System (INIS)

    Gulson, B.L.

    1986-01-01

    This book provides an up-to-date state-of-the-art review of lead isotopes in mineral exploration. Beginning with an historical review on suggested uses of lead isotopes in mineral exploration, the author then outlines the theoretical aspects of lead isotopes and illustrates that the method is based on well-known principles of radioactive decay, from which isotopic signatures for different styles of mineralization are derived. The varying isotopic signatures are then introduced. The major part of the book details over 40 case histories for base and precious metals, uranium and tin using sampling media such as sulfides, gossans, soils, weathered bedrock, vegetation and groundwaters. Advantages and disadvantages of each are discussed. Examples are given of the use of lead isotopes in testing conceptual models for exploration. The success rate and cost-effectiveness of the method are illustrated by actual exploration examples. Analytical advances which should lower the cost of the method and future uses are outlined. Many of the case histories use recently published or unpublished data, 27 tables of which are given in an appendix. Details of sampling, the methods for obtaining the isotope ratios, and a commercially-available integrated lead isotope service are also provided. (Auth.)

  3. Lead poisoning after gunshot wound

    Directory of Open Access Journals (Sweden)

    Paulo Roberto de Madureira

    2000-05-01

    Full Text Available CONTEXT: Despite the absence of symptoms in the majority of patients carrying lead bullet fragments in their bodies, there needs to be an awareness of the possible signs and symptoms of lead intoxication when bullets are lodged in large joints like knees, hips and shoulders. Such patients merit closer follow-up, and even surgical procedure for removing the fragments. OBJECTIVE: To describe a patient who developed clinical lead intoxication several years after a gunshot wound. DESIGN: Case report. CASE REPORT: A single white 23-year-old male, regular job as a bricklayer, with a history of chronic alcohol abuse, showed up at the emergency department complaining of abdominal pain with colic, weakness, vomiting and diarrhea with black feces. All the symptoms had a duration of two to three weeks, and had been recurrent for the last two years, with calming during interval periods of two to three weeks. Abdominal radiograms showed a bullet lodged in the left hip, with a neat bursogram of the whole synovial capsule. A course of chelating treatment using calcium versenate (EDTACaNa2 intravenously was started. After the chelation therapy the patient had recurrence of his symptoms and a radical solution for the chronic mobilization of lead was considered. A hip arthroplasty procedure was performed, leading to complete substitution of the left hip.

  4. Lead and Hyperactivity: Lead Levels Among Hyperactive Children

    Science.gov (United States)

    David, Oliver J.; And Others

    1977-01-01

    In the study it is shown that within a group of 84 hyperactive children (4 to 11 years old) those for whom an organic etiology is present have lead burdens lower than in those for whom no apparent cause could be found. (Author/SBH)

  5. Protein politics

    NARCIS (Netherlands)

    Vijver, Marike

    2005-01-01

    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and

  6. Protein adhesives

    Science.gov (United States)

    Charles R. Frihart; Linda F. Lorenz

    2018-01-01

    Nature uses a wide variety of chemicals for providing adhesion internally (e.g., cell to cell) and externally (e.g., mussels to ships and piers). This adhesive bonding is chemically and mechanically complex, involving a variety of proteins, carbohydrates, and other compounds.Consequently,the effect of protein structures on adhesive properties is only partially...

  7. Microcirculation in experimental lead poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Fimiani, R; Silvestroni, A; Iavicoli, N

    1973-01-01

    A study was made of the microvascular system of the auricle of the ear in 15 rabbits to which a 10 percent solution of lead acetate (0.5cm/sup 3//kg) was administered daily for 15 days through the gastric tract. Every 5 days up to the 35th day, determinations of blood and urine lead, free erythrocyte protoporphyrins and urinary coproporphyrins were carried out. Observations of the microvascular system were carried out in basic conditions after 6, 11, 16, 26 and 36 days. On the 6th day there was no pathological finding; on the 11th day small changes of the vascular content were observed, progressively assuming a sludge-like aspect. These findings confirm the hypothesis that the earliest changes caused by lead appear in the vascular content, before parietal changes occur.

  8. Jet calculus beyond leading logarithms

    International Nuclear Information System (INIS)

    Kalinowski, J.; Konishi, K.; Taylor, T.R.

    1981-01-01

    It is shown that the evolution of hadronic jets produced in hard processes can be studied in terms of a simple parton branching picture, beyond the leading log approximation of QCD. The jet calculus is generalized to any given order of logs (but always to all orders of αsub(s)). We discuss the general structure of the formalism. Universality of jet evolution is discussed. We consider also a jet calorimetry measure and the multiplicity distribution of final states in a form which allows a systematic improvement of approximation. To the next-to-leading order, we prove the finiteness and elucidate the scheme dependence of parton subprocess probabilities. The physical inclusive cross section is shown to be scheme independent: next-to-leading results for e + e - → q (nonsinglet) + X agree with those of Curci and others. (orig.)

  9. Initial occupational exposure to lead

    Energy Technology Data Exchange (ETDEWEB)

    Forni, A.; Cambiaghi, G.; Secchi, G.C.

    1976-01-01

    Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50 percent of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study.

  10. Occupational protein contact dermatitis.

    Science.gov (United States)

    Barbaud, Annick; Poreaux, Claire; Penven, Emmanuelle; Waton, Julie

    2015-01-01

    Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

  11. Chronic lead intoxication; Chronische Bleiintoxikation

    Energy Technology Data Exchange (ETDEWEB)

    Wieseler, B.; Leng, G. [Duesseldorf Univ. (Germany). Inst. fuer Hygiene; Lenz, S.; Schultz, C. [Klinikum Remscheid GmbH, Remscheid (Germany); Wilhelm, M. [Bochum Univ. (Germany). Inst. fuer Hygiene, Sozial- und Umweltmedizin

    1999-02-01

    The case of a female 68 years old patient is described. Here, a chronic lead intoxication was diagnosed after a two year old medical history with increasing attacks of colic-like abdominal pain often described as life-threatening. After repeated hospitalizations and intensive search for the cause of the symptoms, porphyria and anemia was found to be a sign of a chronic lead poisoning. The blood lead concentrations were always about a level of 600 {mu}g/L. The source of exposure could not be found by now. Neither home inspection nor environmental investigations have shown a recent source of lead intake by the patient. However, a possible occupational source of lead exposure at a blast furnace was established by anamnesis for 1952 to 1962. Thus, osteoporosis induced lead mobilisation was suspected. Noticeable are the results of the six abdominal survey radiographies taken during hospitalization within one year; three radiographies were taken following clinical admission and three before discharge of the patient. In comparison, the course shows a chronic relapsing alimentary supply from metallic particles of unknown genesis. The patient was treated with the sodium salt of 2,3-dimercapto-1-propansulfonic acid (DMPS, Dimaval{sup TM}). She was free of complain afterwards. Following therapy, the blood lead concentrations fell under a level of 400 {mu}m/L, but after several weeks the lead level raised up to the original level of 600 {mu}g/L. (orig.) [Deutsch] Es wird eine 68jaehrige Patientin vorgestellt, bei der nach fast zweijaehriger Krankengeschichte, die gekennzeichnet war durch rezidivierende, teils als lebensbedrohlich geschilderte Bauchkoliken, eine chronische Bleiintoxikation diagnostiziert wurde. Erst nach wiederholten stationaeren Krankenhausaufenthalten mit intensiver Suche nach der Krankheitsursache wurden das Krankheitsbild und die Laborwerte durch Zusatzuntersuchungen ergaenzt, so dass sich in der festgestellten Porphyrie und Anaemie die Diagnose der

  12. Deformation properties of lead isotopes

    International Nuclear Information System (INIS)

    Tolokonnikov, S. V.; Borzov, I. N.; Lutostansky, Yu. S.; Saperstein, E. E.

    2016-01-01

    The deformation properties of a long lead isotopic chain up to the neutron drip line are analyzed on the basis of the energy density functional (EDF) in the FaNDF 0 Fayans form. The question of whether the ground state of neutron-deficient lead isotopes can have a stable deformation is studied in detail. The prediction of this deformation is contained in the results obtained on the basis of the HFB-17 and HFB-27 Skyrme EDF versions and reported on Internet. The present analysis reveals that this is at odds with experimental data on charge radii and magnetic moments of odd lead isotopes. The Fayans EDF version predicts a spherical ground state for all light lead isotopes, but some of them (for example, 180 Pb and 184 Pb) prove to be very soft—that is, close to the point of a phase transition to a deformed state. Also, the results obtained in our present study are compared with the predictions of some other Skyrme EDF versions, including SKM*, SLy4, SLy6, and UNE1. By and large, their predictions are closer to the results arising upon the application of the Fayans functional. For example, the SLy4 functional predicts, in just the same way as the FaNDF 0 functional, a spherical shape for all nuclei of this region. The remaining three Skyrme EDF versions lead to a deformation of some light lead isotopes, but their number is substantially smaller than that in the case of the HFB-17 and HFB-27 functionals. Moreover, the respective deformation energy is substantially lower, which gives grounds to hope for the restoration of a spherical shape upon going beyond the mean-field approximation, which we use here. Also, the deformation properties of neutron-rich lead isotopes are studied up to the neutron drip line. Here, the results obtained with the FaNDF 0 functional are compared with the predictions of the HFB-17, HFB-27, SKM*, and SLy4 Skyrme EDF versions. All of the EDF versions considered here predict the existence of a region where neutron-rich lead isotopes undergo

  13. Mortality study of lead workers

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, W C; Gaffey, W R

    1975-01-01

    The mortality of 7,032 men employed for one or more years in lead production facilities or battery plants was followed over a 23-year period, 1947-70. Lead absorption in many of these men was greatly in excess of currently accepted standards based upon urinary and blood lead concentrations available for a portion of the group. There were 1,356 deaths reported. The standardized mortality ratio (SMR) for all causes was 107 for smelter workers and 99 for battery plant workers. Death from neoplasms were in slight excess in smelters, but not significantly increased in battery plants. There were no excess deaths from kidney tumors. The SMR for cardiovascular-renal disease was 96 for smelter workers and 101 for battery plant workers. There was definitely no excess in deaths from either stroke or hypertensive heart disease; however, deaths classified as other hypertensive disease and unspecified nephritis or renal sclerosis were higher than expected. The life expectancy of lead workers was calculated to be approximately the same as that of all U.S. males.

  14. High temperature superconductor current leads

    International Nuclear Information System (INIS)

    Zeimetz, B.; Liu, H.K.; Dou, S.X.

    1996-01-01

    Full text: The use of superconductors in high electrical current applications (magnets, transformers, generators etc.) usually requires cooling with liquid Helium, which is very expensive. The superconductor itself produces no heat, and the design of Helium dewars is very advanced. Therefore most of the heat loss, i.e. Helium consumption, comes from the current lead which connects the superconductor with its power source at room temperature. The current lead usually consists of a pair of thick copper wires. The discovery of the High Temperature Superconductors makes it possible to replace a part of the copper with superconducting material. This drastically reduces the heat losses because a) the superconductor generates no resistive heat and b) it is a very poor thermal conductor compared with the copper. In this work silver-sheathed superconducting tapes are used as current lead components. The work comprises both the production of the tapes and the overall design of the leads, in order to a) maximize the current capacity ('critical current') of the superconductor, b) minimize the thermal conductivity of the silver clad, and c) optimize the cooling conditions

  15. Lead apron: room for improvement

    Energy Technology Data Exchange (ETDEWEB)

    Boothroyd, A.E.; Russell, J.G.B.

    1987-02-01

    The amount of red bone marrow not protected by a lead apron was used as an assessment of protection efficiency, and the effect of change of shape was calculated. It was concluded that change of shape would increase protection and cut down cost. (U.K.).

  16. OPAL Various Lead Glass Blocks

    CERN Multimedia

    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.

  17. Copper, lead and zinc production

    International Nuclear Information System (INIS)

    Ayers, J.; Ternan, S.

    2001-01-01

    This chapter provides information on the by-products and residues generated during the production of copper, lead and zinc. The purpose of this chapter is to describe by-products and residues which are generated, how these may be avoided or minimised, and available options for the utilization and management of residues. (author)

  18. Lead-iron phosophate glass

    International Nuclear Information System (INIS)

    Sales, B.C.; Boatner, L.A.

    1988-01-01

    The lead-iron phosphate nuclear waste glasses (LIPNWG) are the subject of the present chapter. They were discovered in 1984 while the authors were attempting to find a sintering aid for certain types of crystalline monazite ceramic high-level nuclear waste forms. In the present chapter, the term waste glass is synonymous with nuclear waste glass (NWG), and the acronym LIP is often used for lead-iron phosphate. Lead-iron phosphate glasses, like many of the previously studied phosphate glasses, are corrosion resistant in aqueous solutions at temperatures below 100 degrees C, and they can be melted and poured at temperatures that are relatively low in comparison with the processing temperatures required for current silicate glass compositions. Unlike the phosphate glasses investigated previously, however, LIPNWGs do not suffer from alteration due to devitrification during realistic and readily, achievable cooling periods. Additionally, lead-iron phosphate glass melts are not nearly as corrosive as the sodium phosphate melts investigated during the 1960s; and, therefore, they can be melted and processed using crucibles made from a variety of materials

  19. Current Leads, Links and Buses

    CERN Document Server

    Ballarino, A

    2014-01-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  20. Triplet states in lead isotopes

    International Nuclear Information System (INIS)

    Naz, Tabassum; Ahmad, Shakeb; Abusara, H.

    2017-01-01

    Axial and triaxial calculations within RHB have been done to study the shape coexistence phenomena in the lead isotopes. Triplet states have been found in the 184-190 Pb which are in accordance with the experimental and other theoretical observations. The energy difference (in MeV) between the first two excited states also gives the evidence for the same

  1. Implementation Guide: Leading School Change

    Science.gov (United States)

    Whitaker, Todd

    2010-01-01

    This two-part "Implementation Guide" will help to deepen your understanding and sharpen your ability to implement each of the strategies discussed in "Leading School Change: Nine Strategies to Bring Everybody on Board" (ED509821). Part One offers discussion questions and activities which focus on each of the nine strategies. They can be completed…

  2. 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)

  3. 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...

  4. Current Leads, Links and Buses

    Energy Technology Data Exchange (ETDEWEB)

    Ballarino, A [European Organization for Nuclear Research, Geneva (Switzerland)

    2014-07-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  5. 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…

  6. Effects of occupational lead exposure.

    Science.gov (United States)

    Wang, Y L; Lu, P K; Chen, Z Q; Liang, Y X; Lu, Q M; Pan, Z Q; Shao, M

    1985-01-01

    Fifty-three workers in a battery factory, 52 solderers in a television factory, and 50 embroidery workers (a reference group) were studied. The average air lead levels of the three workplaces were 0.578 mg/m3, 0.002 mg/m3, and 0.001 mg/m3, respectively. Adverse effects in terms of clinical manifestations and biochemical criteria were evident among the battery factory workers. A significant dose-response relationship existed between the toxic effects and the air lead levels. The solderers showed no apparent abnormalities in comparison with the embroidery workers. The early clinical manifestations were dysfunction of the central nervous system, indigestion, arthralgia, and myalgia in the extremities. A positive association was observed between the prevalence of fatigue, mild abdominal pain, and arthralgia and the blood lead (PbB), urinary lead (PbU), and zinc protoporphyrin (ZPP) levels. The symptomatic threshold values of PbB, PbU, and ZPP were 30 micrograms/dl (1.5 mumol/l), 0.045 mg/l (0.2 mumol/l), and 40 micrograms/dl (0.7 mumol/l), respectively. The PbB, PbU, free erythrocyte protoporphyrin, and ZPP levels and the blood aminolevulinic dehydratase ratio could be used as indicators of lead exposure, although ZPP is preferred for a preventive monitoring program. The motor and sensory conduction velocities of the median nerve were slower in the exposed groups than in the reference group. No effects on behavioral function were observed among the solderers.

  7. Gammatography of thick lead vessels

    International Nuclear Information System (INIS)

    Raghunath, V.M.; Bhatnagar, P.K.; Sundaram, V.M.

    1979-01-01

    Radiography, scintillation and GM counting and dose measurements using ionisation chamber equipment are commonly used for detecting flaws/voids in materials. The first method is mostly used for steel vessels and to a lesser extent thin lead vessels also and is essentially qualitative. Dose measuring techniques are used for very thick and large lead vessels for which high strength radioactive sources are required, with its inherent handling problems. For vessels of intermediate thicknesses, it is ideal to use a small strength source and a GM or scintillation counter assembly. At the Reactor Research Centre, Kalpakkam, such a system was used for checking three lead vessels of thicknesses varying from 38mm to 65mm. The tolerances specified were +- 4% variation in lead thickness. The measurements also revealed the non concentricity of one vessel which had a thickness varying from 38mm to 44mm. The second vessel was patently non-concentric and the dimensional variation was truly reproduced in the measurements. A third vessel was fabricated with careful control of dimensions and the measurements exhibited good concentricity. Small deviations were observed, attributable to imperfect bondings between steel and lead. This technique has the following advantages: (a) weaker sources used result in less handling problems reducing the personnel exposures considerably; (b) the sensitivity of the instrument is quite good because of better statistics; (c) the time required for scanning a small vessel is more, but a judicious use of a scintillometer for initial fast scan will help in reducing the total scanning time; (d) this method can take advantage of the dimensional variations themselves to get the calibration and to estimate the deviations from specified tolerances. (auth.)

