59 research outputs found
NR4A orphan nuclear receptors in immediate early regulation of retinoid signaling and neuroprotection
No full textNR4A receptors show distinct properties that make them unique within the family of nuclear receptors. They lack a ligand-binding cavity and a canonical coactivator-binding site and they are induced both in vivo and in vitro in an immediate early way by an extremely wide repertoire of substances/conditions. Apart from their specific roles during development, they play crucial, yet not fully charazterized, roles in sensing of and responding to changes in the cellular environment.In paper I, we provide novel insights into the mechanism of NR4A-mediated transcription by identifying an alternative coactivator-binding surface that is unique to the NR4A family of nuclear receptors. We also report a link between NR4A transcriptional activity and protein turnover and identify protein sequence differences between the NR4A receptor members that may account for their differential transcriptional activity.In paper II, we provide evidence suggesting that NR4A receptors can influence signaling events of other nuclear receptors via inducing the expression of fatty acid binding protein 5. Specifically, NR4A receptors can enhance retinoic acid-induced signaling of the peroxisome proliferator-activated receptor and docosahexaenoic acid-induced activation of the retinoid X receptor.In paper III, we demonstrate that NR4A proteins are induced by cyclic AMP response element binding protein (CREB) in neurons exposed to excitotoxic and oxidative insults and that they function as mediators of CREB-induced neuronal survival by inducing the expression of a battery of neuroprotective genes. Moreover, we show that mice with null mutations in three out of six NR4A alleles show increased oxidative damage, blunted induction of neuroprotective genes and increased vulnerability in the hippocampus after treatment with the excitotoxin kainic acid.In summary, we show that NR4A receptors utilize a distinct surface to bind coactivators, that they can influence signaling by two other nuclear receptors by upregulating a fatty acid binding protein and that they are essential mediators of neuroprotection after exposure to neuropathological stress.List of scientific papersI. Volakakis N, Malewicz M, Kadkhodai B, Perlmann T, Benoit G (2006). "Characterization of the Nurr1 ligand-binding domain co-activator interaction surface." J Mol Endocrinol. 37(2): 317-26. https://pubmed.ncbi.nlm.nih.gov/17032747II. Volakakis N, Joodmardi E, Perlmann T (2009). "NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5." Biochem Biophys Res Commun. 390(4): 1186-91. https://pubmed.ncbi.nlm.nih.gov/19861119III. Volakakis N, Kadkhodaei B, Joodmardi E, Wallis K, Panman L, Silvaggi J, Spiegelman BM, Perlmann T (2010). "NR4A orphan nuclear receptors trigger a neurorotective pathway induced by elevatated cyclic AMP." [Submitted]</p
Composition comparée des produits végétaux 'Bio' et issus de l'agriculture conventionnelle: l'étude conduite par l'Université de Newcastle
No full textVoir la publication: Baranski, M., Srednicka-Tober, D., Volakakis, N., Seal, C., Sanderson, R., Stewart, G. B., Benbrook, C., Biavati, B., Markellou, E., Giotis, C., Gromadzka-Ostrowska, J., Rembialkowska, E., Skwarlo-Sonta, K., Tahvonen, R., Janovska, D., Niggli, U., Nicot, P., Leifert, C. (Auteur de correspondance) (2014). Higher antioxidant concentrations, and less cadmium and pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition, fisrt view. DOI : 10.1017/S0007114514001366 http://prodinra.inra.fr/record/259178Voir la publication:Baranski, M., Srednicka-Tober, D., Volakakis, N., Seal, C., Sanderson, R., Stewart, G. B., Benbrook, C., Biavati, B., Markellou, E., Giotis, C., Gromadzka-Ostrowska, J., Rembialkowska, E., Skwarlo-Sonta, K., Tahvonen, R., Janovska, D., Niggli, U., Nicot, P., Leifert, C. (Auteur de correspondance) (2014). Higher antioxidant concentrations, and less cadmium and pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition, fisrt view. DOI : 10.1017/S0007114514001366http://prodinra.inra.fr/record/259178absen
Composition comparée des produits végétaux 'Bio' et issus de l'agriculture conventionnelle: l'étude conduite par l'Université de Newcastle
No full textVoir la publication:Baranski, M., Srednicka-Tober, D., Volakakis, N., Seal, C., Sanderson, R., Stewart, G. B., Benbrook, C., Biavati, B., Markellou, E., Giotis, C., Gromadzka-Ostrowska, J., Rembialkowska, E., Skwarlo-Sonta, K., Tahvonen, R., Janovska, D., Niggli, U., Nicot, P., Leifert, C. (Auteur de correspondance) (2014). Higher antioxidant concentrations, and less cadmium and pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition, fisrt view. DOI : 10.1017/S0007114514001366http://prodinra.inra.fr/record/259178absen
