52,293 research outputs found
Studies on metals in motor neuron disease
No full textA slow but steady increase in neurodegenerative disorders has been noted in recent decades. Degenerations in the nervous system are found in Alzheimer's disease, Parkinson's disease and motor neuron diseases. Amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases. It is often considered a model disorder of neurodegeneration. Early symptoms of ALS are limb weakness or weakness in muscles of speech and swallowing. Muscle atrophy follow and a slowly progressing paralysis spreads to respiratory muscles invariably leading to death in respiratory failure. Neurophysiological investigations are necessary for proper diagnosis, and it is important to rule out treatable diagnostic alternatives such as myopathies or polyneuropathies.The cause of ALS is unknown. Prevailing theories include genetic, viral, inflammatory, oxidative or toxic mechanisms. Some indications point toward metallotoxic etiologies. Clusters of ALS have been observed in regions where geological conditions cause elevated metal concentrations in water and soil. Several studies show increased frequency of ALS in certain occupations. ALS-like conditions are found in animals, notably in horses, where metal exposure can be suspected. In addition animal metal exposure experiments show accumulations of metals in the spinal cord.The aim of this thesis project is to clarify the role of metals in ALS. The hypothesis tested is that neurotoxic metals contribute significantly to the pathogenesis of ALS. To study this we have measured concentrations of 22 metals in cerebrospinal fluid (CSF) and plasma from patients with ALS and from controls, and correlated findings to literature data to suggest a model for ALS pathogenesis.Increased concentrations were found for the metals manganese, aluminum, cadmium, cobalt, copper, zinc, lead, vanadium and uranium in CSF from patients with ALS compared to controls. Manganese showed the most prominent correlation. Simultaneous sampling from plasma did not show these elevated concentrations, indicating metal accumulations in ALS CSF. Most of the metals detected in CSF from ALS patients are neurotoxicants.Studies of mercury distribution in a monkey showed mercury accumulations in the spinal cord after respiratory exposure to mercury. Motor neurons of the spinal cord seem to be more vulnerable to metal toxicity then surrounding cells, as they lack protection from the metal-binding protein metallothionein. Patient exposure to metals, distribution by the bloodstream, penetration of protective barriers and direct toxic effects on neurons of the spinal cord is suggested to be causative in ALS.It is concluded that neurotoxic metals can reach and affect the anterior horn cells of motor neurons and thereby contribute to the pathogenesis of ALS.List of scientific papersI. Holmøy T., Bjørgo K., Roos Per M. Slowly progressing amyotrophic lateral sclerosis caused by H46R SOD1 mutation. European Neurology. Letter to the Editor. 2007. 490, 58: 57-58. https://doi.org/10.1159/000102170 II. Holmoy T, Roos Per M, Kvale O. Amyotrophic lateral sclerosis: cytokine profile of cerebrospinal fluid T cell clones. Amyotrophic lateral sclerosis and other motor neuron diseases. 2006.7:183-186. https://doi.org/10.1080/17482960600664730 III. Roos Per M., Dencker L. Mercury in the spinal cord after inhalation of mercury. Basic & Clinical Pharmacology & Toxicology. 2012. Aug;111(2):126-132. https://doi.org/10.1111/j.1742-7843.2012.00872.x IV. Gellein K., Roos Per M., Evje L., Vesterberg O., Flaten T. P., Nordberg M., Syversen T. Separation of proteins in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS. Brain Research. 2007. Oct;1174 (12):136-142. https://doi.org/10.1016/j.brainres.2007.08.004 V. Roos Per M., Lierhagen S., Flaten TP., Syversen T., Vesterberg O., Nordberg M. Manganese in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis. Experimental Biology and Medicine (Maywood). 2012 Jul 1,237(7):803-810. https://doi.org/10.1258/ebm.2012.011396 VI. Roos Per M., Vesterberg O., Syversen T., Flaten TP., Nordberg M. Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis. Biological Trace Element Research. 2013. Feb;151(2):159-170. https://doi.org/10.1007/s12011-012-9547-x </p
Replication Data for: The importance of foundation species identity: a field experiment with lichens and their associated micro-arthropod communities