  8. Deaths: Leading Causes for 2011.

    Science.gov (United States)

    Heron, Melonie

    2015-07-27

    This report presents final 2011 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements ‘‘Deaths: Final Data for 2011,’’ the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2011. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2011, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2011 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission

  9. Deaths: Leading Causes for 2015.

    Science.gov (United States)

    Heron, Melonie

    2017-11-01

    Objectives-This report presents final 2015 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2015," the National Center for Health Statistics' annual report of final mortality statistics. Methods-Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2015. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. Results-In 2015, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2015 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without

  10. Deaths: leading causes for 2010.

    Science.gov (United States)

    Heron, Melonie

    2013-12-20

    This report presents final 2010 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2010. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2010, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Nephritis, nephrotic syndrome and nephrosis; Influenza and pneumonia; and Intentional self-harm (suicide). These 10 causes accounted for 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2010 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and post-neonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source

  11. Deaths: Leading Causes for 2013.

    Science.gov (United States)

    Heron, Melonie

    2016-02-16

    This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as

  12. Deaths: Leading Causes for 2012.

    Science.gov (United States)

    Heron, Melonie

    2015-08-31

    This report presents final 2012 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2012," the National Center for Health Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2012. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2012, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2012 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  13. Proatherogenic pathways leading to vascular calcification

    International Nuclear Information System (INIS)

    Mazzini, Michael J.; Schulze, P. Christian

    2006-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

  14. Prions and prion-like proteins.

    Science.gov (United States)

    Fraser, Paul E

    2014-07-18

    Prions are self-replicating protein aggregates and are the primary causative factor in a number of neurological diseases in mammals. The prion protein (PrP) undergoes a conformational transformation leading to aggregation into an infectious cellular pathogen. Prion-like protein spreading and transmission of aggregates between cells have also been demonstrated for other proteins associated with Alzheimer disease and Parkinson disease. This protein-only phenomenon may therefore have broader implications in neurodegenerative disorders. The minireviews in this thematic series highlight the recent advances in prion biology and the roles these unique proteins play in disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. 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 ...

  16. Controlling proteins through molecular springs.

    Science.gov (United States)

    Zocchi, Giovanni

    2009-01-01

    We argue that the mechanical control of proteins-the notion of controlling chemical reactions and processes by mechanics-is conceptually interesting. We give a brief review of the main accomplishments so far, leading to our present approach of using DNA molecular springs to exert controlled stresses on proteins. Our focus is on the physical principles that underlie both artificial mechanochemical devices and natural mechanisms of allostery.

  17. Laser-assisted lead extraction: the European experience.

    Science.gov (United States)

    Kennergren, C; Bucknall, C A; Butter, C; Charles, R; Fuhrer, J; Grosfeld, M; Tavernier, R; Morgado, T B; Mortensen, P; Paul, V; Richter, P; Schwartz, T; Wellens, F

    2007-08-01

    The aim of this study is to investigate the safety and effectiveness of Excimer laser-assisted lead extraction in Europe. The final European multi-centre study experience is presented. The Excimer is a cool cutting laser (50 degrees C) with a wavelength of 308 nm. The energy is emitted from the tip of a flexible sheath and is absorbed by proteins and lipids, 64% of the energy is absorbed at a tissue depth of 0.06 mm. The sheath is positioned over the lead, and the fibrosis surrounding the lead is vaporized while advancing the sheath without damaging other leads. From August 1996 to March 2001, 383 leads (170 atrial, 213 ventricular) in 292 patients (mean age 61.6 years, range 13-96) were extracted at 14 European centres. Mean implantation time was 74 months (3-358). Most frequent indications were pocket infection (26%), non-functional leads (21%), patient morbidity (21%), septicaemia or endocarditis (14%), erosion (5%), and lead interference (8%). Median extraction time was 15 min (1-300). Complete extraction was achieved in 90.9% of the leads and partial extraction in 3.4%. Extraction failed in 5.7% of the leads. Major complications = perforations caused 10/22 (3.4/5.7%) of the failures. Most partially extracted patients were considered clinically successful, as only minor lead parts without clinical significance were left. Femoral non-laser technique was used to remove 8/12 of the non-complication failures. The total complication rate, including five minor complications (1.7%), was 5.1%. No in-hospital mortality occurred. Pacing and implantable cardioverter-defibrillator leads can safely, effectively, and predictably be extracted. Open-heart extractions can be limited to special cases. The results indicate that the traditional policy of abandoning redundant leads, instead of removing them, may be obsolete in many patients.

  18. Delivery of the autofluorescent protein R-phycoerythrin by calcium phosphate nanoparticles into four different eukaryotic cell lines (HeLa, HEK293T, MG-63, MC3T3: Highly efficient, but leading to endolysosomal proteolysis in HeLa and MC3T3 cells.

    Directory of Open Access Journals (Sweden)

    Mathis Kopp

    Full Text Available Nanoparticles can be used as carriers to transport biomolecules like proteins and synthetic molecules across the cell membrane because many molecules are not able to cross the cell membrane on their own. The uptake of nanoparticles together with their cargo typically occurs via endocytosis, raising concerns about the possible degradation of the cargo in the endolysosomal system. As the tracking of a dye-labelled protein during cellular uptake and processing is not indicative of the presence of the protein itself but only for the fluorescent label, a label-free tracking was performed with the red-fluorescing model protein R-phycoerythrin (R-PE. Four different eukaryotic cell lines were investigated: HeLa, HEK293T, MG-63, and MC3T3. Alone, the protein was not taken up by any cell line; only with the help of calcium phosphate nanoparticles, an efficient uptake occurred. After the uptake into HeLa cells, the protein was found in early endosomes (shown by the marker EEA1 and lysosomes (shown by the marker Lamp1. There, it was still intact and functional (i.e. properly folded as its red fluorescence was detected. However, a few hours after the uptake, proteolysis started as indicated by the decreasing red fluorescence intensity in the case of HeLa and MC3T3 cells. 12 h after the uptake, the protein was almost completely degraded in HeLa cells and MC3T3 cells. In HEK293T cells and MG-63 cells, no degradation of the protein was observed. In the presence of Bafilomycin A1, an inhibitor of acidification and protein degradation in lysosomes, the fluorescence of R-PE remained intact over the whole observation period in the four cell lines. These results indicate that despite an efficient nanoparticle-mediated uptake of proteins by cells, a rapid endolysosomal degradation may prevent the desired (e.g. therapeutic effect of a protein inside a cell.

  19. 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...... and knowledge building as related to relational leading. The practices developed in the thesis research demonstrate that it is possible to create organizational learning and development through collaborative, dialogic practices in groups and teams, for instance combined with the use of roleplaying. In the work...... 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...

  20. Leading Hadron Production at HERA

    Directory of Open Access Journals (Sweden)

    Buniatyan Armen

    2013-06-01

    Full Text Available 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'γX as well as the leading neutron production in the photoproduction of dijets (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.

  1. [Noroviruses: leading cause of gastroenteritis].

    Science.gov (United States)

    Delacour, H; Dubrous, P; Koeck, J L

    2010-04-01

    Although noroviruses were the first viral agents to be linked to gastrointestinal disease, they were long considered a secondary cause far behind rotaviruses. Development of molecular-based diagnostic techniques has provided clearer insight into the epidemiological impact of noroviruses that are now recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks but also as an important cause of sporadic gastroenteritis in both children and adults. Norovirus infection is generally characterized by mild acute vomiting and diarrhea usually lasting for only a few days, but it can lead to more severe and potentially life-threatening symptoms in high-risk groups such as young children, elderly, and immunodeficient persons. It has been demonstrated that they are present in tropical countries. Molecular epidemiological studies have documented the great genetic diversity of noroviruses with regular emergence of variants. Since no vaccine is available, prevention on norovirus infection depends mainly on strict personal and community hygiene measures.

  2. Deformation properties of lead isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Tolokonnikov, S. V.; Borzov, I. N.; Lutostansky, Yu. S.; Saperstein, E. E., E-mail: saper43-7@mail.ru [National Research Center Kurchatov Institute (Russian Federation)

    2016-01-15

    The deformation properties of a long lead isotopic chain up to the neutron drip line are analyzed on the basis of the energy density functional (EDF) in the FaNDF{sup 0} Fayans form. The question of whether the ground state of neutron-deficient lead isotopes can have a stable deformation is studied in detail. The prediction of this deformation is contained in the results obtained on the basis of the HFB-17 and HFB-27 Skyrme EDF versions and reported on Internet. The present analysis reveals that this is at odds with experimental data on charge radii and magnetic moments of odd lead isotopes. The Fayans EDF version predicts a spherical ground state for all light lead isotopes, but some of them (for example, {sup 180}Pb and {sup 184}Pb) prove to be very soft—that is, close to the point of a phase transition to a deformed state. Also, the results obtained in our present study are compared with the predictions of some other Skyrme EDF versions, including SKM*, SLy4, SLy6, and UNE1. By and large, their predictions are closer to the results arising upon the application of the Fayans functional. For example, the SLy4 functional predicts, in just the same way as the FaNDF{sup 0} functional, a spherical shape for all nuclei of this region. The remaining three Skyrme EDF versions lead to a deformation of some light lead isotopes, but their number is substantially smaller than that in the case of the HFB-17 and HFB-27 functionals. Moreover, the respective deformation energy is substantially lower, which gives grounds to hope for the restoration of a spherical shape upon going beyond the mean-field approximation, which we use here. Also, the deformation properties of neutron-rich lead isotopes are studied up to the neutron drip line. Here, the results obtained with the FaNDF{sup 0} functional are compared with the predictions of the HFB-17, HFB-27, SKM*, and SLy4 Skyrme EDF versions. All of the EDF versions considered here predict the existence of a region where neutron

  3. String Formation Beyond Leading Colour

    CERN Document Server

    Christiansen, Jesper R.

    2015-08-03

    We present a new model for the hadronisation of multi-parton systems, in which colour correlations beyond leading $N_C$ 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 $e^+e^-$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 $1/N_C^2$ 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 $\\left(n_\\mathrm{charged})$ distribution but also with measured rates (and ra...

  4. 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

  5. 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

  6. Intercellular protein-protein interactions at synapses.

    Science.gov (United States)

    Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

    2014-06-01

    Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

  7. Non-interacting surface solvation and dynamics in protein-protein interactions

    NARCIS (Netherlands)

    Visscher, Koen M.; Kastritis, Panagiotis L.|info:eu-repo/dai/nl/315886668; Bonvin, Alexandre M J J|info:eu-repo/dai/nl/113691238

    2015-01-01

    Protein-protein interactions control a plethora of cellular processes, including cell proliferation, differentiation, apoptosis, and signal transduction. Understanding how and why proteins interact will inevitably lead to novel structure-based drug design methods, as well as design of de novo

  8. Tevatron HTS power lead test

    International Nuclear Information System (INIS)

    Feher, S.; Carcagno, R.; Orris, D.; Pischalnikov, Y.; Sylvester, C.; Tartaglia, M.; Tompkins, J.C.

    2004-01-01

    Two pairs of ASC 6 kA power leads developed for the Tevatron were successfully tested at Fermilab at over-current conditions. Stable operation was achieved while operating at a current of 9.56 kA for five hours and while continuously ramping between 0-9.56 kA at a ramp rate of 200 A/s for one hour. The minimum required liquid nitrogen flow rate was measured to be 1.5 g/s at 10 kA. After ramping up to 10 kA at 200A/s, it took only 15 minutes to stabilize the upper copper section of the lead with a flow of 1.8 g/s of liquid nitrogen vapor. Testing under extreme operating conditions--270-370 kPa liquid nitrogen vapor pressure and over 0.1 T external magnetic field--demonstrated that the HTS part of the lead can safely operate in the current sharing mode and that this design has large operating margin

  9. The LHC Lead Injector Chain

    CERN Document Server

    Beuret, A; Blas, A; Burkhardt, H; Carli, Christian; Chanel, M; Fowler, A; Gourber-Pace, M; Hancock, S; Hourican, M; Hill, C E; Jowett, John M; Kahle, K; Küchler, D; Lombardi, A M; Mahner, E; Manglunki, Django; Martini, M; Maury, S; Pedersen, F; Raich, U; Rossi, C; Royer, J P; Schindl, Karlheinz; Scrivens, R; Sermeus, L; Shaposhnikova, Elena; Tranquille, G; Vretenar, Maurizio; Zickler, T

    2004-01-01

    A sizeable part of the LHC physics programme foresees lead-lead collisions with a design luminosity of 1027 cm-2 s-1. This will be achieved after an upgrade of the ion injector chain comprising Linac3, LEIR, PS and SPS machines [1,2]. Each LHC ring will be filled in 10 min by almost 600 bunches, each of 7×107 lead ions. Central to the scheme is the Low Energy Ion Ring (LEIR) [3,4], which transforms long pulses from Linac3 into high-brilliance bunches by means of multi-turn injection, electron cooling and accumulation. Major limitations along the chain, including space charge, intrabeam scattering, vacuum issues and emittance preservation are highlighted. The conversion from LEAR (Low Energy Antiproton Ring) to LEIR involves new magnets and power converters, high-current electron cooling, broadband RF cavities, and a UHV vacuum system with getter (NEG) coatings to achieve a few 10-12 mbar. Major hardware changes in Linac3 and the PS are also covered. An early ion scheme with fewer bunches (but each at nominal...

  10. Natural convection in enclosures containing lead-bismuth and lead

    International Nuclear Information System (INIS)

    Dzodzo, M.; Cuckovic-Dzodzo, D.

    2001-01-01

    The design of liquid metal reactors such as Encapsulated Nuclear Heat Source (ENHS) which are based predominantly on the flow generated by natural convection effects demands knowledge of velocity and temperature fields, distribution of the local Nusselt numbers and values of the average Nusselt numbers for small coolant velocity regimes. Laminar natural convection in rectangular enclosures with different aspect ratios, containing lead-bismuth and lead is studied numerically in this paper. The numerical model takes into account variable properties of the liquid metals. The developed correlation for average Nusselt numbers is presented. It is concluded that average Nusselt numbers are lower than in 'normal' fluids (air, water and glycerol) for the same values of Rayleigh numbers. However, the heat flux, which can be achieved, is greater due to the high thermal conductivity of liquid metals. Some specific features of the flow fields generated by natural convection in liquid metals are presented. Their consequences on the design of heat exchangers for liquid metals are discussed. An application of the obtained results to the design of a new type of steam generator, which integrates the intermediate heat exchanger and secondary pool functions of the ENHS reactor, is presented. (authors)

  11. 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...

  12. Leading Baryon Production at HERA

    International Nuclear Information System (INIS)

    Dodonov, V.; Schmitt, S.

    2009-01-01

    The production of highly energetic forward neutrons has been studied in deep-inelastic scattering. The data were taken with the H1 detector at HERA in the years 2006-2007 and correspond to an integrated luminosity of 117 pb -1 . Semi-inclusive cross sections have been measured in the kinematic region 4 2 2 , 0.7*10 -4 -1 and the fractional momentum of the neutron 0.3 L T and compared to the predictions of models of leading neutron production. Differential cross sections for dijet photoproduction and in association with a leading neutron have been measured in the reaction e + p → e + jet jet X n with the ZEUS detector at HERA using an integrated luminosity of 40pb -1 . The data are consistent with a simple pion exchange model. The ratio of the neutron-tagged and dijet cross sections show violations of factorization of the lepton and photon vertices which can be explained by kinematic effects constraining the phase space for neutron production. Normalised double-differential leading-neutron cross sections have been measured in dijet photoproduction for the first time. The distributions can be fully characterised by only two energy dependent parameters extracted from fits to the data. Absorption effects were studied by comparing the dijet photoproduction measurements and similar results in deep inelastic scattering. No clear effect, not related to kinematics, was observed. In a resolved-enriched dijet photoproduction sample, significantly fewer neutrons were seen than for direct. This depletion can also be accounted for by kinematic constraints. The semi-inclusive reaction e + p → e + X p was studied with the ZEUS detector at HERA using an integrated luminosity of 12.8 pb -1 . The final state proton, which was detected with the ZEUS leading proton spectrometer, carried a large fraction of the incoming proton energy, x L > 0.32, and its transverse momentum squared satisfied p T 2 2 ; the exchanged photon virtuality, Q 2 , was greater than 3 GeV 2 and the range of

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Lead -- supply/demand outlook

    International Nuclear Information System (INIS)

    Schnull, T.