Author Correction: Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease (Nature Communications, (2020), 11, 1, (2434), 10.1038/s41467-020-16225-5)
No full textThe original version of this Article contained an error in the Acknowledgments, which incorrectly read “The research leading to these results has received funding from the New York Stem Cell Foundation (to M.P.), the European Research Council (ERC Grant Agreement no. 30971, to M.P.), the Swedish Research Council [grant agreements 521-2012-5624 (to M.P.), 2016-02506 (to T.P.) and 70862601/Bagadilico)], Swedish Parkinson Foundation (Parkinsonfonden, to M.P.), Swedish Brain Foundation (Hjärnfonden, to M.P.), the Strategic Research Area at Lund University Multipark (Multidisciplinary research in Parkinson’s disease), StratRegen grant Karolinska Institutet (to T.P.); Knut and Alice Wallenberg Foundation (to T.P.), Söderbergs Stiftelse (to T.P.) and Svenska Sällskapet för Medicinsk Forskning (to K.T.). M.P. is a New York Stem Cell Foundation—Robertson Investigator.’ The correct version states ‘ERC Grant Agreement no. 771427, to M.P.’ in place of ‘ERC Grant Agreement no. 30971, to M.P.’ This has been corrected in both the PDF and HTML versions of the Article
The effect of organic and conventional management on the yield and quality of wheat grown in a long-term field trial
No full textThe performance of winter wheat was evaluated under organic (ORG) and conventional (CON) management systems in the Nafferton Factorial Systems Comparison (NFSC) long-term field trial. The present study separates out the crop protection and fertility management components of organic and conventional production systems using two levels each of crop protection (CP) and fertility management (FM). The experimental design provided the four combinations of crop protection and fertility (CON-CP CONFM, CON-CP ORG-FM, ORG-CP CON-FM and ORG-CP ORG-FM) to evaluate their effects on yield, quality (protein content and hectolitre weight) and disease levels during the period 2004–2008. The conventional management system (CON-CP CON-FM) out-yielded the organic management system (ORG-CP ORG-FM) in all years by an average of 3.1 t ha−1, i.e. 7.9 t ha−1 vs. 4.8 t ha−1. Fertility management was the key factor identified limiting both yield and grain protein content in the ORG management system. The CON-FM produced on average a 3% higher protein content than ORG-FM in all years (12.5% vs. 9.7%). However the ORG-CP system produced higher protein levels than CON-CP although it was only in 2008 that this was statistically significant. In contrast to protein content it was ORG-FM which produced a higher hectolitre weight than the CON-FM system (71.6 kg hl−1 vs. 71.0 kg hl−1). The clear and significant differences in yield and protein content between the ORG-FM and CON-FM systems suggest a limited supply of available N in the organic fertility management system which is also supported by the significant interaction effect of the preceding crop on protein content. The pRDA showed that although fertilisation had the greatest effect on yield, quality and disease there was also a considerable effect of crop protection and the environment
Transcription factor control in neuronal maintenance and survival
No full textThe Transcription factor (TF) Nurr1 is essential for the development of a group of dopamine neurons that are located in the ventral midbrain (also referred to as mesencephalon). A progressive pathology of these midbrain dopamine (mDA) neurons is evident in Parkinson s disease, the most frequent neurodegenerative movement disorder. In addition Nurr1 is expressed in a number of other CNS areas. In the hippocampus, Nurr1 is co-expressed with its homologues Nur77 and Nor1, collectively named for NR4A TF s. These TF s are rapidly and strongly induced in response to stressful stimuli and an acute NR4A induction has been noted in e. g. hippocampal, cortical and striatal neurons after ischemia, seizures and focal brain injury in rodents. However, the functional roles of the stress-induced NR4A-expression have remained unknown. As Nurr1 is critical for the mDA neuron development and is widely expressed in the adult CNS, we hypothesized that Nurr1 might also play a crucial role in maintaining mature neurons. To address this hypothesis, the functional consequences of gain-of-function or loss-of-function of NR4A proteins were assessed in maturing and adult neurons in vitro and in vivo. The research presented in paper I & II describes the consequences of spatiotemporal ablation of Nurr1 in mDA neurons in mice. Our results revealed that Nurr1 continues to be critical for the maturing mDA neurons and for maintaining a DA phenotype in the mDA neurons of adult