No full textThis dataset contains reproduction data for "The importance of foundation species identity: a field experiment with lichens and their associated micro-arthropod communities" by Roos et al. 2022. The dataset contains data on microarthropod abundance extracted from lichen patches with different species compositions (from monocultures to four species in mixture).Foundation species provide habitat and modify the availability of resources to other species. In nature, multiple foundation species may occur in mixture, but little is known on how their interactions shape the community assembly of associated species. Lichens provide both structural habitat and resources to a variety of associated organisms and thereby serve as foundation species. In this study, we use mat-forming lichens and their associated micro-arthropods as a miniature ecosystem to study potential synergies between foundation species diversity and the abundance and functional diversity of higher trophic levels. We created lichen patches with monocultures and mixtures of up to four species, and extracted Collembola (identified to species level), Oribatida, Mesostigmata, Pseudoscorpiones, and Araneae with Tullgren apparatuses after 106 days of incubation within a natural lichen mat. We found that different lichen species supported different arthropod abundances. For 19 out of in total 55 lichen mixtures and arthropod groups, we found non-additive, synergistic effects on arthropod abundance, although the specific lichen mixture causing synergistic effects differed per arthropod group. In addition, synergistic effects on arthropod abundance were more common for arthropod groups at lower trophic levels. The functional diversity of lichen mixtures explained patterns in Collembola abundance, but in the opposite direction than hypothesized because synergistic responses were more frequent in functionally similar lichen mixtures. Finally, we found few effects of lichen mixture identity or diversity on the functional diversity of Collembola communities. When applied to large scale ecosystems, our results suggest that understanding interactions between coexisting foundation species and identifying those species that drive synergistic effects of foundation species on consumer biota, is likely to be of importance to biodiversity conservation and restoration efforts
Waardplantgeschiktheid van roos voor het wortelknobbelaaltje Meloidogyne hapla : zeven M. hapla-isolaten, zes cultivars en een onderstam
No full textHet noordelijk wortelknobbelaaltje, Meloidogyne hapla, wordt de laatste jaren steeds vaker aangetroffen in substraatteelten van roos. Onderzoek naar de schadelijkheid en populatieontwikkeling van dit wortelaaltje bij roos op substraat vereist de aanwezigheid van een vatbare cultivar of onderstam en een M. hapla-isolaat dat tot aantasting in staat is. Omdat uit het eerste onderzoek bleek dat niet elke roos en isolaat een geschikte combinatie is, is een potproef uitgevoerd om geschikte roos/isolaat-combinaties te vinden. In de proef zijn zes rozencultivars, Black Beauty, Indian Femma!, Queensday, Red Berlin, Sunbeam en Vendela en de onderstam Natal Briar opgenomen in combinatie met zeven verschillende M. hapla-isolaten: Has, Haw, Hbz, Hby, Hh, Hj en RZ. Alle isolaten zijn getest in een zilverzand/perliet grof-substraat (2 : 1). Alleen het isolaat RZ is ook in kokos en perliet fijn beproefd. De planten zijn geïnoculeerd met 10.000 J2 van M. hapla per plant en negen weken later beoordeeld op aantallen eimassa’s per plant. Het tomatenras Moneymaker diende als zeer vatbare controle om de vitaliteit van de isolaten te controleren. In tegenstelling tot het tomatenras Moneymaker, waarop gemiddeld over alle M. hapla-isolaten 638 eimassa’s per plant aanwezig waren, waren de rozen met gemiddeld bijna 8 eimassa’s per plant beduidend minder vatbaar voor de geteste M. hapla-isolaten. Van de rozen zijn de onderstam Natal Briar en de cultivar Vendela het meest vatbaar, wat met name geldt voor de isolaten Hbz en Hh. Deze roos/isolaat-combinaties leverden 43 tot 58 eimassa’s per plant op. In combinatie met de andere cultivars varieerde het aantal eimassa’s voor Hbz en Hh van 0,2 tot 23,8 per plant. De isolaten Has, Haw, Hby, Hj en RZ, leverden bij alle onderzochte rozen geen of slechts weinig eimassa’s op, variërend van 0 tot 15,5 eimassa’s per plant. Dit onderzoek heeft vier roos/isolaat-combinaties opgeleverd waarmee de schade- en bestrijdingsproeven kunnen worden uitgevoerd, namelijk Natal Briar en Vendela in combinatie met de isolaten Hbz en Hh
Waardplantgeschiktheid van roos voor het wortelknobbelaaltje Meloidogyne hapla : zeven M. hapla-isolaten, zes cultivars en een onderstam
No full textHet noordelijk wortelknobbelaaltje, Meloidogyne hapla, wordt de laatste jaren steeds vaker aangetroffen in substraatteelten van roos. Onderzoek naar de schadelijkheid en populatieontwikkeling van dit wortelaaltje bij roos op substraat vereist de aanwezigheid van een vatbare cultivar of onderstam en een M. hapla-isolaat dat tot aantasting in staat is. Omdat uit het eerste onderzoek bleek dat niet elke roos en isolaat een geschikte combinatie is, is een potproef uitgevoerd om geschikte roos/isolaat-combinaties te vinden. In de proef zijn zes rozencultivars, Black Beauty, Indian Femma!, Queensday, Red Berlin, Sunbeam en Vendela en de onderstam Natal Briar opgenomen in combinatie met zeven verschillende M. hapla-isolaten: Has, Haw, Hbz, Hby, Hh, Hj en RZ. Alle isolaten zijn getest in een zilverzand/perliet grof-substraat (2 : 1). Alleen het isolaat RZ is ook in kokos en perliet fijn beproefd. De planten zijn geïnoculeerd met 10.000 J2 van M. hapla per plant en negen weken later beoordeeld op aantallen eimassa’s per plant. Het tomatenras Moneymaker diende als zeer vatbare controle om de vitaliteit van de isolaten te controleren. In tegenstelling tot het tomatenras Moneymaker, waarop gemiddeld over alle M. hapla-isolaten 