    1999-01-01

    As Japan goes--so goes the world. That was the title of a recent lead article in The Economist that soberly discussed the potential of much more severe global economic problems occurring, if rapid and coordinated efforts were not made to stabilize the economic situation in Asia in general, and in Japan in particular. During the first 6 months of last year, commodity markets reacted violently to the spreading economic problems in Asia. More recent currency and financial problems in Russia have exacerbated an already unpleasant situation. One commodity after another--including oil, many of the agricultural commodities, and each of the base metals--have dropped sharply in price. Many are now trading at multiyear lows. Until there is an overall improvement in the outlook for these regions, sentiment will likely continue to be negative, and metals prices will remain under pressure. That being said, lead has maintained its value better than many other commodities during these difficult times, finding support in relatively strong fundamentals. The author takes a closer look at those supply and demand fundamentals, beginning with consumption

  19. 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.-

  20. 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)

  1. Recycling abandoned lead battery sites

    International Nuclear Information System (INIS)

    Montgomery, A.H.

    1993-01-01

    In the past, automobile batteries were recycled principally for their lead content. The waste generated at battery wrecking facilities consisted of spent acid, crushed casings (ebonite and plastic), and where secondary smelting was involved, matte, slag, and carbon from the smelting process. These waste products were generally disposed in an on-site in a landfill or stored in piles. If the facility shut down because further commercial operations were not financially viable, the waste piles remained to be addressed at a later date through remedial action or reclamation programs. There are many of these facilities in the US. Nationally, about 28 sites have been discovered by the US Environmental Protection Agency (EPA) under the Superfund program and are under investigation or administrative orders for remedial action. A major remediation effort is now underway at the Gould Superfund Site in Portland, Oregon, which was operated as a secondary smelting facility between 1949 and 1981. This paper describes the nature of the contamination at the Gould site and the work conducted by Canonie Environmental Services Corp. (Canonie) to develop a process which would treat the waste from battery wrecking operations and produce revenue generating recyclable products while removing the source contamination (lead) from the site. The full-scale commercial plant is now operating and is expected to achieve a throughput rate of between 200 and 250 tons per day in the coming weeks

  2. Lead pollution, disease, and behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Bryce-Smith, D; Waldron, H A

    1974-01-01

    Sources and health effects of atmospheric lead pollution are reviewed. Most of the Pb in gasoline is emitted in the exhaust gases as an aerosol containing particles of inorganic Pb. Some organic Pb is present, but the amount is usually less than 10% of the total. The size of these particles (0.18 to 0.90 micron) ensures maximum pulmonary penetration and absorption. The fallout of airborne particles produces very high concentrations of Pb in city dust, both inside and outside houses. Unpolluted soil contains about 15 ppM Pb, but samples of city dust contain 1000 to 6000 ppM. A daily intake of as little as 30 mg of dust containing 3% Pb produces clinical Pb poisoning in a few months. There is clear evidence to support the thesis that current levels in the environment are capable of producing behavioral abnormalities of types associated with educational disorders and delinquency, and also evidence that delinquents tend to have abnormal lead metabolism.

  3. Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Praveen Kumar

    2014-01-01

    Full Text Available Withania somnifera (Ashwagandha, also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM resulted in normalization of glial fibrillary acidic protein (GFAP expression as well as heat shock protein (HSP70, mortalin, and neural cell adhesion molecule (NCAM expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx levels, catalase, and superoxide dismutase (SOD but not reduced glutathione (GSH contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

  4. What is lead-based paint?

    International Nuclear Information System (INIS)

    Vernon, L.S.

    1994-01-01

    The number of variety of lead-abatement regulations and requirements make it difficult and confusing to identify and properly respond to dangerous levels of lead in every situation. Definitions of ''lead-based paint'' and three test methods for lead detection are described to help determine when and how to test for the presence of lead

  5. Lead poisoning in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Scott, H M

    1963-08-17

    During the period 1957 to 1959 a considerable number of dogs were seen which were suffering from colic. Colic is not normally a condition commonly encountered in the dog, and the number of cases seen was large in proportion to the number of dogs in the population concerned. A number of other dogs exhibited nervous signs which varied from symptoms of mild anxiety to exaggerated fits. There was a certain amount of overlapping between the 2 groups in that some cases which originally only showed signs of colic later progressed to the stage where they showed nervous symptoms. The following report deals with 28 cases of lead poisoning in dogs and cats which occurred at Broken Hill, Northern Rhodesia. 8 references, 4 tables.

  6. 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

  7. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Esau, Luke E.

    2014-01-01

    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

  8. Is Your Child Safe from Lead Poisoning?

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Mary Jean Brown, chief of CDC's Lead Poisoning and Prevention Program, discusses the importance of testing children for lead poisoning, who should be tested, and what parents can do to prevent lead poisoning.

  9. Repeat Sequence Proteins as Matrices for Nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Drummy, L.; Koerner, H; Phillips, D; McAuliffe, J; Kumar, M; Farmer, B; Vaia, R; Naik, R

    2009-01-01

    Recombinant protein-inorganic nanocomposites comprised of exfoliated Na+ montmorillonite (MMT) in a recombinant protein matrix based on silk-like and elastin-like amino acid motifs (silk elastin-like protein (SELP)) were formed via a solution blending process. Charged residues along the protein backbone are shown to dominate long-range interactions, whereas the SELP repeat sequence leads to local protein/MMT compatibility. Up to a 50% increase in room temperature modulus and a comparable decrease in high temperature coefficient of thermal expansion occur for cast films containing 2-10 wt.% MMT.

  10. Heavy flavour production in proton-lead and lead-lead collisions with LHCb

    Science.gov (United States)

    Winn, Michael

    2017-11-01

    The LHCb experiment offers the unique opportunity to study heavy-ion interactions in the forward region (2 kinematic domain complementary to the other 3 large experiments at the LHC. The detector has excellent capabilities for reconstructing quarkonia and open charm states, including baryons, down to zero pT. It can separate the prompt and displaced charm components. In pPb collisions, both forward and backward rapidities are covered thanks to the possibility of beam reversal. Results include measurements of the nuclear modification factor and forward-backward ratio for charmonium, open charm and bottomonium states. These quantities are sensitive probes for nuclear effects in heavy flavour production. Perspectives are given with the large accumulated luminosity during the 2016 pPb run at the LHC. In 2015, LHCb participated successfully for the first time in the PbPb data-taking. The status of the forward prompt J/ψ nuclear modification factor measurement in lead-lead collisions is discussed.

  11. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  12. The identification of lead ammunition as a source of lead exposure in First Nations: The use of lead isotope ratios

    International Nuclear Information System (INIS)

    Tsuji, Leonard J.S.; Wainman, Bruce C.; Martin, Ian D.; Sutherland, Celine; Weber, Jean-Philippe; Dumas, Pierre; Nieboer, Evert

    2008-01-01

    The use of lead shotshell to hunt water birds has been associated with lead-contamination in game meat. However, evidence illustrating that lead shotshell is a source of lead exposure in subsistence hunting groups cannot be deemed definitive. This study seeks to determine whether lead shotshell constitutes a source of lead exposure using lead isotope ratios. We examined stable lead isotope ratios for lichens, lead shotshell and bullets, and blood from residents of Fort Albany and Kashechewan First Nations, and the City of Hamilton, Ontario, Canada. Data were analyzed using ANOVA and regression analyses. ANOVA of isotope ratios for blood revealed significant differences with respect to location, but not sex. Hamilton differed from both Kashechewan and Fort Albany; however, the First Nations did not differ from each other. ANOVA of the isotope ratios for lead ammunition and lichens revealed no significant differences between lichen groups (north and south) and for the lead ammunition sources (pellets and bullets). A plot of 206 Pb/ 204 Pb and 206 Pb/ 207 Pb values illustrated that lichens and lead ammunition were distinct groupings and only the 95% confidence ellipse of the First Nations group overlapped that of lead ammunition. In addition, partial correlations between blood-lead levels (adjusted for age) and isotope ratios revealed significant (p 206 Pb/ 204 Pb and 206 Pb/ 207 Pb, and a significant negative correlation for 208 Pb/ 206 Pb, as predicted if leaded ammunition were the source of lead exposure. In conclusion, lead ammunition was identified as a source of lead exposure for First Nations people; however, the isotope ratios for lead shotshell pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden

  13. Multiple protonation equilibria in electrostatics of protein-protein binding.

    Science.gov (United States)

    Piłat, Zofia; Antosiewicz, Jan M

    2008-11-27

    All proteins contain groups capable of exchanging protons with their environment. We present here an approach, based on a rigorous thermodynamic cycle and the partition functions for energy levels characterizing protonation states of the associating proteins and their complex, to compute the electrostatic pH-dependent contribution to the free energy of protein-protein binding. The computed electrostatic binding free energies include the pH of the solution as the variable of state, mutual "polarization" of associating proteins reflected as changes in the distribution of their protonation states upon binding and fluctuations between available protonation states. The only fixed property of both proteins is the conformation; the structure of the monomers is kept in the same conformation as they have in the complex structure. As a reference, we use the electrostatic binding free energies obtained from the traditional Poisson-Boltzmann model, computed for a single macromolecular conformation fixed in a given protonation state, appropriate for given solution conditions. The new approach was tested for 12 protein-protein complexes. It is shown that explicit inclusion of protonation degrees of freedom might lead to a substantially different estimation of the electrostatic contribution to the binding free energy than that based on the traditional Poisson-Boltzmann model. This has important implications for the balancing of different contributions to the energetics of protein-protein binding and other related problems, for example, the choice of protein models for Brownian dynamics simulations of their association. Our procedure can be generalized to include conformational degrees of freedom by combining it with molecular dynamics simulations at constant pH. Unfortunately, in practice, a prohibitive factor is an enormous requirement for computer time and power. However, there may be some hope for solving this problem by combining existing constant pH molecular dynamics

  14. Protein-Protein Interaction Databases

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Jensen, Lars Juhl

    2015-01-01

    Years of meticulous curation of scientific literature and increasingly reliable computational predictions have resulted in creation of vast databases of protein interaction data. Over the years, these repositories have become a basic framework in which experiments are analyzed and new directions...

  15. Shorts due to diagnostic leads

    International Nuclear Information System (INIS)

    Ellis, J.F.; Lubell, M.S.; Pillsbury, R.D.; Shen, S.S.; Thome, R.J.; Walstrom, P.L.

    1985-01-01

    The superconducting toroidal field coils that are being tested in the Large Coil Test Facility (LCTF) are heavily instrumented. General Electric coil, a lead wire of an internal sensor became shorted across an estimated three or four turns of the pancake winding. This short occurred during the final stages of the winding fabrication and was not accessible for repair. Resistance, voltage gradient, and transient voltage decay measurements were performed to characterize the short and the magnetic damping of the large steel bobbin and outer structural ring. The 32-gage wire causing the short was estimated to be about 10 cm long, with a resistance of 55 mΩ. As a safety measure, we decided to burn out the shorted wire at room temperature before installing the coil in LCTF. Tests were made to determine the energy needed to vaporize a small wire. Computer calculations indicated that within the voltage limits set for the coil, it was not feasible to burn out the wire by rapidly dumping the coil from a low-current dc charge-up. We accomplished the burnout by applying 800 V at 3.25 A, and 60 Hz for about 1 s. Transient voltage decay measurements made after the burnout and compared with those made before the attempt confirmed that the short had indeed been opened

  16. Leading local politicians visit CERN

    CERN Multimedia

    2001-01-01

    Left to right:  Professor Maiani, Ernest Nycollin, Anne-Marie Comparini, and Jean Pépin surrounded by young PRAC. On the 13th of November leading local politicians : Mme Anne-Marie Comparini, Présidente du Conseil régional de Rhône-Alpes, M. Ernest Nycollin, Président du Conseil général de la Haute-Savoie et M. Jean Pépin, Président du Conseil général de l'Ain took part in a ceremony which featured the insertion of one of the first LHC magnets into its cryostat.  The department of l'Ain financed a large part of the contruction of building SMA 18 which will see intense activity during the assembly of LHC magnets over the next four years. The department of Haute-Savoie helped in the development of the ultrasonic welding machine for the superconducting cables and the conception of integrated circuits that will be used to measure temperature and pressure inside the magnets. T...

  17. Heme synthesis in the lead-intoxicated mouse embryo

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, G B; Maes, J

    1978-02-01

    Incorporation of /sup 55/Fe and of (/sup 14/C) glycine was studied in control embryos and mothers and in those which had received lead in the diet from day 7 of pregnancy. Incorporation of Fe into heme of embryonic liver which increases markedly for controls on day 17 of pregnancy was depressed greatly and showed no such increase in lead-intoxicated embryos. These embryos were retarded in growth but had normal heme concentrations in body and liver. Incorporation of glycine into embryonic heme and proteins was not affected. Data on incorporation in the mothers are also presented. It is thought that the impaired synthesis of heme in lead-intoxicated embryos limits their body growth during the late phase of pregnancy.

  18. Results from the Cooler and Lead Tests

    International Nuclear Information System (INIS)

    Green, Michael A.

    2010-01-01

    The report presents the results of testing MICE spectrometer magnet current leads on a test apparatus that combines both the copper leads and the high temperature superconducting (HTS) leads with a single Cryomech PT415 cooler and liquid helium tank. The current is carried through the copper leads from 300 K to the top of the HTS leads. The current is then carried through the HTS leads to a feed-through from the vacuum space to the inside of a liquid helium tank. The experiment allows one to measure the performance of both cooler stages along with the performance of the leads. While the leads were powered we measured the voltage drops through the copper leads, through the HTS leads, through spliced to the feed-through, through the feed-through and through the low-temperature superconducting loop that connects one lead to the other. Measurements were made using the leads that were used in spectrometer magnet 1A and spectrometer magnet 2A. These are the same leads that were used for Superbend and Venus magnets at LBNL. The IL/A for these leads was 5.2 x 10 6 m -1 . The leads turned out to be too long. The same measurements were made using the leads that were installed in magnet 2B. The magnet 2B leads had an IL/A of 3.3 x 10 6 A m -1 . This report discusses the cooler performance and the measured electrical performance of the lead circuit that contains the copper leads and the superconducting leads. All of the HTS leads that were installed in magnet 2B were current tested using this apparatus.

  19. Current strategies for protein production and purification enabling membrane protein structural biology.

    Science.gov (United States)

    Pandey, Aditya; Shin, Kyungsoo; Patterson, Robin E; Liu, Xiang-Qin; Rainey, Jan K

    2016-12-01

    Membrane proteins are still heavily under-represented in the protein data bank (PDB), owing to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles, owing to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and (or) amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through the introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).

  20. Dietary exposure to lead in the Netherlands

    NARCIS (Netherlands)

    Boon PE; te Biesebeek JD; van Donkersgoed G; VVH; V&Z

    2017-01-01

    Uptake from the soil is the main route by which lead ends up in food. Lead in soil has its origin in both natural and anthropogenic sources. The lead concentration in food has decreased over the last decennia by the use of unleaded petrol and paint, and the replacement of lead water pipes.

  1. Women researchers lead wage hikes

    Science.gov (United States)

    Bell, Peter M.

    Women employed in the research and development fields in universities, government, and industry made substantial increases and lead men in salary gains in 1981, according to a far-reaching survey of 5000 respondents (Industrial Research and Development, April 1982). At the upper end, 20% of women researchers received salary increases of 14% or more, compared to 13% of the men. The raises were high in 1981; more than half the women in research and development had salary gains of over 9%.The employment picture for women in the scientific and technical fields is somewhat complicated by the affirmative efforts of hiring. More women were hired in 1981, and most newly hired women and men begin at the lowest salaries. This factor contributed to the reality that more women than men at the lower salary ranges received zero raises. However, according to the survey, this is not a trend, since the current efforts to add women in research fields are providing more rewards for women per amount of experience than for men: “…women working in R&D have far less experience than their male counterparts.” (IR&D, op cit.). The median years of experience is down in 1981 from previous years. Some 40% of the women surveyed had less than 6 years experience, compared to about 14% of the men. These figures contrast with those of the survey trends of previous years, which indicated a direct relation between salary and experience. It is still true that because larger numbers of men have over 16 years of experience, the highest paid employees in research and development fields are men. It is noted, however, that in the beginning salary scales ($16-27 k/yr) women outnumber men.

  2. Lead isotope analyses of standard rock samples

    International Nuclear Information System (INIS)

    Koide, Yoshiyuki; Nakamura, Eizo

    1990-01-01

    New results on lead isotope compositions of standard rock samples and their analytical procedures are reported. Bromide form anion exchange chromatography technique was adopted for the chemical separation lead from rock samples. The lead contamination during whole analytical procedure was low enough to determine lead isotope composition of common natural rocks. Silica-gel activator method was applied for emission of lead ions in the mass spectrometer. Using the data reduction of 'unfractionated ratios', we obtained good reproducibility, precision and accuracy on lead isotope compositions of NBS SRM. Here we present new reliable lead isotope compositions of GSJ standard rock samples and USGS standard rock, BCR-1. (author)

  3. Measurement of lead compound in stack gas

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Y; Hori, M; Tanikawa, N

    1979-01-01

    The concentration and particle-size distribution of lead compounds in the exhaust gas from various stationary sources are examined. The stationary sources concern lead production from battery scraps, lead smelting of cable mold, steel production from iron scraps, plastic combustion furnace, and a heavy oil boiler. A lead concentration of 0.2-100 mg/cu m in exhaust gas is detected. Furthermore, exhaust gas lead compounds are affected by the raw materials used.