mice. In paper III, the function of stress-induced NR4A proteins was characterized in vitro in cultured neurons and in vivo in the hippocampi of mice. The data revealed that stress-induced NR4A promoted neuroprotection in neurons, presumably by up-regulating a subset of neuroprotective genes. The work in paper IV deals with the mechanism by which Nurr1 mediates transcriptional activation. We identified a novel putative Nurr1 coregulator-binding site that might recruit as yet unknown coregulators.List of scientific papersI. Kadkhodaei B, Ito T, Joodmardi E, Mattsson B, Rouillard C, Carta M, Muramatsu S, Sumi-Ichinose C, Nomura T, Metzger D, Chambon P, Lindqvist E, Larsson NG, Olson L, Björklund A, Ichinose H, Perlmann T (2009). "Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons." J Neurosci. 29(50):15923-32. https://pubmed.ncbi.nlm.nih.gov/20016108II. Kadkhodaei B, Perlmann T (2010). "Maintenance of midbrain dopaminergic neurons." [Manuscript]III. Volakakis N, Kadkhodaei B, Joodmardi E, Wallis K, Vennström B, Spiegelman BM, Perlmann T (2010). "NR4A orphan nuclear receptors trigger a neuroprotective pathway induced by elevated cyclic AMP." [Manuscript]IV. Volakakis N, Malewicz M, Kadkhodai B, Perlmann T, Benoit G (2006). "Characterization of the Nurr1 ligand-binding domain co-activator interaction surface." J Mol Endocrinol. 37(2): 317-26. https://pubmed.ncbi.nlm.nih.gov/17032747</p
Altered Lipidomic Profile of Atheroprotective and Atherogenic Serum Lipoproteins in Patients With Peripheral Artery Disease
No full textShould we recommend organic crop foods on the basis of health benefits? Letter to the editor regarding the article by Baranski et al
No full textMulet Salort, JM. (2014). Should we recommend organic crop foods on the basis of health benefits? Letter to the editor regarding the article by Baranski et al. British Journal of Nutrition. 112(10):1745-1747. doi:10.1017/S0007114514002645S1745174711210Bradbury, K. E., Balkwill, A., Spencer, E. A., Roddam, A. W., Reeves, G. K., … Pirie, K. (2014). Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom. British Journal of Cancer, 110(9), 2321-2326. doi:10.1038/bjc.2014.148Dangour A , Aikenhead A & Hayter A , et al. (2009) Comparison of putative health effects of organically and conventionally produced foodstuffs: a systematic review. http://multimedia.food.gov.uk/multimedia/pdfs/organicreviewreport.pdf.Dangour, A. D., Dodhia, S. K., Hayter, A., Allen, E., Lock, K., & Uauy, R. (2009). Nutritional quality of organic foods: a systematic review. The American Journal of Clinical Nutrition, 90(3), 680-685. doi:10.3945/ajcn.2009.28041Barański, M., Średnicka-Tober, D., Volakakis, N., Seal, C., Sanderson, R., Stewart, G. B., … Leifert, C. (2014). Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition, 112(5), 794-811. doi:10.1017/s0007114514001366Tuomisto, H. L., Hodge, I. D., Riordan, P., & Macdonald, D. W. (2012). Does organic farming reduce environmental impacts? – A meta-analysis of European research. Journal of Environmental Management, 112, 309-320. doi:10.1016/j.jenvman.2012.08.018Gutteridge, J. M. C., & Halliwell, B. (2010). Antioxidants: Molecules, medicines, and myths. Biochemical and Biophysical Research Communications, 393(4), 561-564. doi:10.1016/j.bbrc.2010.02.071Seufert, V., Ramankutty, N., & Foley, J. A. (2012). Comparing the yields of organic and conventional agriculture. Nature, 485(7397), 229-232. doi:10.1038/nature11069Chandel, N. S., & Tuveson, D. A. (2014). The Promise and Perils of Antioxidants for Cancer Patients. New England Journal of Medicine, 371(2), 177-178. doi:10.1056/nejmcibr1405701Norwegian Scientific Committee for Food Safety Comparison of organic and conventional food and food production (2014) http://www.english.vkm.no/eway/default.aspx?pid = 278&trg = Content_6575&Main_6359 = 6575:0:31,2558&Content_6575 = 6393:1949052::0:6464:1:::0:0.United States Department of Agriculture (2010) Oxygen Radical Absorbance Capacity (ORAC) of selected foods, release 2. http://www.ars.usda.gov/services/docs.htm?docid = 15866.Ingenbleek, Y., & McCully, K. S. (2012). Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition, 28(2), 148-153. doi:10.1016/j.nut.2011.04.009Organización de Consumidores y Usuarios (2012) Alimentos Ecológicos, naturalmente nos dan la razón (Organic food, we were naturally right). http://www.ocu.org/alimentacion/alimentos/noticias/alimentos-ecologicos-naturalmente-nos-dan-la-razon.Guéguen, L., & Pascal, G. (2010). Le point sur la valeur nutritionnelle et sanitaire des aliments issus de l’agriculture biologique. Cahiers de Nutrition et de Diététique, 45(3), 130-143. doi:10.1016/j.cnd.2010.02.002Bast, A., & Haenen, G. R. M. M. (2013). Ten misconceptions about antioxidants. Trends in Pharmacological Sciences, 34(8), 430-436. doi:10.1016/j.tips.2013.05.010Benbrook C , Zhao X & Davies N , et al. (2008) New evidence confirms the nutritional superiority of plant-based organic foods. http://organiccenter.org/reportfiles/NutrientContentReport.pdf (accessed June 2014).Curl, C. L., Fenske, R. A., & Elgethun, K. (2003). Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Environmental Health Perspectives, 111(3), 377-382. doi:10.1289/ehp.5754Smith-Spangler, C., Brandeau, M. L., Hunter, G. E., Bavinger, J. C., Pearson, M., Eschbach, P. J., … Bravata, D. M. (2012). Are Organic Foods Safer or Healthier Than Conventional Alternatives? Annals of Internal Medicine, 157(5), 348. doi:10.7326/0003-4819-157-5-201209040-00007Del Rio, D., Rodriguez-Mateos, A., Spencer, J. P. E., Tognolini, M., Borges, G., & Crozier, A. (2013). Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases. Antioxidants & Redox Signaling, 18(14), 1818-1892. doi:10.1089/ars.2012.458
Gastrointestinal stromal tumors (GISTs) and synchronous intra-abdominal malignancies: Case series of a single institution’s experience
No full textBackground: Gastrointestinal stromal tumors (GISTs) quite often co-exist with other primary tumors, as seen in up to 33% of cases. In the literature such occurrences have primarily been described through case reports and rarely through case series, which is not sufficient to prove if there is an association between these two entities. Materials and Methods: We conducted a retrospective study using medical and pathological records from sixty-nine patients who underwent surgical treatment for GIST in a single university surgical department between 2011 and 2019. Seven cases of GIST accompanying a synchronous primary tumor were identified and included in the study. Results: Survival analysis comparing the overall survival of patients with single GIST versus patients with concurrent GIST and another primary tumor, has shown no statistically significant difference between these two groups (p = 0.19). However, when comparing the recurrence rate, patients with synchronous GISTs and another primary tumor have a statistically significant increased possibility for recurrence (p = 0.02). Statistical analysis comparing the size of GISTs between the two groups has shown that patients with single GIST have larger tumors than patients with synchronous tumors (p = 0.048). Conclusions: The synchronous occurrence of GISTs and other intra-abdominal tumors is more common than previously considered, though it is not yet clear if there is a causal association for the concomitant occurrence. Further studies are required to elucidate the genetic and molecular mechanisms of carcinogenesis and progression associating GIST and synchronous tumors. Copyright: © 2020 Diamantis et al
Effect of Climate, Crop Protection, and Fertilization on Disease Severity, Growth, and Grain Yield Parameters of Faba Beans (<em>Vicia faba</em> L.) in Northern Britain: Results from the Long-Term NFSC Trials
No full text\ua9 2024 by the authors. Faba beans are one of the most suitable grain legume crop for colder, maritime climates. However, there is limited information on the effect of changing from conventional to organic production methods and potential impacts of global warming on the health and performance of faba bean crops in Northern Europe. We therefore assessed the performance of faba beans grown with contrasting crop protection (with and without pesticides) and fertilization (with and without P and K fertilizer input) regimes used in organic and conventional production in seven growing seasons. Conventional crop protection and fertilization regimes had no effect on foliar disease severity, but resulted in small, but significant increases in faba bean yields. The overall yield gap between organic and conventional production regimes was relatively small (~10%), but there was substantial variation in yields between growing seasons/years. Redundancy analysis (RDA) showed that climate explanatory variables/drivers explained the largest proportion of the variation in crop performance and identified strong positive associations between (i) temperature and both straw and grain yield and (ii) precipitation and foliar disease severity. However, RDA also identified crop protection and variety as significant explanatory variables for faba bean performance. The relatively small effect of using P and K fertilizers on yields and the lack of a measurable effect of fungicide applications on foliar disease severity indicate that the use of these inputs in conventional faba beans may not be economical. Results also suggest that the yield gap between organic and conventional faba bean production is significant, but smaller than for other field crops
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