| 51. |
- Darudi, Ahmad, et al.
(författare)
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The Robotic Earthshine Telescope
- 2010
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Ingår i: Proceedings of the SPIE. - : SPIE. - 1996-756X .- 0277-786X. ; 7733, s. 8-77332
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Konferensbidrag (refereegranskat)abstract
- Lund Observatory is presently designing and constructing a robotic telescope dedicated to studies of the Earth's albedo by measuring the ratio between the intensity of the dark and bright sides of the Moon. The telescope will operate both in broadband and narrow-band modes over the entire visible wavelength range and will transmit observational results back to the operation team over the Internet. Design challenges, in particular related to choice of CCD and stray light suppression, are described, together with the design of the optics, control system, and enclosure. Finally we present results from laboratory tests. The telescope will go into operation in the first half of 2011.
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| 52. |
- Diekstra, Frank P., et al.
(författare)
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UNC13A is a modifier of survival in amyotrophic lateral sclerosis
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:3, s. 630.e3-630.e8
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Tidskriftsartikel (refereegranskat)abstract
- A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive. We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. (C) 2012 Elsevier Inc. All rights reserved.
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| 53. |
- Dinasquet, Julie, et al.
(författare)
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Cascading effects of the ctenophore Mnemiopsis leidyi on the planktonic food web in a nutrient-limited estuarine system
- 2012
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Ingår i: Marine Ecology Progress Serie. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 460, s. 49-61
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Tidskriftsartikel (refereegranskat)abstract
- Increasing biomasses of gelatinous zooplankton presumably have major implications for the structure and function of marine food webs at large; however, current data on lower trophic levels are scarce, as most studies have focused on the immediate effects on zooplankton and fish larvae only. We examined the short-term impact of larvae and adults of the invasive ctenophore Mnemiopsis leidyi on a summer planktonic food web in the estuarine southern Baltic Sea, with special emphasis on the microbial loop. Grazing by M. leidyi reduced the mesozooplankton biomass, followed by increased dinoflagellate biomass in treatments with M. leidyi. While chlorophyll a increased most in the treatments with M. leidyi, small phytoplankton and ciliates decreased in all treatments. M. leidyi had a slight effect on bacterial abundance, but not on bacterial production, ectoenzymatic activities, or community composition. Undetectable levels of phosphate and a gradual accumulation of dissolved organic carbon during the experiment suggested a malfunctioning microbial loop scenario. The experiment shows that direct and indirect short-term effects of M. leidyi on the estuarine food web are limited to higher trophic levels and indicates that top-down and bottom-up consequences of M. leidyi expansions on the microbial loop will likely depend on local nutrient conditions.
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| 54. |
- Fanos, Joanna H, et al.
(författare)
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Impact of presymptomatic genetic testing for familial amyotrophic lateral sclerosis
- 2011
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 13:4, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The Pre-familial Amyotrophic Lateral Sclerosis (Pre-fALS) study is a longitudinal study of individuals potentially at risk for developing familial amyotrophic lateral sclerosis. Our goals were to (1) explore participants' decisions of whether to learn results of presymptomatic testing or not; (2) understand the psychosocial impact of these decisions; and (3) assess preferences for receiving results by telephone or in person.METHODS: The sample for this substudy comprised 20 participants drawn randomly from autosomal dominant mutant superoxide dismutase 1 families in the Pre-fALS study. Twenty participants completed a semistructured phone interview; prominent themes were identified and rated.RESULTS: Fourteen participants chose to learn results; six had mutant superoxide dismutase 1 and eight had wild-type superoxide dismutase 1. Of the six who initially elected nondisclosure, three were reconsidering their decision. Regardless of the results and method of counseling, participants had adapted well, at least in the short term.CONCLUSION: We recommend that (1) those considering presymptomatic genetic testing should undergo professional counseling to help decide whether to learn results; (2) discussion should include the option of telephone genetic counseling for those without easy access to in-person counseling; and (3) those who initially decline to learn results should be offered the opportunity to learn their mutation status as their decision evolves.
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| 55. |
- Forsberg, Karin, et al.
(författare)
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Glial nuclear aggregates of superoxide dismutase-1 are regularly present in patients with amyotrophic lateral sclerosis
- 2011
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Ingår i: Acta Neuropathologica. - : SpringerLink. - 0001-6322 .- 1432-0533. ; 121:5, s. 623-634
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Tidskriftsartikel (refereegranskat)abstract
- The most common cause of amyotrophic lateral sclerosis (ALS) is mutations in superoxide dismutase-1 (SOD1). Since there is evidence for the involvement of non-neuronal cells in ALS we searched for signs of SOD1 abnormalities focusing on glia. Spinal cords from 9 ALS patients carrying SOD1 mutations, 51 patients with sporadic or familial ALS who lacked such mutations, and 46 controls were examined by immunohistochemistry. A set of anti-peptide antibodies with specificity for misfolded SOD1 species was used. Misfolded SOD1 in the form of granular aggregates was regularly detected in the nuclei of ventral horn astrocytes, microglia and oligodendrocytes in ALS patients carrying and as well as lacking SOD1 mutations. There was negligible staining in neurodegenerative and non-neurological controls. Misfolded SOD1 appeared occasionally also in nuclei of motoneurons of ALS patients. The results suggest that misfolded SOD1 present in glial and motoneuron nuclei may generally be involved in ALS pathogenesis.
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| 56. |
- Forsberg, Karin, et al.
(författare)
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Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients
- 2010
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 5:7, s. e11552-
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.
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| 57. |
- Freischmidt, Axel, et al.
(författare)
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Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
- 2014
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 137:11, s. 2938-2950
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
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| 58. |
- Gallo, Valentina, et al.
(författare)
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Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort.
- 2013
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 80:9, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. METHODS: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. RESULTS: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056). CONCLUSION: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.
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| 59. |
- Ganesalingam, Jeban, et al.
(författare)
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pNfH is a promising biomarker for ALS
- 2013
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Ingår i: Amytrophic Lateral Sclerosis and Frontotemporal degeneration. - : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 14:2, s. 146-149
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Tidskriftsartikel (refereegranskat)abstract
- A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median n = 2787 pg/ml, n = 150), compared to headache and other benign controls (3 (4 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (27 (pg/ml for n = 20) which was also highly significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2) = 0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.
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| 60. |
- Graffmo, Karin S., et al.
(författare)
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Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:1, s. 51-60
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Tidskriftsartikel (refereegranskat)abstract
- A common cause of amyotrophic lateral sclerosis (ALS) is mutations in the gene encoding superoxide dismutase-1. There is evolving circumstantial evidence that the wild-type protein can also be neurotoxic and that it may more generally be involved in the pathogenesis of ALS. To test this proposition more directly, we generated mice that express wild-type human superoxide dismutase-1 at a rate close to that of mutant superoxide dismutase-1 in the commonly studied G93A transgenic model. These mice developed an ALS-like syndrome and became terminally ill after around 370 days. The loss of spinal ventral neurons was similar to that in the G93A and other mutant superoxide dismutase-1 models, and large amounts of aggregated superoxide dismutase-1 were found in spinal cords, but also in the brain. The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.
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