638 eimassa’s per plant aanwezig waren, waren de rozen met gemiddeld bijna 8 eimassa’s per plant beduidend minder vatbaar voor de geteste M. hapla-isolaten. Van de rozen zijn de onderstam Natal Briar en de cultivar Vendela het meest vatbaar, wat met name geldt voor de isolaten Hbz en Hh. Deze roos/isolaat-combinaties leverden 43 tot 58 eimassa’s per plant op. In combinatie met de andere cultivars varieerde het aantal eimassa’s voor Hbz en Hh van 0,2 tot 23,8 per plant. De isolaten Has, Haw, Hby, Hj en RZ, leverden bij alle onderzochte rozen geen of slechts weinig eimassa’s op, variërend van 0 tot 15,5 eimassa’s per plant. Dit onderzoek heeft vier roos/isolaat-combinaties opgeleverd waarmee de schade- en bestrijdingsproeven kunnen worden uitgevoerd, namelijk Natal Briar en Vendela in combinatie met de isolaten Hbz en Hh
His+ reversions Caused in Salmonella typhimurium by different types of ionizing radiation
No full textThe yield of his+ reversions in the Ames Salmonella tester strain TA2638 has been determined for 60Co γ rays, 140 kV X rays, 5.4 keV characteristic X rays, 2.2 MeV protons, 3.1 MeV α particles, and 18 MeV/U Fe ions. Inactivation studies were performed with the same radiations. For both mutation and inactivation, the maximum effectiveness per unit absorbed dose was obtained for the characteristic X rays, which have a dose averaged linear energy transfer (LET) of roughly 10 keV/μm. The ratio of the effectiveness of this radiation to γ rays was 2 for inactivation and about 1.4 for the his+ reversion. For both end points the effectiveness decreases substantially at high LET, i.e., for the α particles and the Fe ions. The composition of the bottom and the top agar was the one recommended by Maron and Ames [Mutat. Res. 113, 173-215 (1983)] for application in chemical mutagenicity tests. The experiments with the less penetrating radiations differed from the usual protocol by utilization of a technique of plating the bacteria on the surface of the top agar. As in an earlier study [Roos et al., Radiat. Res. 104, 102-108 (1985)] greatly enhanced yields of mutations, relative to the spontaneous reversion rate, were obtained in these experiments by performing the irradiations 6 h after plating, which differs from the conventional procedure to irradiate the bacteria shortly after plating
The adsorption of chymosin and lysozyme onto emulsion droplets and their association with casein
No full textThe proteolytic action of proteases present in cheese plays a major role in the ripening of cheese. These proteases originate from the rennet, the starter cultures and from the milk itself. The proteolysis in cheese results in the degradation of the casein proteins into smaller peptides and free amino acids, which act as flavour precursors. The ripening of cheese under conditioned storage is time consuming and costly. Addition of specific enzymes to the cheese milk is one of several options to accelerate ripening. A major problem then is that hardly any of these proteases end up in the cheese and most disappear with the whey stream. Entrapment of bacteria and milk fat globules into the casein matrix of the curd is due to their particle character. Immobilisation of proteases onto particles would thus result in retention of these proteins in the curd. Ideally, for reasons of acceptance, these particles should originate from the milk itself or at least be edible.In this study, in a more general approach, soya oil emulsion droplets and casein micelles, being protein aggregates, were tested as the carrier system. Chymosin and lysozyme were taken as the enzymes to be immobilized, because of their relevance to the dairy industry and because they are scientifically well-known. Moreover, their biochemical divergence make them suitable models for study.The literature provides several studies on adsorption of proteins onto interfaces. Few of these proteins are enzymes. In cases where lysozyme was studied, it was included because of its extraordinary properties as a protein and not because of its enzymatic activity. Apart from (phospho)lipases there is scarcely any literature that describes activity of enzymes adsorbed onto the oil/water or air/water interfaces. Proteins tend strongly to accumulate in interfaces and for that reason are said to be very surface active. This adsorption is accompanied by a conformational change of the three-dimensional structure of the protein that results in some unfolding, ranging from almost full stretching of the peptide chain to a more conserved conformation. Hydrophobic residues or patches of the protein, mostly buried inside the molecule, will tend to position themselves next to or even protrude partly into, the hydrophobic phase of an oil/water interface.The extent of conformational change depends on the conformational stability of the protein, which, in turn, depends on pH, temperature, ionic strength etc. Furthermore, the extent of unfolding will be dependent on the surface area available and on the time scale, and hence, on protein concentration. In a static condition, adsorption at the interface will be diffusion driven, whereas during emulsification the time of adsorption will be