  4. PSAIA – Protein Structure and Interaction Analyzer

    Directory of Open Access Journals (Sweden)

    Vlahoviček Kristian

    2008-04-01

    Full Text Available Abstract Background PSAIA (Protein Structure and Interaction Analyzer was developed to compute geometric parameters for large sets of protein structures in order to predict and investigate protein-protein interaction sites. Results In addition to most relevant established algorithms, PSAIA offers a new method PIADA (Protein Interaction Atom Distance Algorithm for the determination of residue interaction pairs. We found that PIADA produced more satisfactory results than comparable algorithms implemented in PSAIA. Particular advantages of PSAIA include its capacity to combine different methods to detect the locations and types of interactions between residues and its ability, without any further automation steps, to handle large numbers of protein structures and complexes. Generally, the integration of a variety of methods enables PSAIA to offer easier automation of analysis and greater reliability of results. PSAIA can be used either via a graphical user interface or from the command-line. Results are generated in either tabular or XML format. Conclusion In a straightforward fashion and for large sets of protein structures, PSAIA enables the calculation of protein geometric parameters and the determination of location and type for protein-protein interaction sites. XML formatted output enables easy conversion of results to various formats suitable for statistic analysis. Results from smaller data sets demonstrated the influence of geometry on protein interaction sites. Comprehensive analysis of properties of large data sets lead to new information useful in the prediction of protein-protein interaction sites.

  5. The effect of lead poisoning on hematologic and biochemical values in trumpeter swans and Canada geese.

    Science.gov (United States)

    Katavolos, P; Staempfli, S; Sears, W; Gancz, A Y; Smith, D A; Bienzle, D

    2007-12-01

    Lead is a persistent contaminant in the environment, and waterfowl are susceptible to lead toxicity from ingestion of lead pellets and fishing weights. Lead affects numerous physiologic processes through inhibition of enzyme activity and protein function, but its effects on commonly assessed avian blood values are incompletely understood. Our aim was to evaluate hematologic and biochemical changes associated with blood lead concentrations in trumpeter swans and Canada geese. Data for CBCs, plasma biochemical profiles (total protein, albumin, glucose, cholesterol, total bilirubin, calcium, phosphorus, gamma-glutamyltransferase [GGT], aspartate aminotransferase, lactate dehydrogenase, glutamate dehydrogenase, creatine kinase, amylase, and lipase), and whole blood lead concentrations were retrospectively analyzed for 69 trumpeter swans and 52 Canada geese. Laboratory data obtained prospectively from an additional 20 trumpeter swans also were included. RBC morphology was semiquantitated in blood smears from 70 of the birds. Data were analyzed initially by ANOVA and covariance. A statistical model then was constructed to determine the relationship between each parameter and lead concentration. In both avian species, PCV, hemoglobin concentration, and MCHC decreased significantly (P < .05) with increasing blood lead concentration. Uric acid concentration and GGT activity were increased in trumpeter swans and phosphorus concentration was decreased in Canada geese in association with high blood lead concentration (P < .05). Lead toxicosis induced significant changes in the values of commonly measured hematologic parameters in waterfowl. These changes may be useful indicators of severe lead intoxication during routine laboratory assessment. Changes in clinical chemistry values, although statistically significant, were too inconsistent to serve as indicators of lead toxicosis.

  6. Aquaporin Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer Virginia Roche

    2017-10-01

    Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

  7. Hematological alterations in protein malnutrition.

    Science.gov (United States)

    Santos, Ed W; Oliveira, Dalila C; Silva, Graziela B; Tsujita, Maristela; Beltran, Jackeline O; Hastreiter, Araceli; Fock, Ricardo A; Borelli, Primavera

    2017-11-01

    Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Effect of lead nitrate on thyroid function on the Indian palm squirrel, Funambulus pennanti (Wroughton)

    International Nuclear Information System (INIS)

    Shrivastava, V.K.; Katti, S.R.; Sathyanesan, A.G.

    1987-01-01

    Some of the known toxic effects of lead in mammals including man are, impaired heme synthesis, anemia, nepatopathy, nephropathy, behavioral disorders and neuropathy. However, very little is known about the effect of lead on endocrine physiology. Some data are available on lead induced impairment of thyroid function in occupationally exposed men and experimental rats. As lead nitrate is largely consumed through water and food, in this study the wild rodents Funambulus pennanti were administered lead through their drinking water and their thyroid structure, radioiodine 131-I percentage uptake and protein bound iodine (PBI) level were assessed

  9. Protein immobilization strategies for protein biochips

    NARCIS (Netherlands)

    Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

    2007-01-01

    In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

  10. Protein engineering and its applications in food industry.

    Science.gov (United States)

    Kapoor, Swati; Rafiq, Aasima; Sharma, Savita

    2017-07-24

    Protein engineering is a young discipline that has been branched out from the field of genetic engineering. Protein engineering is based on the available knowledge about the proteins structure/function(s), tools/instruments, software, bioinformatics database, available cloned gene, knowledge about available protein, vectors, recombinant strains and other materials that could lead to change in the protein backbone. Protein produced properly from genetic engineering process means a protein that is able to fold correctly and to do particular function(s) efficiently even after being subjected to engineering practices. Protein is modified through its gene or chemically. However, modification of protein through gene is easier. There is no specific limitation of Protein Engineering tools; any technique that can lead to change the protein constituent of amino acid and result in the modification of protein structure/function is in the frame of Protein Engineering. Meanwhile, there are some common tools used to reach a specific target. More active industrial and pharmaceutical based proteins have been invented by the field of Protein Engineering to introduce new function as well as to change its interaction with surrounding environment. A variety of protein engineering applications have been reported in the literature. These applications range from biocatalysis for food and industry to environmental, medical and nanobiotechnology applications. Successful combinations of various protein engineering methods had led to successful results in food industries and have created a scope to maintain the quality of finished product after processing.

  11. Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment.

    Science.gov (United States)

    Hernández-Plata, Everardo; Quiroz-Compeán, Fátima; Ramírez-Garcia, Gonzalo; Barrientos, Eunice Yáñez; Rodríguez-Morales, Nadia M; Flores, Alberto; Wrobel, Katarzina; Wrobel, Kazimierz; Méndez, Isabel; Díaz-Muñoz, Mauricio; Robles, Juvencio; Martínez-Alfaro, Minerva

    2015-03-04

    Melatonin, a hormone known for its effects on free radical scavenging and antioxidant activity, can reduce lead toxicity in vivo and in vitro.We examined the effects of melatonin on lead bio-distribution. Rats were intraperitoneally injected with lead acetate (10, 15 or 20mg/kg/day) with or without melatonin (10mg/kg/day) daily for 10 days. In rats intoxicated with the highest lead doses, those treated with melatonin had lower lead levels in blood and higher levels in urine and feces than those treated with lead alone, suggesting that melatonin increases lead excretion. To explore the mechanism underlying this effect, we first assessed whether lead/melatonin complexes were formed directly. Electronic density functional (DFT) calculations showed that a lead/melatonin complex is energetically feasible; however, UV spectroscopy and NMR analysis showed no evidence of such complexes. Next, we examined the liver mRNA levels of metallothioneins (MT) 1 and 2. Melatonin cotreatment increased the MT2 mRNA expression in the liver of rats that received the highest doses of lead. The potential effects of MTs on the tissue distribution and excretion of lead are not well understood. This is the first report to suggest that melatonin directly affects lead levels in organisms exposed to subacute lead intoxication. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. The effect of lead intoxication on endocrine functions.

    Science.gov (United States)

    Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

    2009-02-01

    Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

  13. Acute and chronic lead poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    Iosif, C

    1966-02-01

    Three cases of acute plumbism in cows are detailed: one of a six-year-old cow who accidentally ate about 100 gm. of lead (in 1956); the second of a 12-year-old cow who accidentally ate a packet containing about 100 gm. of lead used in painting; and the third of a three-week-old heifer who licked a freshly painted bucket. Route of exposure to lead can be gastrointestinal following deposition of lead fumes (lead oxide, sulfide, and sulfate) on pasturage and in exposed drinking water, or respiratory following the inhalation of such fumes. The presence of CO/sub 2/ in the respiratory tract is thought to provide a favorable situation for the dissolution of lead and the formation of soluble lead complexes. One author has calculated that 12% of respired lead is absorbed into the organism, while only 1-2% of ingested lead is absorbed.

  14. Neurobehavioural effects of occupational exposure to lead.

    Science.gov (United States)

    Williamson, A M; Teo, R K

    1986-06-01

    A set of neurobehavioural tests selected on the basis of information processing theory was used to study the effect of low level occupational lead exposure on 59 lead workers compared with a matched control group of the same number. Only one of the lead exposed group had a blood lead concentration above the current threshold limit value of 3.81 mumol/l at the time of testing (mean 2.36 mumol/l, range 1.19-3.92 mumol/l) and none had been detected above that level in the previous three years. Nevertheless, most neurobehavioural functions tested showed some impairment in the lead workers. Visual sensory function was affected and, perhaps as a consequence, sustained attention and psychomotor tasks were performed more slowly by the lead exposed group. Cognitive functions were also impaired, with sensory store memory, short term memory, and learning abilities all showing deficits in lead workers. Such cognitive deficits may also be partly due to initial degradation of the visual input. Long term memory performance compared equally with control levels possibly because of development of a compensatory strategy such as rehearsal by the lead exposed subjects. Multiple linear regression analysis relating to lead workers test performance and their lead exposure showed that performance on the sensory store memory test alone was significantly related to exposure. This was probably due to the homogeneity of the lead exposed group with regard to blood lead concentrations and the use of blood lead as a measure of chronic lead exposure.

  15. Neurobehavioural effects of occupational exposure to lead

    Energy Technology Data Exchange (ETDEWEB)

    Williamson, A.M.; Teo, R.K.

    1986-06-01

    A set of neurobehavioural tests selected on the basis of information processing theory was used to study the effect of low level occupational lead exposure on 59 lead workers compared with a matched control group of the same number. Only one of the lead exposed group had a blood lead concentration above the current threshold limit value of 3.81 mumol/l at the time of testing (mean 2.36 mumol/l, range 1.19-3.92 mumol/l) and none had been detected above that level in the previous three years. Nevertheless, most neurobehavioural functions tested showed some impairment in the lead workers. Visual sensory function was affected and, perhaps as a consequence, sustained attention and psychomotor tasks were performed more slowly by the lead exposed group. Cognitive functions were also impaired, with sensory store memory, short term memory, and learning abilities all showing deficits in lead workers. Such cognitive deficits may also be partly due to initial degradation of the visual input. Long term memory performance compared equally with control levels possibly because of development of a compensatory strategy such as rehearsal by the lead exposed subjects. Multiple linear regression analysis relating to lead workers test performance and their lead exposure showed that performance on the sensory store memory test alone was significantly related to exposure. This was probably due to the homogeneity of the lead exposed group with regard to blood lead concentrations and the use of blood lead as a measure of chronic lead exposure.

  16. Kinetics of oil saponification by lead salts in ancient preparations of pharmaceutical lead plasters and painting lead mediums.

    Science.gov (United States)

    Cotte, M; Checroun, E; Susini, J; Dumas, P; Tchoreloff, P; Besnard, M; Walter, Ph

    2006-12-15

    Lead soaps can be found in archaeological cosmetics as well as in oil paintings, as product of interactions of lead salts with oil. In this context, a better understanding of the formation of lead soaps allows a follow-up of the historical evolution of preparation recipes and provides new insights into conservation conditions. First, ancient recipes of both pharmaceutical lead plasters and painting lead mediums, mixtures of oil and lead salts, were reconstructed. The ester saponification by lead salts is determined by the preparation parameters which were quantified by FT-IR spectrometry. In particular, ATR/FT-IR spectrometer was calibrated by the standard addition method to quantitatively follow the kinetics of this reaction. The influence of different parameters such as temperature, presence of water and choice of lead salts was assessed: the saponification is clearly accelerated by water and heating. This analysis provides chemical explanations to the historical evolution of cosmetic and painting preparation recipes.

  17. Frustration in Condensed Matter and Protein Folding

    Science.gov (United States)

    Li, Z.; Tanner, S.; Conroy, B.; Owens, F.; Tran, M. M.; Boekema, C.

    2014-03-01

    By means of computer modeling, we are studying frustration in condensed matter and protein folding, including the influence of temperature and Thomson-figure formation. Frustration is due to competing interactions in a disordered state. The key issue is how the particles interact to reach the lowest frustration. The relaxation for frustration is mostly a power function (randomly assigned pattern) or an exponential function (regular patterns like Thomson figures). For the atomic Thomson model, frustration is predicted to decrease with the formation of Thomson figures at zero kelvin. We attempt to apply our frustration modeling to protein folding and dynamics. We investigate the homogeneous protein frustration that would cause the speed of the protein folding to increase. Increase of protein frustration (where frustration and hydrophobicity interplay with protein folding) may lead to a protein mutation. Research is supported by WiSE@SJSU and AFC San Jose.

  18. Leading gravitational corrections and a unified universe

    DEFF Research Database (Denmark)

    Codello, Alessandro; Jain, Rajeev Kumar

    2016-01-01

    Leading order gravitational corrections to the Einstein-Hilbert action can lead to a consistent picture of the universe by unifying the epochs of inflation and dark energy in a single framework. While the leading local correction induces an inflationary phase in the early universe, the leading...... nonlocal term leads to an accelerated expansion of the universe at the present epoch. We argue that both the leading UV and IR terms can be obtained within the framework of a covariant effective field theory of gravity. The perturbative gravitational corrections therefore provide a fundamental basis...

  19. Exciton-relaxation dynamics in lead halides

    International Nuclear Information System (INIS)

    Iwanaga, Masanobu; Hayashi, Tetsusuke

    2003-01-01

    We survey recent comprehensive studies of exciton relaxation in the crystals of lead halides. The luminescence and electron-spin-resonance studies have revealed that excitons in lead bromide spontaneously dissociate and both electrons and holes get self-trapped individually. Similar relaxation has been also clarified in lead chloride. The electron-hole separation is ascribed to repulsive correlation via acoustic phonons. Besides, on the basis of the temperature profiles of self-trapped states, we discuss the origin of luminescence components which are mainly induced under one-photon excitation into the exciton band in lead fluoride, lead chloride, and lead bromide

  20. Prion Protein and Aging

    Directory of Open Access Journals (Sweden)

    Lisa eGasperini

    2014-08-01

    Full Text Available The cellular prion protein (PrPC has been widely investigated ever since its conformational isoform, the prion (or PrPSc, was identified as the etiological agent of prion disorders. The high homology shared by the PrPC-encoding gene among mammals, its high turnover rate and expression in every tissue strongly suggest that PrPC may possess key physiological functions. Therefore, defining PrPC roles, properties and fate in the physiology of mammalian cells would be fundamental to understand its pathological involvement in prion diseases. Since the incidence of these neurodegenerative disorders is enhanced in aging, understanding PrPC functions in this life phase may be of crucial importance. Indeed, a large body of evidence suggests that PrPC plays a neuroprotective and antioxidant role. Moreover, it has been suggested that PrPC is involved in Alzheimer disease, another neurodegenerative pathology that develops predominantly in the aging population. In prion diseases, PrPC function is likely lost upon protein aggregation occurring in the course of the disease. Additionally, the aging process may alter PrPC biochemical properties, thus influencing its propensity to convert into PrPSc. Both phenomena may contribute to the disease development and progression. In Alzheimer disease, PrPC has a controversial role because its presence seems to mediate β-amyloid toxicity, while its down-regulation correlates with neuronal death. The role of PrPC in aging has been investigated from different perspectives, often leading to contrasting results. The putative protein functions in aging have been studied in relation to memory, behavior and myelin maintenance. In aging mice, PrPC changes in subcellular localization and post-translational modifications have been explored in an attempt to relate them to different protein roles and propensity to convert into PrPSc. Here we provide an overview of the most relevant studies attempting to delineate PrPC functions and

  1. Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand*

    Science.gov (United States)

    Teasley, Daniel C.; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R.; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A.

    2015-01-01

    The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. PMID:25922071

  2. Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand.

    Science.gov (United States)

    Teasley, Daniel C; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A

    2015-06-12

    The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Ten Leading Causes of Death and Injury

    Science.gov (United States)

    ... Overdose Traumatic Brain Injury Violence Prevention Ten Leading Causes of Death and Injury Recommend on Facebook Tweet Share Compartir ... in Hospital Emergency Departments, United States – 2014 Leading Causes of Death Charts Causes of Death by Age Group 2016 [ ...

  4. A Public Health Approach to Addressing Lead

    Science.gov (United States)

    Describes EPA’s achievements in reducing childhood lead exposures and emphasizes the need to continue actions to further reduce lead exposures, especially in those communities where exposures remain high.

  5. Lead Intoxication in Children in Birmingham

    Science.gov (United States)

    Betts, P. R.; Astley, R.; Raine, D. N.

    1973-01-01

    Of 38 children investigated between 1966 and 1971 who had a blood lead concentration greater than 37 μg/100 ml eight had encephalopathy and one died; all these eight had a blood lead concentration of 99 μg/100 ml or above. Blood lead levels are related to haemoglobin concentrations and anaemia is common in children with blood lead concentrations of 37-60 μg/100 ml, levels previously accepted as harmless. Children with blood lead concentrations greater than 60 μg/100 ml show radiological evidence of lead intoxication, and treatment for this should be considered when blood lead concentration exceeds 37 μg/100 ml. Children presenting with unexplained encephalopathy should be radiographed for evidence of lead intoxication. ImagesFIG. 2FIG. 1 PMID:4691065

  6. Lead's Impact on Indoor Air Quality

    Science.gov (United States)

    Lead has long been recognized as a harmful environmental pollutant. There are many ways in which humans are exposed to lead: through air, drinking water, food, contaminated soil, deteriorating paint, and dust.

  7. Leading particle in deep inelastic scattering

    International Nuclear Information System (INIS)

    Petrov, V.A.

    1984-01-01

    The leading particle effect in deep inelastic scattering is considered. The change of the characteris cs shape of the leading particle inclusive spectrum with Q 2 is estimated to be rather significant at very high Q 2

  8. Selection of peptides interfering with protein-protein interaction.

    Science.gov (United States)

    Gaida, Annette; Hagemann, Urs B; Mattay, Dinah; Räuber, Christina; Müller, Kristian M; Arndt, Katja M

    2009-01-01

    Cell physiology depends on a fine-tuned network of protein-protein interactions, and misguided interactions are often associated with various diseases. Consequently, peptides, which are able to specifically interfere with such adventitious interactions, are of high interest for analytical as well as medical purposes. One of the most abundant protein interaction domains is the coiled-coil motif, and thus provides a premier target. Coiled coils, which consist of two or more alpha-helices wrapped around each other, have one of the simplest interaction interfaces, yet they are able to confer highly specific homo- and heterotypic interactions involved in virtually any cellular process. While there are several ways to generate interfering peptides, the combination of library design with a powerful selection system seems to be one of the most effective and promising approaches. This chapter guides through all steps of such a process, starting with library options and cloning, detailing suitable selection techniques and ending with purification for further down-stream characterization. Such generated peptides will function as versatile tools to interfere with the natural function of their targets thereby illuminating their down-stream signaling and, in general, promoting understanding of factors leading to specificity and stability in protein-protein interactions. Furthermore, peptides interfering with medically relevant proteins might become important diagnostics and therapeutics.

  9. Lead contamination of inexpensive plastic jewelry

    Energy Technology Data Exchange (ETDEWEB)

    Yost, Jamie L. [Department of Chemistry, Ashland University, Ashland, Ohio (United States); Weidenhamer, Jeffrey D. [Department of Chemistry, Ashland University, Ashland, Ohio (United States)], E-mail: jweiden@ashland.edu

    2008-04-15

    The neurological hazards of lead to children are well-known. As a result of recent documented cases of lead poisoning, regulatory attention in the United States has focused on the lead content of children's metal jewelry. By contrast, little is known about the possible hazards of plastic jewelry items. The objective of this study was to determine whether inexpensive plastic jewelry is a possible source of toxic lead for children. Samples of more than 100 inexpensive plastic jewelry items were analyzed for lead content. Beads were screened by soaking in 1 M nitric acid. Nine items found to release more than 30 {mu}g of lead per bead were further tested for accessible lead, and scrapings of the bead coatings were analyzed for total lead content. The maximum accessible lead found was 49 {mu}g per bead, which is below the current US Consumer Product Safety Commission limit of 175 {mu}g. However, when the number of beads in each item was taken into account, six of the nine leaded samples contained more than 175 {mu}g accessible lead per item. The lead in these items appears to be associated with lead-based paints used to produce glossy coatings on imitation pearls and similar items. Coatings obtained by scraping individual beads contained 3.5-23% lead, which far exceeds the US regulatory limit of 0.06% lead in paints on items intended for children. Our results demonstrate that plastic jewelry items merit the attention of public health and consumer protection agencies seeking to limit the exposure of children to lead.

  10. 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.

  11. 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.

  12. Lead contamination of inexpensive plastic jewelry

    International Nuclear Information System (INIS)

    Yost, Jamie L.; Weidenhamer, Jeffrey D.

    2008-01-01

    The neurological hazards of lead to children are well-known. As a result of recent documented cases of lead poisoning, regulatory attention in the United States has focused on the lead content of children's metal jewelry. By contrast, little is known about the possible hazards of plastic jewelry items. The objective of this study was to determine whether inexpensive plastic jewelry is a possible source of toxic lead for children. Samples of more than 100 inexpensive plastic jewelry items were analyzed for lead content. Beads were screened by soaking in 1 M nitric acid. Nine items found to release more than 30 μg of lead per bead were further tested for accessible lead, and scrapings of the bead coatings were analyzed for total lead content. The maximum accessible lead found was 49 μg per bead, which is below the current US Consumer Product Safety Commission limit of 175 μg. However, when the number of beads in each item was taken into account, six of the nine leaded samples contained more than 175 μg accessible lead per item. The lead in these items appears to be associated with lead-based paints used to produce glossy coatings on imitation pearls and similar items. Coatings obtained by scraping individual beads contained 3.5-23% lead, which far exceeds the US regulatory limit of 0.06% lead in paints on items intended for children. Our results demonstrate that plastic jewelry items merit the attention of public health and consumer protection agencies seeking to limit the exposure of children to lead

  13. Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

    OpenAIRE

    Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-01-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

  14. 40 CFR 1508.16 - Lead agency.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Lead agency. 1508.16 Section 1508.16 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY TERMINOLOGY AND INDEX § 1508.16 Lead agency. Lead agency means the agency or agencies preparing or having taken primary responsibility for preparing the...

  15. Is Your Child Safe from Lead Poisoning?

    Centers for Disease Control (CDC) Podcasts

    2008-10-02

    In this podcast, Dr. Mary Jean Brown, chief of CDC's Lead Poisoning and Prevention Program, discusses the importance of testing children for lead poisoning, who should be tested, and what parents can do to prevent lead poisoning.  Created: 10/2/2008 by National Center for Environmental Health (NCEH).   Date Released: 10/2/2008.

  16. Significance of Lead Residues in Mallard Tissues

    Science.gov (United States)

    Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

    1974-01-01

    Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

  17. Early Reading Proficiency. Leading Indicator Spotlight

    Science.gov (United States)

    Musen, Lindsey

    2010-01-01

    In "Beyond Test Scores: Leading Indicators for Education," Foley and colleagues (2008) define leading indicators as those that "provide early signals of progress toward academic achievement" (p. 1) and stress that educators "need leading indicators to help them see the direction their efforts are going in and to take…

  18. Radioactive lead studies in the human

    International Nuclear Information System (INIS)

    Blake, K.C.H.

    1980-08-01

    The differing susceptibility of individuals to the toxic effects of chronic lead exposure has never been fully understood. As the major intake of lead in the human is from food and beverages, any variation between individuals of the quantity of lead absorbed from the gut, and of the distribution and excretion of this lead, may account for the differences in individual susceptibility. The food and beverages themselves may have an influence, and to investigate their effects on absorption, distribution and excretion of lead, experiments were performed on normal subjects using a short lived radionuclide of lead, 203 Pb, and instruments generally available in Nuclear Medicine. Lead absorption between different individuals showed a wide variation when 203 Pb was taken as a single dose between meals. Minerals were found to be mainly responsible for affecting absorption when one subject ingested 203 Pb in control meals from which one dietary constituent at a time was omitted. Calcium and phosphorous were found to reduce the absorption of 203 Pb to approximately the same level as that produced by the total minerals. Calcium reduced absorption more than phosphorous when these minerals were ingested separately with 203 Pb. It was concluded that the calcium and phosphorous in the diet could influence susceptibility to lead toxicity through changes in the absorption of food and water lead and in the distribution of lead in the body. The results suggest that the prophylactic effect of calcium on lead absorption should be recognised and applied in this time of increased environmental levels of lead

  19. Eryptosis in lead-exposed workers

    International Nuclear Information System (INIS)

    Aguilar-Dorado, Itzel-Citlalli; Hernández, Gerardo; Quintanar-Escorza, Martha-Angelica; Maldonado-Vega, María; Rosas-Flores, Margarita; Calderón-Salinas, José-Víctor

    2014-01-01

    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 2+ ] 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 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 showed higher PS

  20. 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

  1. A green lead hydrometallurgical process based on a hydrogen-lead oxide fuel cell.

    Science.gov (United States)

    Pan, Junqing; Sun, Yanzhi; Li, Wei; Knight, James; Manthiram, Arumugam

    2013-01-01

    The automobile industry consumed 9 million metric tons of lead in 2012 for lead-acid batteries. Recycling lead from spent lead-acid batteries is not only related to the sustainable development of the lead industry, but also to the reduction of lead pollution in the environment. The existing lead pyrometallurgical processes have two main issues, toxic lead emission into the environment and high energy consumption; the developing hydrometallurgical processes have the disadvantages of high electricity consumption, use of toxic chemicals and severe corrosion of metallic components. Here we demonstrate a new green hydrometallurgical process to recover lead based on a hydrogen-lead oxide fuel cell. High-purity lead, along with electricity, is produced with only water as the by-product. It has a >99.5% lead yield, which is higher than that of the existing pyrometallurgical processes (95-97%). This greatly reduces lead pollution to the environment.

  2. Protein interfacial structure and nanotoxicology

    International Nuclear Information System (INIS)

    White, John W.; Perriman, Adam W.; McGillivray, Duncan J.; Lin, J.-M.

    2009-01-01

    Here we briefly recapitulate the use of X-ray and neutron reflectometry at the air-water interface to find protein structures and thermodynamics at interfaces and test a possibility for understanding those interactions between nanoparticles and proteins which lead to nanoparticle toxicology through entry into living cells. Stable monomolecular protein films have been made at the air-water interface and, with a specially designed vessel, the substrate changed from that which the air-water interfacial film was deposited. This procedure allows interactions, both chemical and physical, between introduced species and the monomolecular film to be studied by reflectometry. The method is briefly illustrated here with some new results on protein-protein interaction between β-casein and κ-casein at the air-water interface using X-rays. These two proteins are an essential component of the structure of milk. In the experiments reported, specific and directional interactions appear to cause different interfacial structures if first, a β-casein monolayer is attacked by a κ-casein solution compared to the reverse. The additional contrast associated with neutrons will be an advantage here. We then show the first results of experiments on the interaction of a β-casein monolayer with a nanoparticle titanium oxide sol, foreshadowing the study of the nanoparticle 'corona' thought to be important for nanoparticle-cell wall penetration.

  3. Protein interfacial structure and nanotoxicology

    Energy Technology Data Exchange (ETDEWEB)

    White, John W. [Research School of Chemistry, Australian National University, Canberra (Australia)], E-mail: jww@rsc.anu.edu.au; Perriman, Adam W.; McGillivray, Duncan J.; Lin, J.-M. [Research School of Chemistry, Australian National University, Canberra (Australia)

    2009-02-21

    Here we briefly recapitulate the use of X-ray and neutron reflectometry at the air-water interface to find protein structures and thermodynamics at interfaces and test a possibility for understanding those interactions between nanoparticles and proteins which lead to nanoparticle toxicology through entry into living cells. Stable monomolecular protein films have been made at the air-water interface and, with a specially designed vessel, the substrate changed from that which the air-water interfacial film was deposited. This procedure allows interactions, both chemical and physical, between introduced species and the monomolecular film to be studied by reflectometry. The method is briefly illustrated here with some new results on protein-protein interaction between {beta}-casein and {kappa}-casein at the air-water interface using X-rays. These two proteins are an essential component of the structure of milk. In the experiments reported, specific and directional interactions appear to cause different interfacial structures if first, a {beta}-casein monolayer is attacked by a {kappa}-casein solution compared to the reverse. The additional contrast associated with neutrons will be an advantage here. We then show the first results of experiments on the interaction of a {beta}-casein monolayer with a nanoparticle titanium oxide sol, foreshadowing the study of the nanoparticle 'corona' thought to be important for nanoparticle-cell wall penetration.

  4. Dietary protein intake and chronic kidney disease.

    Science.gov (United States)

    Ko, Gang Jee; Obi, Yoshitsugu; Tortorici, Amanda R; Kalantar-Zadeh, Kamyar

    2017-01-01

    High-protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration. This can cause damage to glomerular structure leading to or aggravating chronic kidney disease (CKD). Hence, a low-protein diet (LPD) of 0.6-0.8 g/kg/day is often recommended for the management of CKD. We reviewed the effect of protein intake on incidence and progression of CKD and the role of LPD in the CKD management. Actual dietary protein consumption in CKD patients remains substantially higher than the recommendations for LPD. Notwithstanding the inconclusive results of the 'Modification of Diet in Renal Disease' (MDRD) study, the largest randomized controlled trial to examine protein restriction in CKD, several prior and subsequent studies and meta-analyses appear to support the role of LPD on retarding progression of CKD and delaying initiation of maintenance dialysis therapy. LPD can also be used to control metabolic derangements in CKD. Supplemented LPD with essential amino acids or their ketoanalogs may be used for incremental transition to dialysis especially on nondialysis days. The LPD management in lieu of dialysis therapy can reduce costs, enhance psychological adaptation, and preserve residual renal function upon transition to dialysis. Adherence and adequate protein and energy intake should be ensured to avoid protein-energy wasting. A balanced and individualized dietary approach based on LPD should be elaborated with periodic dietitian counseling and surveillance to optimize management of CKD, to assure adequate protein and energy intake, and to avoid or correct protein-energy wasting.

  5. [Effect of lead on the cardiovascular system].

    Science.gov (United States)

    Zyśko, Dorota; Chlebda, Ewa; Gajek, Jacek

    2004-11-01

    Lead is a metal widely spread in the natural environment. It is strongly toxic, particularly to the peripheral and central nervous systems. The toxic influence on the cardiovascular system is most pronounced in case of higher exposures, where myocardium and the renal circulation are affected, in consequence of which secondary arterial hypertension can develop. It seems that lead affects the cardiovascular system mainly by changing the peripheral autonomic nervous system and leading to chronic neuropathy. Chronic exposure, even to low doses of lead, can impair conduction in myocardium. In order to assess those changes thoroughly prospective studies involving newly employed workers with occupational exposure to toxic activity of lead will be necessary.

  6. Process of Fragment-Based Lead Discovery—A Perspective from NMR

    Directory of Open Access Journals (Sweden)

    Rongsheng Ma

    2016-07-01

    Full Text Available Fragment-based lead discovery (FBLD has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI systems. Nuclear magnetic resonance (NMR spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets.

  7. Mobilized plasma lead as an index of lead body burden and its relation to the heme-related indices.

    Science.gov (United States)

    Sakai, T; Ushio, K; Ikeya, Y

    1998-07-01

    Plasma lead (Pb-P) from workers were distributed in two main fractions: a protein bound fraction and low molecular weight fractions. Lead mobilized into plasma by CaEDTA was mainly observed in the low molecular weight fraction corresponding to lead disodium ethylenediamine tetraacetic acid (PbEDTA). The peak levels of Pb-P was attained around 1.5 and 2.5 hours after the start of CaEDTA injection. Pb-P and blood lead levels (Pb-B) at 2 h after the injection were 4.26 (+/- 2.84) and 0.96 (+/- 0.27) fold of the initial levels just before the injection. Pb-P concentrations at 2 hours after the start of CaEDTA injection (MPb-P) were well correlated (r = 0.740) with amounts of lead excreted in urine for 24 h thereafter (MPb-U). log MPb-P as well as log MPb-U were correlated with Pb-B (r = 0.765 and 0.817, respectively). Correlation coefficients of lead body burden (MPb-P or MPb-U) vs the logarithms of the effect indices (delta-aminolevulinic acid (ALA) dehydratase, ALA in urine, coproporphyrin in urine, and erythrocyte zinc protoporphyrin) were higher than the correlation coefficients of exposure indices (Pb-B or Pb-U) vs the logarithms of the effect indices. Thus the biological effect monitoring is significant and reliable for evaluating the functional components of lead body burden (MPb-P or MPb-U).

  8. High-temperature superconducting current leads

    Science.gov (United States)

    Hull, J. R.