determined by convection and will be very much shorter. Consequently, conformational changes of proteins during emulsification should be smaller because full surface coverage may be reached before unfolding can occur. In the case of enzymes being adsorbed the emulsification process would therefore offer an opportunity to retain activity.The relation between the surface pressureΠi.e. the extent of surface tension decrease and the amount of protein adsorbed per unit surface area availableΓ, provides a possibility to relate the size of the adsorbed protein molecules, and thereby the extent of unfolding, to the surface load. As mentioned earlier the extent of unfolding should be less at a higherΓvalue. It has been calculated that lysozyme, an enzyme of high conformational stability, hardly unfolds at the air/water interface, even at low surface coverage. For the oil/water interface, however, a considerable increase in the radius of the protein molecules was observed at low surface load. At surface coverage of > 1.5 mg.m -2, the radius remained more or less constant, indicating that substantial unfolding did not occur. Despite this rigidity, the enzyme had lost all of its enzymatic activity in situ and it even remained inactive after desorption.Apparently, conformational changes in the enzyme molecule do not necessarily become manifest in a larger size for the molecule. Chymosin, being an enzyme of smaller conformational stability, naturally lost all of its activity due to adsorption onto the oil/water interface. In experiments with the enzymes coadsorbed simultaneously with bovine serum albumin, or the one after the other, there was no retention of in situ activity. Chymosin also proved to be inactivated at the expanding air/water interface due to air incorporation, if this occurred e.g. during homogenization.During the cheese-making process enzymes like chymosin and lysozyme are retained in the curd. This retention must be due to association of the enzymes with the casein from milk. In order to adsorb the enzymes with retention of activity, the various casein fractions were used to make and stabilize a soya-oil emulsion, and the enzyme was subsequently allowed to associate with the casein. The extent of association of lysozyme with the casein fractions was in the orderα s -casein >β-casein >κ-casein. Only for theκ-casein stabilized emulsion, was lysozyme association dependent on pH within the range of pH 5.2 - 6.4 (greater for a lower pH). Furthermore, the association with the caseins was not dependent on temperature, indicating that hydrophobic interactions were not predominant. The same trends were found with the various caseins in solution, albeit that association withκ-casein hardly occurred. It should be kept in mind that casein adsorbed at an interface will expose other amino acid residues compared to its behaviour when free in solution. For that reason the association behaviour in the two systems may differ.Because the association varies between caseins the extent of association with lysozyme depended on the composition of the casein micelles (aggregates of many casein molecules and calcium phosphate, as occurring especially in milk). As expected, casein micelles containing a higher proportion ofκ-casein associated less with lysozyme. It was found that lysozyme did not lose activity due to association with casein adsorbed on soya oil droplets or free in solution. However, lysozyme activity was markedly reduced when the enzyme was associated with casein micelles. In this system lysozyme also associated with casein in the interior of the casein micelle. The apparent loss of activity was most probably due to internal diffusion limitation. The difference of association for the various systems was also reflected in the free equilibrium concentration at which the surface excess plateau value was reached. In the system of adsorbed caseins this value was reached at a free lysozyme concentration of about 3 _M, whereas for the micellar system this value was about 100 times higher.The association of chymosin with casein has been studied in the same three systems of casein adsorbed onto soya-oil emulsion droplets, caseins in solution and caseins aggregated in casein micelles. It appears that chymosin only associated with adsorbedκ-casein and not with adsorbedαs- orβ-casein. Preceding the association, the caseinomacropeptide part ofκ-casein is split off, followed immediately by the aggregation of the soya-oil emulsion droplets containing the remaining para-κ-casein. This coagulation behaviour is identical to the renneting of milk during the cheese-making process. The association characteristics for chymosin are also comparable. The association was strongly dependent on pH and ionic strength, and on chymosin and casein concentration. Theκ-casein stabilized emulsion has proven to be a good model system for studying chymosin retention in curd. The chymosin associated with para-κ-casein was shown to be still active on addedκ-casein or on a fluorescent small hexapeptide substrate. Consequently, the active centre of the enzyme is presumably not involved in the association with casein.The association of chymosin with caseins