    1992-07-01

    The use of high-temperature superconductors (HTSs) for current leads to deliver power to devices at liquid helium temperature is near commercial realization. The use of HTSs in this application has the potential to reduce refrigeration requirements and helium boiloff to values significantly lower than the theoretical best achievable with conventional leads. Considerable advantage is achieved by operating these leads with an intermediate temperature heat sink. The HTS part of the lead can be made from pressed and sintered powder. Powder-in-tube fabrication is also possible, however, the normal metal part of the lead acts as a thermal short and cannot provide much stabilization without increasing the refrigeration required. Lead stability favors designs with low current density. Such leads can be manufactured with today's technology, and lower refrigeration results from the same allowable burnout time. Higher current densities result in lower boiloff for the same lead length, but bumout times can be very short. In comparing experiment to theory, the density of helium vapor needs to be accounted for in calculating the expected boiloff. For very low-loss leads, two-dimensional heat transfer and the state of the dewar near the leads may play a dominant role in lead performance.

  9. Superconducting lead particles produced by chemical techniques

    Science.gov (United States)

    Fariss, T. L.; Nixon, W. E.; Bucelot, T. J.; Deaver, B. S., Jr.; Mitchell, J. W.

    1982-09-01

    The superconductivity of extremely small lead particles has been studied as a function of size, surface condition, and connectivity using chemical techniques to produce particles of well-controlled size and shape suspended in insulating media. Approximately monodisperse suspensions of equiaxed, rod, and lath-shaped particles of lead halides and other lead compounds suspended in gelatin, polyacrylamide, polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, and hydroxyethyl cellulose have been produced. These particles have been reduced to pseudomorphs of lead in the liquid phase or the suspensions have been coated on substrates and dried before reduction. Reducing solutions containing aminoiminomethanesulfinic acid are effective with particles of lead halides, lead phosphate, lead sulfate, and lead tartrate. Suspensions of smaller discrete lead particles have also been produced by direct reduction of solutions of soluble lead salts containing suitable polymers, chelating, and stabilizing agents. Dispersions with mean particle dimensions between 3 nm and 5 μm, and a narrow size-frequency distribution, have been produced. The superconductivity of the particles has been characterized by measurements of the magnetization as a function of temperature and magnetic field. The larger particles have a transition temperature of 7.2 K, the same as bulk lead; however, for particles of characteristic dimensions less than 20 nm, the transition temperature is lower by ˜0.1 K.

  10. Superconducting lead particles produced by chemical techniques

    International Nuclear Information System (INIS)

    Fariss, T.L.; Nixon, W.E.; Bucelot, T.J.; Deaver, B.S. Jr.; Mitchell, J.W.

    1982-01-01

    The superconductivity of extremely small lead particles has been studied as a function of size, surface condition, and connectivity using chemical techniques to produce particles of well-controlled size and shape suspended in insulating media. Approximately monodisperse suspensions of equiaxed, rod, and lath-shaped particles of lead halides and other lead compounds suspended in gelatin, polyacrylamide, polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, and hydroxyethyl cellulose have been produced. These particles have been reduced to pseudomorphs of lead in the liquid phase or the suspensions have been coated on substrates and dried before reduction. Reducing solutions containing aminoiminomethanesulfinic acid are effective with particles of lead halides, lead phosphate, lead sulfate, and lead tartrate. Suspensions of smaller discrete lead particles have also been produced by direct reduction of solutions of soluble lead salts containing suitable polymers, chelating, and stabilizing agents. Dispersions with mean particle dimensions between 3 nm and 5 μm, and a narrow size-frequency distribution, have been produced. The superconductivity of the particles has been characterized by measurements of the magnetization as a function of temperature and magnetic field. The larger particles have a transition temperature of 7.2 K, the same as bulk lead; however, for particles of characteristic dimensions less than 20 nm, the transition temperature is lower by approx.0.1 K

  11. Association of Lead Levels and Cerebral Palsy

    Science.gov (United States)

    Bansal, Neha; Aggarwal, Anju; Faridi, M. M. A.; Sharma, Tusha; Baneerjee, B. D.

    2017-01-01

    Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children. PMID:28491920

  12. Editorial: Lead Risk Assessment and Health Effects

    Directory of Open Access Journals (Sweden)

    Howard W. Mielke

    2016-06-01

    Full Text Available In 1980, Clair C. Patterson stated: “Sometime in the near future it probably will be shown that the older urban areas of the United States have been rendered more or less uninhabitable by the millions of tons of poisonous industrial lead residues that have accumulated in cities during the past century”. We live in the near future about which this quote expressed concern. This special volume of 19 papers explores the status of scientific evidence regarding Dr. Patterson’s statement on the habitability of the environments of communities. Authors from 10 countries describe a variety of lead issues in the context of large and small communities, smelter sites, lead industries, lead-based painted houses, and vehicle fuel treated with lead additives dispersed by traffic. These articles represent the microcosm of the larger health issues associated with lead. The challenges of lead risk require a concerted global action for primary prevention.

  13. Update on Recovering Lead From Scrap Batteries

    Science.gov (United States)

    Cole, E. R.; Lee, A. Y.; Paulson, D. L.

    1985-02-01

    Previous work at the Bureau of Mines Rolla Research Center, U.S. Department of the Interior, resulted in successful development of a bench-scale, combination electrorefining-electrowinning method for recycling lead from scrap batteries by using waste fluosilicic acid (H2SiF6) as electrolyte.1,2 This paper describes larger scale experiments. Prior attempts to electrowin lead failed because large quantities of insoluble lead dioxide were deposited on the anodes at the expense of lead deposition on the cathodes. A major breakthrough was achieved with the discovery that lead dioxide formation at the anodes is prevented by adding a small amount of phosphorus to the electrolyte. The amount of PbO2 formed on the anodes during lead electrowinning was less than 1% of the total lead deposited on the cathodes. This work recently won the prestigious IR·100 award as one of the 100 most significant technological advances of 1984.

  14. Isotopic analysis of bullet lead samples

    International Nuclear Information System (INIS)

    Sankar Das, M.; Venkatasubramanian, V.S.; Sreenivas, K.

    1976-01-01

    The possibility of using the isotopic composition of lead for the identification of bullet lead is investigated. Lead from several spent bullets were converted to lead sulphide and analysed for the isotopic abundances using an MS-7 mass spectrometer. The abundances are measured relative to that for Pb 204 was too small to permit differentiation, while the range of variation of Pb 206 and Pb 207 and the better precision in their analyses permitted differentiating samples from one another. The correlation among the samples examined has been pointed out. The method is complementary to characterisation of bullet leads by the trace element composition. The possibility of using isotopically enriched lead for tagging bullet lead is pointed out. (author)

  15. Lead sources in human diet in Greenland

    DEFF Research Database (Denmark)

    Bjerregaard, Peter; Johansen, Poul; Mulvad, Gert

    2004-01-01

    Although blood lead levels have declined in Greenland, they are still elevated despite the fact that lead levels in the Greenland environment are very low. Fragments of lead shot in game birds have been suggested as an important source of dietary exposure, and meals of sea birds, particularly eider......, contain high concentrations of lead. In a cross-sectional population survey in Greenland in 1993-1994, blood lead adjusted for age and sex was found to be associated with the reported consumption of sea birds. Participants reporting less than weekly intake of sea birds had blood lead concentrations...... of approximately 75 microg/L, whereas those who reported eating sea birds several times a week had concentrations of approximately 110 microg/L, and those who reported daily intake had concentrations of 170 microg/L (p = 0.01). Blood lead was not associated with dietary exposure to other local or imported food...

  16. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  17. Eryptosis in lead-exposed workers.

    Science.gov (United States)

    Aguilar-Dorado, Itzel-Citlalli; Hernández, Gerardo; Quintanar-Escorza, Martha-Angelica; Maldonado-Vega, María; Rosas-Flores, Margarita; Calderón-Salinas, José-Víctor

    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 64.8μg/dl) and non-exposed workers (4.2μg/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(2+)]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 (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(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. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Association of Lead Levels and Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Neha Bansal MD

    2017-03-01

    Full Text Available Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer. Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001. Among children with cerebral palsy, 19 (55.88% children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029. No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children.

  19. Determining tissue-lead levels in large game mammals harvested with lead bullets: human health concerns.

    Science.gov (United States)

    Tsuji, L J S; Wainman, B C; Jayasinghe, R K; VanSpronsen, E P; Liberda, E N

    2009-04-01

    Recently, the use of lead isotope ratios has definitively identified lead ammunition as a source of lead exposure for First Nations people, but the isotope ratios for lead pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden; however, few studies have determined if lead bullet fragments are present in big game carcasses. We found elevated tissue-lead concentrations (up to 5,726.0 microg/g ww) in liver (5/9) and muscle (6/7) samples of big game harvested with lead bullets and radiographic evidence of lead fragments. Thus, we would advise that the tissue surrounding the wound channel be removed and discarded, as this tissue may be contaminated by lead bullet fragments.

  20. Effects of ionizing radiations on proteins

    International Nuclear Information System (INIS)

    Maire, M. le; Foresta, B. de; Viel, A.; Thauvette, L.; Beauregard, G.; Potier, M.

    1990-01-01

    We have reinvestigated the use of ionizing radiations to measure the molecular mass of water-soluble or membrane proteins. Exposure of purified standard proteins to increasing doses of ionizing radiation causes progressive fragmentation of the native protein into defined peptide patterns. The coloured band corresponding to the intact protein was measured on the SDS gel as a function of dose to determine the dose (D 37.t ) corresponding to 37% of the initial amount of unfragmented protein deposited on the gel. This led to a calibration curve and the known molecular mass of the standard proteins. However, we have to conclude that this method is useless to determine the state of aggregation of a protein, since, for all the oligomers tested, the best fit was obtained by using the protomeric molecular mass, suggesting that there is no energy transfer between protomers. Furthermore, SDS greatly increases the fragmentation rate of proteins, which suggests additional calibration problems for membrane proteins in detergent or in the lipid bilayer. The main drawback of the technique is that some proteins behaved anomalously, leading to very large errors in the apparent target size as compared with true molecular mass. It is thus unreliable to apply the radiation method for absolute molecular-mass determination. We then focused on the novel finding that discrete fragmentation of proteins occurs at preferential sites, and this was studied with aspartate transcarbamylase. (author)

  1. The human protein disulfide isomerase gene family

    Directory of Open Access Journals (Sweden)

    Galligan James J

    2012-07-01

    Full Text Available Abstract Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs. These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX. As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR. Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

  2. The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

    Science.gov (United States)

    Wu, Fan-Lin; Liu, Yin; Jiang, He-Wei; Luan, Yi-Zhao; Zhang, Hai-Nan; He, Xiang; Xu, Zhao-Wei; Hou, Jing-Li; Ji, Li-Yun; Xie, Zhi; Czajkowsky, Daniel M; Yan, Wei; Deng, Jiao-Yu; Bi, Li-Jun; Zhang, Xian-En; Tao, Sheng-Ce

    2017-08-01

    Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Yeast Interacting Proteins Database: YDL239C, YLR423C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...cription Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading

  4. Yeast Interacting Proteins Database: YDL239C, YPL070W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...cription Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading

  5. Yeast Interacting Proteins Database: YDL239C, YML042W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...iption Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading

  6. Yeast Interacting Proteins Database: YDR176W, YDL239C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle pole...ining structure at the leading edge of the prospore membrane via interaction with spindle pole body componen...DY3 Prey description Protein required for spore wall formation, thought to mediate assembly of a Don1p-conta

  7. Yeast Interacting Proteins Database: YDL239C, YKL103C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...ait description Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.Y.; Li, A.J.; Finlow, D.E. [Key Lab of Electrochemical Technology on Energy Storage and Power Generation in Guangdong Universities, School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China)

    2009-06-01

    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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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

  10. Origins of Protein Functions in Cells

    Science.gov (United States)

    Seelig, Burchard; Pohorille, Andrzej

    2011-01-01

    In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis and in vitro evolution of very large libraries of random amino acid sequences. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions yet, important clues have been uncovered. In one example (Keefe and Szostak, 2001), novel ATP binding proteins were identified that appear to be unrelated in both sequence and structure to any known ATP binding proteins. One of these proteins was subsequently redesigned computationally to bind GTP through introducing several mutations that introduce targeted structural changes to the protein, improve its binding to guanine and prevent water from accessing the active center. This study facilitates further investigations of individual evolutionary steps that lead to a change of function in primordial proteins. In a second study (Seelig and Szostak, 2007), novel enzymes were generated that can join two pieces of RNA in a reaction for which no natural enzymes are known

  11. Bulk diffusion and solubility of silver and nickel in lead, lead-silver and lead-nickel solid solutions

    International Nuclear Information System (INIS)

    Amenzou-Badrour, H.; Moya, G.; Bernardini, J.

    1988-01-01

    The results of a study of solubility and bulk diffusion of /sup 110/Ag and /sup 63/Ni in lead, lead-silver and lead-nickel solid solutions in the temperature range 220 to 88 0 C are reported. Owing to the low solubility of silver and nickel in lead, Fick's solution corresponding to the boundary condition of a constant concentration of solute at the surface has been used. Depth profile concentration analysis suggests a fundamental difference between the diffusion mechanisms of silver and nickel. Since silver penetration profiles in pure lead give diffusion coefficients independent of the penetration depth and silver concentration, it is suggested that slight decreases of silver diffusivity in lead-silver solid solutions have no significance. This implies that the interstitial silver atoms do not associate significantly with each other to form Ag-Ag dimers. In contrast, different behaviors of /sup 63/Ni depth profile concentration in pure lead and saturated PbNi solid solutions agree with a Ni-Ni interaction leading to the formation of less mobile dimers near the surface in pure lead

  12. Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox.

    Science.gov (United States)

    Leveridge, Melanie; Chung, Chun-Wa; Gross, Jeffrey W; Phelps, Christopher B; Green, Darren

    2018-06-01

    There has been much debate around the success rates of various screening strategies to identify starting points for drug discovery. Although high-throughput target-based and phenotypic screening has been the focus of this debate, techniques such as fragment screening, virtual screening, and DNA-encoded library screening are also increasingly reported as a source of new chemical equity. Here, we provide examples in which integration of more than one screening approach has improved the campaign outcome and discuss how strengths and weaknesses of various methods can be used to build a complementary toolbox of approaches, giving researchers the greatest probability of successfully identifying leads. Among others, we highlight case studies for receptor-interacting serine/threonine-protein kinase 1 and the bromo- and extra-terminal domain family of bromodomains. In each example, the unique insight or chemistries individual approaches provided are described, emphasizing the synergy of information obtained from the various tactics employed and the particular question each tactic was employed to answer. We conclude with a short prospective discussing how screening strategies are evolving, what this screening toolbox might look like in the future, how to maximize success through integration of multiple tactics, and scenarios that drive selection of one combination of tactics over another.

  13. Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations.

    Directory of Open Access Journals (Sweden)

    Lydia Chang

    Full Text Available Ubiquilin proteins facilitate delivery of ubiquitinated proteins to the proteasome for degradation. Interest in the proteins has been heightened by the discovery that gene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS. However, the mechanisms by which the mutations cause ALS are not known. Here we report on the underlying defect of ubiquilin-2 proteins containing ALS-linked mutations in affecting proteasome-mediated degradation. We found that overexpression of ubiquilin-2 proteins containing any one of five different ALS mutations slow degradation of Myc, a prototypic proteasome substrate. Examination of coprecipitating proteins indicated that the mutant proteins are generally capable of binding polyubiquitinated proteins, but defective in binding the proteasome. GST-pulldown studies revealed that many of the mutants bind weaker to the S5a subunit of the proteasome, compared with wild type (WT ubiquilin-2 protein. The results suggest the mutant proteins are unable to deliver their captured cargo to the proteasome for degradation, which presumably leads to toxicity. Quantification of cell death is consistent with this idea. Measurement of protein turnover further indicated the mutant proteins have longer half-lives than WT ubiquilin-2. Our studies provide novel insight into the mechanism by which ALS-linked mutations in UBQLN2 interfere with protein degradation.

  14. Lead in soils, plants and animals

    Energy Technology Data Exchange (ETDEWEB)

    Scheltinga, H

    1955-01-01

    The toxicity of lead for plants is small, except in the case of water cultures. Animals can absorb more lead without toxic effect than was previously expected. This applies to acute poisoning as well as chronic poisoning. As a result of experiments over many years (Allcroft and Blaxter, 1950) the possibility of chronic lead poisoning has been found to be minute. Rations containing 240 mg lead/kg dried fodder, given daily over a period of three years, did not cause any poisoning at all in cattle thus fed. Where lead poisoning did take place, it was observed that the ratio of lead in the dried fodder was > 1000 mg/kg; the proportion was generally much higher. In normal cases grass contains only 5 to 15 mg lead/kg. The total lead content of samples from arable land was 10 to 25 mg/kg soil. For grassland on peat or clay the amount was slightly higher. The influence on the lead status of soils and plants of fertilizing with compost or copper slag flour, both containing a small percentage of lead, proved to be negligible. It is definite that in normal use, these fertilizers cannot cause any danger for either plant or animal. 24 references, 3 tables.

  15. Exposure to lead from intake of coffee

    DEFF Research Database (Denmark)

    Hansen, Max; Sloth, Jens Jørgen; Rasmussen, Rie Romme

    Food and beverages is one of the primary sources of intake of and exposure to lead, with beverages accounting for almost 50%. Previous studies from Denmark have estimated that the intake of lead from coffee is very high and may contribute to up to 20% of the total lead intake from food and bevera......Food and beverages is one of the primary sources of intake of and exposure to lead, with beverages accounting for almost 50%. Previous studies from Denmark have estimated that the intake of lead from coffee is very high and may contribute to up to 20% of the total lead intake from food...... and beverages. This estimate is, however, based on older, non-published data. In the current project extensive chemical analyses of coffee beans, drinking water and ready-to-drink coffee have been performed. The results hereof have been compared to calculations of the total intake of lead from food...... and beverages. The results show that the intake of lead from coffee is considerably lower than previously estimated and account for 4.2% and 3.3% of the total lead intake from food and beverages for Danish men and women, respectively. It can generally be concluded that the intake of lead from coffee is low...

  16. Air pollution from lead added to gasoline

    Energy Technology Data Exchange (ETDEWEB)

    Dingeon, B; Collombel, C

    1973-01-01

    General hygienic and toxicological problems of lead added to gasoline are discussed. Lead emitted by motor vehicles pollutes the air especially in cities and along highways, and is accumulated by soil and plants. The lead levels found in the blood of subjects living in cities and near highways was significantly higher than in rural dwellers. Close correlation between the atmospheric lead concentration and the carbon monoxide concentration as well as the traffic density was established, indicating traffic as the source of atmospheric lead. The effect of traffic on the atmospheric lead concentration extended over a distance of up to 4 km. The lead, emitted by motor vehicles in the form of submicron particles, is retained in the organism at rates of 5-10 percent following ingestion, and at rates of 30-50 percent when inhaled. Lead is partially excreted by the liver, kidney, hair, and nails. Some 95 percent of the retained lead is found in the blood, and accumulation in the bones with potential mobilization due to increases in the corticosteroid level was observed. Exposure to lead can be diagnosed by basophil granulation test, urine delta-aminolevulinic acid test, and delta-aminolevulinic acid dehydratase test.

  17. Lead contamination of paint remediation workers' vehicles.

    Science.gov (United States)

    Boraiko, Carol; Wright, Eva M; Ralston, Faye

    2013-03-01

    Exposure to lead has been shown to be harmful to adults; it is a teratogen, it can damage the peripheral nervous system, and it adversely affects the reproductive system. Professional lead-based paint remediation workers are at risk of exposure to lead dust. The authors' study was conducted to determine if these remediation workers transfer lead from their work site to their vehicles and then potentially expose their families. It was hypothesized that remediation workers transported the lead from the remediation work site to the floorboards of their vehicles due to not following required protective equipment use. The laboratory's level of quantitation for lead on the wipe samples, 10 microg/ft2, was used to indicate lead contamination. This level was exceeded in 50% of the floorboards sampled. These results confirm that many vehicle floorboards used by remediation workers are contaminated with lead dust, potentially resulting in transfer of lead dust. The ultimate detrimental outcome could be the transfer of lead particles to other family members, causing the poisoning of a child or other at-risk person.

  18. Impacts of aerosol lead to natural ecosystems

    International Nuclear Information System (INIS)

    Murozumi, Masayo; Nakamura, Seiji; Yoshida, Katsumi

    1982-01-01

    Impacts of aerosol lead have changed the concentration and isotopic ratios of the element circulating in remote ecosystems in the Hidaka and Tarumae mountains. Concentrations of lead in successive each 10 years ring veneer of Cercidiphyllum Japonica show that amount of the element residing on the bark and supwood layers has increased by a factor of 2 or more in comparison with that of the core part. The isotopic ratios of lead in the basement rocks and soils under the ecosystems converge to a certain narrow spot along the isochron Iine of the element, and distinguish their geochronogical characteristics from other leads of different sources. In these ecosystems, however, the lead isotopic ratios of materials exposed to the atmosphere are similar to those of foreign and anthropogenic aerosol lead but are evidently dissimilar to those of the rocks and soils. Furthermore, the lead isotopic ratios in yearly ring veneers of Ceridiphyllum Japonica and Ostrya Japonica show a certain differentiation towards the bark from the core, i.e., an approach to those of anthropogenic aerosol lead from those of the basement rocks and soils, as listed in Table 7. The lead burden per hectare in these remote ecosystems has increased to 4 g by the impact of 2 g of aerosol lead. (author)

  19. Lead exposures from varnished floor refinishing.

    Science.gov (United States)

    Schirmer, Joseph; Havlena, Jeff; Jacobs, David E; Dixon, Sherry; Ikens, Robert

    2012-01-01

    We evaluated the presence of lead in varnish and factors predicting lead exposure from floor refinishing and inexpensive dust suppression control methods. Lead in varnish, settled dust, and air were measured using XRF, laboratory analysis of scrape and wipe samples, and National Institute for Occupational Safety and Health (NIOSH) Method 7300, respectively, during refinishing (n = 35 homes). Data were analyzed using step-wise logistic regression. Compared with federal standards, no lead in varnish samples exceeded 1.0 mg/cm(2), but 52% exceeded 5000 ppm and 70% of settled dust samples after refinishing exceeded 40 μg/ft(2). Refinishing pre-1930 dwellings or stairs predicted high lead dust on floors. Laboratory analysis of lead in varnish was significantly correlated with airborne lead (r = 0.23, p = 0.014). Adding dust collection bags into drum sanders and HEPA vacuums to edgers and buffers reduced mean floor lead dust by 8293 μg Pb/ft(2) (pairborne lead exposures to less than 50 μg/m(3). Refinishing varnished surfaces in older housing produces high but controllable lead exposures.

  20. The E5 Proteins

    OpenAIRE

    DiMaio, Daniel; Petti, Lisa

    2013-01-01

    The E5 proteins are short transmembrane proteins encoded by many animal and human papillomaviruses. These proteins display transforming activity in cultured cells and animals, and they presumably also play a role in the productive virus life cycle. The E5 proteins are thought to act by modulating the activity of cellular proteins. Here, we describe the biological activities of the best-studied E5 proteins and discuss the evidence implicating specific protein targets and pathways in mediating ...

  1. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  2. EDITORIAL: Precision proteins Precision proteins

    Science.gov (United States)

    Demming, Anna

    2010-06-01

    Since the birth of modern day medicine, during the times of Hippocrates in ancient Greece, the profession has developed from the rudimentary classification of disease into a rigorous science with an inspiring capability to treat and cure. Scientific methodology has distilled clinical diagnostic tools from the early arts of prognosis, which used to rely as much on revelation and prophecy, as intuition and judgement [1]. Over the past decade, research into the interactions between proteins and nanosystems has provided some ingenious and apt techniques for delving into the intricacies of anatomical systems. In vivo biosensing has emerged as a vibrant field of research, as much of medical diagnosis relies on the detection of substances or an imbalance in the chemicals in the body. The inherent properties of nanoscale structures, such as cantilevers, make them well suited to biosensing applications that demand the detection of molecules at very low concentrations. Measurable deflections in cantilevers functionalised with antibodies provide quantitative indicators of the presence of specific antigens when the two react. Such developments have roused mounting interest in the interactions of proteins with nanostructures, such as carbon nanotubes [3], which have demonstrated great potential as generic biomarkers. Plasmonic properties are also being exploited in sensing applications, such as the molecular sentinel recently devised by researchers in the US. The device uses the plasmonic properties of a silver nanoparticle linked to a Raman labelled hairpin DNA probe to signal changes in the probe geometry resulting from interactions with substances in the environment. Success stories so far include the detection of two specific genes associated with breast cancer [4]. A greater understanding of how RNA interference regulates gene expression has highlighted the potential of using this natural process as another agent for combating disease in personalized medicine. However, the

  3. Evolvability of thermophilic proteins from archaea and bacteria.

    Science.gov (United States)

    Takano, Kazufumi; Aoi, Atsushi; Koga, Yuichi; Kanaya, Shigenori

    2013-07-16

    Proteins from thermophiles possess high thermostability. The stabilization mechanisms differ between archaeal and bacterial proteins, whereby archaeal proteins are mainly stabilized via hydrophobic interactions and bacterial proteins by ion pairs. High stability is an important factor in promoting protein evolution, but the precise means by which different stabilization mechanisms affect the evolution process remain unclear. In this study, we investigated a random mutational drift of esterases from thermophilic archaea and bacteria at high temperatures. Our results indicate that mutations in archaeal proteins lead to improved function with no loss of stability, while mutant bacterial proteins are largely destabilized with decreased activity at high temperatures. On the basis of these findings, we suggest that archaeal proteins possess higher "evolvability" than bacterial proteins under temperature selection and are additionally able to evolve into eukaryotic proteins.

  4. The refining of secondary lead for use in advanced lead-acid batteries

    International Nuclear Information System (INIS)

    Ellis, Timothy W.; Mirza, Abbas H.

    2010-01-01

    Secondary lead, i.e. material produced by the recycling of lead-acid batteries has become the primary source of lead in much of the world. This has been important to the secondary lead industry as other uses have dwindled, e.g. lead based pigments, chemicals, fuel additives, solders and CRT glasses. Presently, battery manufacturing accounts for greater than 80% of lead consumption while recycled lead accounts for approximately the same market share of lead supply. These two facts strongly demonstrate the battery manufacturing and recycled lead are intimately coupled in everyday life. In this paper we will explore how recycled lead has become the material of choice for battery construction through the development of a recovery and refining process that exceeds the industries requirements. Particular focus will be on addressing the results presented by Prengaman on the effects of contaminant or tramp elements on gassing in lead-acid batteries. (author)

  5. High human exposure to lead through consumption of birds hunted with lead shot

    International Nuclear Information System (INIS)

    Johansen, P.; Asmund, G.; Riget, F.

    2004-01-01

    Lead shot contaminates the edible parts of birds so that tolerable human lead intake is exceeded. - We assess lead contamination of Greenland seabirds killed with lead shot having studied thick-billed murre and common eider, the two most important species in the diet. The lead concentration is very high in meat of eiders killed with lead shot (mean 6.1 μg/g-wet wt, 95% CL 2.1-12). This level is about 44 times higher than in drowned eiders and eight times higher than in shot murres. Analyzing whole breasts instead of sub-samples reveals about seven times higher lead levels in birds' meat. We conclude that in some cases the lead intake by Greenland bird eaters will largely exceed the FAO/WHO tolerable lead intake guideline and that lead shot is a more important source of lead in the diet than previously estimated

  6. Lead pollution: lead content in milk from cows fed on contaminated forages

    Energy Technology Data Exchange (ETDEWEB)

    Sapetti, C; Arduino, E; Durio, P

    1973-01-01

    Lead toxicity is reviewed, and the history of the lead poisoning is described. Much of the lead pollution in soil is due to automobile exhaust. Two milk cows were fed forage with added lead acetate. The 20 kg of lead corresponded to 50 ppm, a level that is often found in hays near major highways. The cows milk was then analyzed for lead content. During the first and second phase of administration of lead salts, the milk cows did not show any evident symptoms of intoxication. The lead in the milk did have a marked correlation with the administered lead. The lead doses did not last long enough for chronic symptoms to begin. The dosage of lead in milk, due to the facility of drawing samples and the relevant levels of response, could represent a valid method for diagnosing incipient chronic intoxications.

  7. Assessing the Accuracy of Ancestral Protein Reconstruction Methods

    OpenAIRE

    Williams, Paul D; Pollock, David D; Blackburne, Benjamin P; Goldstein, Richard A

    2006-01-01

    The phylogenetic inference of ancestral protein sequences is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Every inference method leads to errors in the ancestral protein sequence, resulting in potentially misleading estimates of the ancestral protein's properties. To assess the accuracy of ancestral protein reconstruction methods, we performed computational population evolu...

  8. Isolation of radioactive thallium from lead targets

    International Nuclear Information System (INIS)

    Kozlova, M.D.; Sevast'yanova, A.S.; Malinin, A.B.; Kurenkov, N.V.

    1989-01-01

    Two methods of thallium-201 preperation from Pb-targets irradiated with protons: precipitation-extraction (1) and extraction (2) - are developed. When the target irraiated is extracted during the time necessary for bismuth-201 transformation into lead-201, lead macroquantity containing lead-201 was separated from undesirable thallium radionuclides, which are formed in direct nuclear reactions. The lead fraction was extracted to accumulate thallium-201, and it was separated from lead mocroquantity. The target was dissolved in the nitric acid. The 1st method differs from the 2nd one by the fact that before thallium-201 extraction, lead was precipitaed by the nitric acid. The 1st method permits to separate thallium-201 with chemical yield not less than 90 %, the 2nd one - ≥95 %. 2 refs

  9. Narrow Lead Aprons under Medical Fluoroscopy Procedures

    International Nuclear Information System (INIS)

    Ben-Shlomo, A.

    2014-01-01

    Lead aprons are the major protective item of the medical staff whose work involves x-ray exposure. Heart catheterization and angiography procedures represent the most common exposures of the medical staff. The lead equivalent thickness of lead aprons worn by the medical staff is defined by many national standards. The frontal side of the aprons should be 0.25 mm lead equivalent at working conditions under 100 kV, 0.35 mm for working conditions above 100 kV, and 0.5 mm for heart catheterization and angiography. The back side of the body needs less protection and usually is covered by 0.25 mm of lead equivalent. The lead equivalent thickness is defined at the 80 kV level

  10. A review of lead poisoning in swans

    Science.gov (United States)

    Blus, L.J.

    1994-01-01

    Nearly 10,000 swans of six species or subspecies from 14 countries have died from poisoning caused by lead that originated from ingestion of fishing weights, shotgun pellets (shot), or contaminated vegetation or sediments associated with mining and smelting wastes. Lead contamination in mute swans in England caused local population declines during the late 1970s and 1980s. More tundra swans died from lead poisoning than any other species. The extreme record involved an estimated 7200 tundra swans that died over five winters at one locality in North Carolina. The recent legislation to ban lead fishing weights in most of England and Wales and recent replacement of lead shot with steel shot for waterfowl hunting in the United States and a few areas of Europe, including Denmark, are expected to reduce the incidence of lead poisoning in swans.

  11. Radiation effects on lead silicate glass surfaces

    International Nuclear Information System (INIS)

    Wang, P.W.; Zhang, L.P.; Borgen, N.; Pannell, K.

    1996-01-01

    Radiation-induced changes in the microstructure of lead silicate glass were investigated in situ under Mg K α irradiation in an ultra-high vacuum (UHV) environment by X-ray photoelectron spectroscopy (XPS). Lead-oxygen bond breaking resulting in the formation of pure lead was observed. The segregation, growth kinetics and the structural relaxation of the lead, with corresponding changes in the oxygen and silicon on the glass surfaces were studied by measuring the time-dependent changes in concentration, binding energy shifts, and the full width at half maximum. A bimodal distribution of the oxygen XPS signal, caused by bridging and non-bridging oxygens, was found during the relaxation process. All experimental data indicate a reduction of the oxygen concentration, a phase separation of the lead from the glass matrix, and the metallization of the lead occurred during and after the X-ray irradiation. (author)

  12. 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.

  13. 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.)

  14. Lead in Glasgow street dirt and soil

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, J G [Univ. of Glasgow; Lyon, T D.B.

    1977-07-01

    The levels of lead in city street dirt and in soil from various locations in Glasgow were investigated during spring 1976. Lead concentrations in street dirt ranged from 150 to 2300 ppM, mean 960 ppM, and were significantly elevated with respect to the observed ''natural'' level of 78 ppM. Lead derived from anti-knock compounds in petrol and introduced to the environment via automobile exhausts was clearly implicated as the main source of lead pollution in a series of soil lead measurements at the centre and periphery of eight Glasgow parks. Various chemical leaching techniques were employed and compared. Less than 5 percent of street dirt and soil lead was found to be associated with the organic phase.

  15. Potential disruption of protein-protein interactions by graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mei [Department of Physics, Institute of Quantitative Biology, Zhejiang University, Hangzhou 310027 (China); Kang, Hongsuk; Luan, Binquan [Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Yang, Zaixing [Institute of Quantitative Biology and Medicine, SRMP and RAD-X, and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123 (China); Zhou, Ruhong, E-mail: ruhong@us.ibm.com [Department of Physics, Institute of Quantitative Biology, Zhejiang University, Hangzhou 310027 (China); Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Department of Chemistry, Columbia University, New York, New York 10027 (United States)

    2016-06-14

    Graphene oxide (GO) is a promising novel nanomaterial with a wide range of potential biomedical applications due to its many intriguing properties. However, very little research has been conducted to study its possible adverse effects on protein-protein interactions (and thus subsequent toxicity to human). Here, the potential cytotoxicity of GO is investigated at molecular level using large-scale, all-atom molecular dynamics simulations to explore the interaction mechanism between a protein dimer and a GO nanosheet oxidized at different levels. Our theoretical results reveal that GO nanosheet could intercalate between the two monomers of HIV-1 integrase dimer, disrupting the protein-protein interactions and eventually lead to dimer disassociation as graphene does [B. Luan et al., ACS Nano 9(1), 663 (2015)], albeit its insertion process is slower when compared with graphene due to the additional steric and attractive interactions. This study helps to better understand the toxicity of GO to cell functions which could shed light on how to improve its biocompatibility and biosafety for its wide potential biomedical applications.