free in solution has also been studied. Only in a solution containingκ-casein will addition of chymosin result in protein flocculation and precipitation. This flocculation is due to splitting off the caseino-macropeptide part ofκ-casein and the consecutive aggregation of the fairly hydrophobic and almost electrically neutral para-κ-casein molecules. The precipitated protein fraction also contains associated chymosin, to an extent depending on conditions like pH, ionic strength and casein and chymosin concentrations. In this system time and temperature also affected the extent of chymosin association. The association decreased with increased contact time and was stronger at higher temperatures.The protein content in the supernatant after centrifugation increased not only due to dissociation of chymosin but also due to the presence of casein fragments. Apparently, the dissociation of chymosin was related to its proteolytic action. The dissociation rate increased with decreasing pH where chymosin becomes more active and less specific. The dissociation also increased with temperature for a given time of contact. However, when extrapolated to a contact time of t = 0 (i.e. when dissociation due to proteolysis has not occurred yet) the association was observed to be somewhat stronger for a higher temperature. The effect of temperature on the proteolysis-dependent dissociation, apparently was stronger than its effect on the increase of the association. Since chymosin association depends on mutual association of caseins (see below), it will also depend on the temperature dependence of the latter. Dissociation of chymosin was not found in the system of caseins adsorbed onto emulsion droplets.The addition of small amounts ofαs- orβ-casein strongly decreased the extent of association of chymosin with para-κ-casein. This effect was stronger forαs-casein than forβ-casein. It was also found that the extent of chymosin association (moles of chymosin per mole of para-κ-casein) was larger when the system was diluted or, in other words, when the casein concentration was reduced. Both phenomena can be explained by assuming that competitive association occurs between the caseins and chymosin for interaction with a para-κ-casein molecule. Chymosin is only able to associate with a para-κ-casein molecule when that is not associated with other casein molecules. Thermodynamically speaking, the extent of association of chymosin is determined by the association constants that exist between all caseins under conditions as in the system. These association constants vary with pH, ionic strength, casein concentration and temperature.The model of competitive association is further developed and applied to the association of chymosin with casein micelles of various composition. It follows that chymosin will associate less with casein micelles composed ofαs- andκ-casein than with micelles composed ofβ- andκ-caseins. Again, this behaviour can be explained by competitive association, since different association constants exist for the caseins and chymosin for association with para-κ-casein. The relations for association and dissociation found in this casein micelle system are comparable with those found with caseins in solution. The kinetic model for competitive association is only a crude approximation. It does not provide possibilities of calculating all the association constants occurring in milk from the relations found from retention of chymosin in curd.</p
The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases
No full textImpaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of a-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. In this article we review available studies concerning Fe, Cu and Mn in Parkinson's disease and Wilson's disease. In Parkinson's disease local dysregulation of iron metabolism in the substantia nigra (SN) seems to be related to neurodegeneration with an increase in SN iron concentration, accompanied by decreased SN Cu and ceruloplasmin concentrations and increased free Cu concentrations and decreased ferroxidase activity in the cerebrospinal fluid. Available data in Wilson's disease suggest that substantial increases in CNS Cu concentrations persist for a long time during chelating treatment and that local accumulation of Fe in certain brain nuclei may occur during the course of the disease. Consequences for chelating treatment strategies are discussed. (C) 2014 Elsevier GmbH. All rights reserved
Gedualiseerde verhoudingen
No full textPer 7 maart 2002 is het dualistische model voor gemeentebestuur ingevoerd. Dit gebeurde naar aanleiding van het rapport-Elzinga: 'Dualisme en lokale democratie'. De staatscommissie-Elzinga heeft onderzocht welke verbeteringen in het functioneren van het gemeentebestuur aangebracht konden worden. Dualisering van het gemeentebestuur heeft onder andere veranderingen in de verhouding tussen topambtenaren en gemeenteraadsleden van de gemeente teweeggebracht. Het onderstaande artikel is een bewerking van het propedeusewerkstuk van student bestuurskunde Richard Roos waarin hij onderzoekt hoe die verhoudingen zijn veranderd
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