  16. Potential disruption of protein-protein interactions by graphene oxide

    International Nuclear Information System (INIS)

    Feng, Mei; Kang, Hongsuk; Luan, Binquan; Yang, Zaixing; Zhou, Ruhong

    2016-01-01

    Graphene oxide (GO) is a promising novel nanomaterial with a wide range of potential biomedical applications due to its many intriguing properties. However, very little research has been conducted to study its possible adverse effects on protein-protein interactions (and thus subsequent toxicity to human). Here, the potential cytotoxicity of GO is investigated at molecular level using large-scale, all-atom molecular dynamics simulations to explore the interaction mechanism between a protein dimer and a GO nanosheet oxidized at different levels. Our theoretical results reveal that GO nanosheet could intercalate between the two monomers of HIV-1 integrase dimer, disrupting the protein-protein interactions and eventually lead to dimer disassociation as graphene does [B. Luan et al., ACS Nano 9(1), 663 (2015)], albeit its insertion process is slower when compared with graphene due to the additional steric and attractive interactions. This study helps to better understand the toxicity of GO to cell functions which could shed light on how to improve its biocompatibility and biosafety for its wide potential biomedical applications.

  17. Petrol with isotopically differentiated lead added

    International Nuclear Information System (INIS)

    Magi, F.; Facchetti, S.; Garibaldi, P.

    1975-01-01

    An experiment is proposed aimed at determining the role of motor traffic in the pollution of the environment by lead, in particular of air, soil, vegetation, food and the human body. The technique of determining the isotopic composition of lead, used in the right way, should enable the whole problem to be solved. It is intended to add lead with a constant isotopic composition different from that of normally occuring lead, whether natural in origin or otherwise, to petrol in at least two regions of Italy. Analyses of lead samples taken from the principal mines have shown that Australian lead (Broken Hill Mine) has quite a different isotopic composition. This lead will therefore be used to prepare the antiknock additives for petrol sold in the regions in question. Adequate sampling should make it possible to determine the contribution to pollution of lead from motor vehicle exhausts. The regions chosen for the experiment are Piedmont (city and province of Turin) and Sardinia (city and province of Cagliari) - the first because of its high traffic density and level of industrialization, the second because of its remoteness and the lead content of the soil, which may affect food. Both regions present favourable conditions for supplying petrol of the intended type. The experiment is intended to last three years; the petrol with Australian lead will be marketed for a period of 18 months. The first results of analyses of the isotopic composition of lead contained in atmospheric dust in the city of Turin and of lead from a number of blood samples are reported in the paper

  18. Verification of radiation exposure using lead shields

    International Nuclear Information System (INIS)

    Hayashida, Keiichi; Yamamoto, Kenyu; Azuma, Masami

    2016-01-01

    A long time use of radiation during IVR (intervention radiology) treatment leads up to an increased exposure on IVR operator. In order to prepare good environment for the operator to work without worry about exposure, the authors examined exposure reduction with the shields attached to the angiography instrument, i. e. lead curtain and lead glass. In this study, the lumber spine phantom was radiated using the instrument and the radiation leaked outside with and without shields was measured by the ionization chamber type survey meter. The meter was placed at the position which was considered to be that for IVR operator, and changed vertically 20-100 cm above X-ray focus by 10 cm interval. The radiation at the position of 80 cm above X-ray focus was maximum without shield and was hardly reduced with lead curtain. However, it was reduced with lead curtain plus lead glass. Similar reduction effects were observed at the position of 90-100 cm above X-ray focus. On the other hand, the radiation at the position of 70 cm above X-ray focus was not reduced with either shield, because that position corresponded to the gap between lead curtain and lead glass. The radiation at the position of 20-60 cm above X-ray focus was reduced with lead curtain, even if without lead glass. These results show that lead curtain and lead glass attached to the instrument can reduce the radiation exposure on IVR operator. Using these shields is considered to be one of good means for IVR operator to work safely. (author)

  19. Forecasting Irish Inflation: A Composite Leading Indicator

    OpenAIRE

    Quinn, Terry; Mawdsley, Andrew

    1996-01-01

    This paper presents the results of research into the construction of a composite leading indicator of the Irish rate of inflation, as measured by the annual percentage change in the Consumer Price Index (CPI). It follows the work of Fagan and Fell (1994) who applied the business cycle leading indicator methodology, initially established by Mitchell and Burns (1938,1946), to construct a composite leading indicator of the Irish business cycle.

  20. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

    Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  1. Protein docking prediction using predicted protein-protein interface.

    Science.gov (United States)

    Li, Bin; Kihara, Daisuke

    2012-01-10

    Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm), is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  2. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    DEFF Research Database (Denmark)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah

    2016-01-01

    ’s disease (PD), Alzheimer’s disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other......In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post......-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially...

  3. Load Dependent Lead Times and Sustainability

    DEFF Research Database (Denmark)

    Pahl, Julia; Voss, Stefan

    2016-01-01

    to prevent decreased quality or waste of production parts and products. This gains importance because waiting times imply longer lead times charging the production system with work in process inventories. Longer lead times can lead to quality losses due to depreciation, so that parts need to be reworked...... if possible or discarded. But return flows of products for rework or remanufacturing actions significantly complicate the production planning process. We analyze sustainability options with respect to lead time management by formulating a comprehensive mathematical model. We consider a deterministic, mixed...

  4. Moveable Leading Edge Device for a Wing

    Science.gov (United States)

    Pitt, Dale M. (Inventor); Eckstein, Nicholas Stephen (Inventor)

    2013-01-01

    A method and apparatus for managing a flight control surface system. A leading edge section on a wing of an aircraft is extended into a deployed position. A deformable section connects the leading edge section to a trailing section. The deformable section changes from a deformed shape to an original shape when the leading edge section is moved into the deployed position. The leading edge section on the wing is moved from the deployed position to an undeployed position. The deformable section changes to the deformed shape inside of the wing.

  5. Lead in some food crops and trees

    Energy Technology Data Exchange (ETDEWEB)

    Warren, H V; Delavault, R E

    1962-02-01

    An investigation has been made of the lead content of trees and some of the more common vegetables and cereals (maize, cabbage, potatoes, carrots, beets, onions, peas, hops, oats, rhubarb, lettuce, cauliflower, leeks, barley, rye, and wheat) grown in British Columbia and in Great Britain. The lead content of the lime, yew, willow, birch, oak, ash, hazel and cypress was determined. It was concluded that in areas where soils have an abnormally high lead content, food products may acquire up to ten times as much lead, or more, than those grown on normal soil.

  6. Lead level in mallard (Anas platyrhynchos

    Directory of Open Access Journals (Sweden)

    Ioan Macinic

    2012-12-01

    Full Text Available The study was carried out on a hunting ground belonging to AJVPS Arad, county Arad. Lead (Pb was determined in Mallard (Anas platyrhynchos tissues (muscles and organs (liver, kidneys to see the contamination level of this tissues and organs and also the impact on humans health because in our days more and more wild game meat take a increasing percentage in humans food ratio. The Mallard is one of the most widespread duck species. Mallard has 50-62 cm length, 800-1400 g weight and lives about 11 years. It prefers rivers and shallow pounds with a lot of reed. It is a migratory species that is flying long distances to find food and unfrozen water, so it is a exposed to lead contamination that is under dust form in atmosphere. But another reason why lead level in Mallard can be higher that in other flying specie (pheasant, woodcock, quail, and pigeons are the lead shot shells that are used for duck hunting. It is known that the ducks can ingest these lead shot shells and so they are often exposed to lead intoxications. This is why in our days more ammunition for waterfowl are steel made or different type of alloys. Lead is known to be one of the most common pollutants with a large range of effects on human health: lead affects nervous system, digestive tract, kidneys, bones, enzymes. Lead has also mutagenic effect, carcinogenic effect, teratogenic effect.

  7. Production Planning with Load Dependent Lead Times

    DEFF Research Database (Denmark)

    Pahl, Julia

    2005-01-01

    Lead times impact the performance of the supply chain significantly. Although there is a large literature concerning queuing models for the analysis of the relationship between capacity utilization and lead times, and there is a substantial literature concerning control and order release policies...... that take lead times into consideration, there have been only few papers describing models at the aggregate planning level that recognize the relationship between the planned utilization of capacity and lead times. In this paper we provide an in-depth discussion of the state-of-the art in this literature......, with particular attention to those models that are appropriate at the aggregate planning level....

  8. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

    2009-06-01

    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  9. Introduction to protein blotting.

    Science.gov (United States)

    Kurien, Biji T; Scofield, R Hal

    2009-01-01

    Protein blotting is a powerful and important procedure for the immunodetection of proteins following electrophoresis, particularly proteins that are of low abundance. Since the inception of the protocol for protein transfer from an electrophoresed gel to a membrane in 1979, protein blotting has evolved greatly. The scientific community is now confronted with a variety of ways and means to carry out this transfer.

  10. Development of the protein crystallography by synchrotron radiation

    International Nuclear Information System (INIS)

    Yamamoto, Masaki

    2014-01-01

    Since crystal structure determination of the first protein by Kendrew in 1959, protein crystallography developed into the leading role of the protein structure study by various technology developments. Especially the utilization of synchrotron radiation from the 1990s brought innovative progress of protein crystallography on the data quality and the phasing method and had expanded the samples targets including membrane proteins and suprarmolecular complexes. Here I give the outline of the history and the future prospects of the protein crystallography from the role of synchrotron radiation. (author)

  11. Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius)

    Science.gov (United States)

    Hoffman, D.J.; Franson, J.C.; Pattee, O.H.; Bunck, C.M.; Murray, H.C.

    1985-01-01

    1. One-day old American kestrel (Faico sparverius) nestlings were orally dosed daily with 5 μl/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days.2. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell (δ-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups.3. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered.4. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development.5. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.

  12. Our interests in protein-protein interactions

    Indian Academy of Sciences (India)

    protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

  13. Acute morphological and physiological effects of lead in the neotropical fish Prochilodus lineatus

    Directory of Open Access Journals (Sweden)

    C. B. R. Martinez

    Full Text Available The present study investigated lead effects on gill morphology, hematocrit, blood sodium, glucose, lipids, protein, and cholesterol of Prochilodus lineatus exposed to two sublethal lead concentrations for 96 h. Preliminary series of short-term static toxicity tests were run to determine LC50 (96 h of lead in P. lineatus, which was 95 mg Pb.L-1. Therefore, lead concentrations tested in the sublethal experiments were 24 and 71 mg Pb.L-1, which correspond to 25% and 75% of the LC50 (96 h, respectively. Gills of P. lineatus exposed to both lead concentrations during 96 h presented a higher occurrence of histopathological lesions such as epithelial lifting, hyperplasia, and lamellar aneurism. P. lineatus did not show significant alterations in hematocrit during exposure to both lead concentrations. Fish exposed to the highest lead concentration showed a significant decrease in Na+ plasma concentration after 48 h, possibly reflecting a sodium influx rate decrease. P. lineatus exposed to both lead concentrations presented a "classical general adaptation syndrome to stress", as hyperglycemia associated with lowered lipids and proteins was reported. Stress-response magnitude was dose-dependent. While the response to the lowest lead concentration might represent adaptation, the highest concentration seems to characterize exhaustion.

  14. Biospecific protein immobilization for rapid analysis of weak protein interactions using self-interaction nanoparticle spectroscopy.

    Science.gov (United States)

    Bengali, Aditya N; Tessier, Peter M

    2009-10-01

    "Reversible" protein interactions govern diverse biological behavior ranging from intracellular transport and toxic protein aggregation to protein crystallization and inactivation of protein therapeutics. Much less is known about weak protein interactions than their stronger counterparts since they are difficult to characterize, especially in a parallel format (in contrast to a sequential format) necessary for high-throughput screening. We have recently introduced a highly efficient approach of characterizing protein self-association, namely self-interaction nanoparticle spectroscopy (SINS; Tessier et al., 2008; J Am Chem Soc 130:3106-3112). This approach exploits the separation-dependent optical properties of gold nanoparticles to detect weak self-interactions between proteins immobilized on nanoparticles. A limitation of our previous work is that differences in the sequence and structure of proteins can lead to significant differences in their affinity to adsorb to nanoparticle surfaces, which complicates analysis of the corresponding protein self-association behavior. In this work we demonstrate a highly specific approach for coating nanoparticles with proteins using biotin-avidin interactions to generate protein-nanoparticle conjugates that report protein self-interactions through changes in their optical properties. Using lysozyme as a model protein that is refractory to characterization by conventional SINS, we demonstrate that surface Plasmon wavelengths for gold-avidin-lysozyme conjugates over a range of solution conditions (i.e., pH and ionic strength) are well correlated with lysozyme osmotic second virial coefficient measurements. Since SINS requires orders of magnitude less protein and time than conventional methods (e.g., static light scattering), we envision this approach will find application in large screens of protein self-association aimed at either preventing (e.g., protein aggregation) or promoting (e.g., protein crystallization) these

  15. EMERGING TECHNOLOGY BULLETIN: RECLAMATION OF LEAD FROM SUPERFUND WASTE MATERIAL USING SECONDARY LEAD SMELTERS

    Science.gov (United States)

    This process involves incorporating lead-contaminated Superfund waste with the regular feed to a secondary lead smelter. Since secondary lead smelters already recover lead from recycled automobile batteries, it seems likely that this technology could be used to treat waste from ...

  16. Lead dust in Broken Hill homes: effect of remediation on indoor lead levels.

    Science.gov (United States)

    Boreland, F; Lyle, D M

    2006-02-01

    This study was undertaken to determine whether home remediation effectively reduced indoor lead levels in Broken Hill, a long-established silver-lead-zinc mining town in outback Australia. A before-after study of the effect of home remediation on indoor lead levels was embedded into a randomized controlled trial of the effectiveness of remediation for reducing elevated blood lead levels in young children. Moist towelettes were used to measure lead loading (microg/m2) on internal windowsills and internal and entry floors of 98 homes; samples were collected before, immediately after, and 2, 4, 6, 8, and 10 months after remediation. Data were log(10) transformed for the analysis. Remediation reduced average indoor lead levels by approximately 50%, and lead levels remained low for the duration of the follow-up period (10 months). The greatest gains were made in homes with the highest initial lead levels; homes with low preremediation lead levels showed little or no benefit. Before remediation, homes located in areas with high soil lead levels or with "poor" dust proofing had higher lead levels than those in areas with lower soil lead levels or with "medium" or "good" dust proofing; these relative differences remained after remediation. There was no evidence that lead loading was reduced by an increased opportunity to become aware of lead issues. We conclude that remediation is an effective strategy for reducing the lead exposure of children living in homes with high indoor lead levels.

  17. The relationship between environmental lead and blood lead in children : a study in environmental epidemiology

    NARCIS (Netherlands)

    Brunekreef, B.

    1985-01-01

    This study deals with the relationship between environmental lead and blood lead in children.
    Chapter 1 provides a summary of the environmental health aspects of lead. The occurrence of lead in the environment and in man is described; children are discussed as a population at

  18. Evolution of protein-protein interactions

    Indian Academy of Sciences (India)

    Evolution of protein-protein interactions · Our interests in protein-protein interactions · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

  19. Lead, arsenic, and copper content of crops grown on lead arsenate-treated and untreated soils

    Energy Technology Data Exchange (ETDEWEB)

    Chisholm, D

    1972-01-01

    Increased lead and arsenic concentrations in the surface soil (0-15 cm), resulting from applications of lead arsenate (PbHAs0/sub 1/), increased both lead and arsenic levels in crops grown on treated plots. The lead levels in some crops approached or exceeded the Canadian residue tolerance of 2.0 ppM. Lead arsenate soil treatments did not affect copper absorption by crops. On areas such as old orchard land contaminated with lead arsenate residues it may be advisable to ascertain crops, and also to determine the lead affinity and arsenic sensitivity of the plants to be grown.

  20. Lead: Aspects of its ecology and environmental toxicity. [physiological effects of lead compound contamination of environment

    Science.gov (United States)

    Siegel, S. M.

    1973-01-01

    An analysis of lead toxicity in the Hawaiian environment was conducted. It was determined that lead enters the environment as an industrial contaminant resulting from the combustion of leaded gasoline. The amount of lead absorbed by the plants in various parts of the Hawaiian Islands is reported. The disposition of lead in the sediments of canals and yacht basins was investigated. The methods for conducting the surveys of lead content are described. Possible consequences of continued environmental pollution by burning leaded gasoline are discussed.