62 research outputs found

    Alterations in endocytic protein expression with increasing age in the transgenic APP695 V717I London mouse model of amyloid pathology: Implications for Alzheimer's disease

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    Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. A major risk factor for the development of Alzheimer's disease (AD) is increasing age, but the reason behind this association has not been identified. It is thought that the changes in endocytosis seen in AD patients are causal for this condition. Thus, we hypothesized that the increased risk of developing AD associated with ageing may be because of changes in endocytosis. We investigated using Western blotting whether the expression of endocytic proteins involved in clathrin-mediated and clathrin-independent endocytosis are altered by increasing age in a mouse model of amyloid pathology. We used mice transgenic for human amyloid precursor protein containing the V717I London mutation. We compared the London mutation mice with age-matched wild-type (WT) controls at three ages, 3, 9 and 18 months, representing different stages in the development of pathology in this model. Having verified that the London mutation mice overexpressed amyloid precursor protein and β-amyloid, we found that the expression of the smallest isoform of PICALM, a key protein involved in the regulation of clathrin-coated pit formation, was significantly increased in WT mice, but decreased in the London mutation mice with age. PICALM levels in WT 18-month mice and clathrin levels in WT 9-month mice were significantly higher than those in the London mutation mice of the same ages. The expression of caveolin-1, involved in clathrin-independent endocytosis, was significantly increased with age in all mice. Our results suggest that endocytic processes could be altered by the ageing process and such changes could partly explain the association between ageing and AD

    Selective reduction of APP-BACE1 activity improves memory via NMDA-NR2B receptor-mediated mechanisms in aged PDAPP mice

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    β-Amyloid (Aβ) accumulation is an early event of Alzheimer's disease (AD) pathogenesis. Inhibition of Aβ production by β-secretase (BACE) has been proposed as a potential therapeutic strategy for AD. However, BACE inhibitors lack specificity and have had limited clinical benefit. To better study the consequences of reducing BACE metabolism, specifically of APP, we used an antibody, 2B3, that binds to APP at the BACE cleavage site, inhibiting Aβ production. 2B3 was administered either directly into the lateral ventricles or by intraperitoneal injection to (platelet-derived growth factor promoter hAPP717V (PDAPP) mice and WT mice. 2B3 reduced soluble Aβ40 and βCTF (β-amyloid derived C-terminal fragment) and improved memory for object-in-place associations and working memory in a foraging task in PDAPP mice. 2B3 also normalized the phosphorylation of the N-methyl-D-aspartate receptor NR2B subunit and subsequent extracellular signal-regulated kinase signaling. The importance of this NR2B pathway for OiP memory was confirmed by administering the NR2B antagonist, Ro25-6981, to 18-month-old WT. In contrast, 2B3 impaired associative recognition memory in young WT mice. These data provide novel insights into the mechanism by which selective modulation of APP metabolism by BACE influences synaptic and cognitive processes in both normal mice and aged APP transgenic mice

    Planting material of enset (Ensete ventricosum), a key food security crop in southwest Ethiopia, is a key element in the dissemination of plant-parasitic nematode infection

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    Open Access Journal; Published online: 09 Jul 2021Enset (Ensete ventricosum), is a perennial herbaceous plant belonging to the family Musaceae, along with banana and plantain. Despite wild populations occurring in eastern, central and southern Africa, it is only in Ethiopia that the crop has been domesticated, where it is culturally and agriculturally symbolic as a food security crop. Although an under-researched orphan crop, enset serves as a staple food for about 20% of the Ethiopian population, comprising more than 20 million people, demonstrating its value in the country. Similar to banana and plantain, enset is heavily affected by plant-parasitic nematodes, with recent studies indicating record levels of infection by the root lesion nematode Pratylenchus goodeyi. Enset is propagated vegetatively using suckers that are purposely initiated from the mother corm. However, while banana and plantain suckers have proven to be a key source of nematode infection and spread, knowledge on the infection levels and role of enset suckers in nematode dissemination is lacking. Given the high levels of plant-parasitic nematodes reported in previous surveys, it is therefore speculated that planting material may act as a key source of nematode dissemination. To address this lack of information, we assessed enset planting material in four key enset growing zones in Ethiopia. A total of 340 enset sucker samples were collected from farmers and markets and analyzed for the presence of nematodes. Nematodes were extracted using a modified Baermann method over a period of 48 h. The root lesion nematode P. goodeyi was present in 100% of the samples, at various levels of infection. These conclusive results show that planting material is indeed a key source of nematode infection in enset, hence measures taken to ensure clean suckers for planting will certainly mitigate nematode infection and spread. The effect of nematode infection on yield and quality on enset remains to be investigated and would be a way forward to complement the nematode/disease studies conducted so far and add valuable knowledge to the current poorly known impact of pests and diseases

    The Ethiopian staple food crop enset (Ensete ventricosum) assessed for the first time for resistance against the root-lesion nematode Pratylenchus goodeyi

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    Open Access Article; Published online: 08 Feb 2021Pratylenchus goodeyi appears to be the most prevalent nematode pest of enset in Ethiopia, where it can occur in extremely high densities. However, the damage to yield or how different enset cultivars react to the nematode has yet to be determined. The current study therefore sought to establish a first assessment of these reactions by enset to P. goodeyi infection. Determining pest-resistant cultivars is an important task in developing management strategies. Our study evaluated nine enset cultivars to establish host response and identify potential sources of resistance. In addition, the pathogenicity of P. goodeyi was assessed on three enset cultivars. After 9 months’ growth, significant differences in final population densities (Pf) and reproduction factor (RF) were observed amongst the nine cultivars, with ‘Gefetanuwa’ the most susceptible (Pf = 25 799 and RF = 12.9), and similarly in a repeat experiment for 4.5 months (Pf = 126 534 and RF = 63.3). ‘Maziya’ and ‘Heila’ were the most resistant in the first experiment (Pf < 455 and RF < 0.2) as well as in the repeat, together with ‘Kellisa’ (Pf < 5255 and RF < 2.6). In the pathogenicity experiment four inoculum densities significantly affected the Pf and RF but not among the three cultivars ‘Maziya’, ‘Arkiya’ and ‘Heila’. This is the first known study to assess genotype reaction to P. goodeyi, which shows that there are significant differences in the reactions of different cultivars and that resistance appears to be present in enset

    Influencia de la radiación UV-B, sobre la biosíntesis de antocianinas en frutos de manzana (Malus domestica Borkh) CV.”ANNA” para condiciones de trópico alto en Boyacá Colombia

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    1 recurso en línea (73 páginas) : figuras, tablas.En la manzana roja, la coloración de la piel y las características fisicoquímicas, son factores importantes que determinan la calidad de los frutos; estos parámetros tienen un control de orden genético pero influenciado por condiciones ambientales en etapa de maduración de frutos. El color rojo está ligado a la biosíntesis de antocianinas, que son un grupo de pigmentos de color rojo, hidrosolubles, producto del metabolismo secundario mediado por luz UV, Y ampliamente distribuidos en el reino vegetal. En el presente estudio se determinó el IUV, se cuantifico antocianinas totales y se analizaron SST en frutos maduros de manzana cv “ANNA” cultivados en diferentes altitudes en localidades de Boyacá: Soracá a 2820 m.s.n.m, Tuta a 2640m.s.n.m y Nuevo Colon a 2450 m.s.n.m. Los resultados mostraron que en la localidad a mayor altitud (Soracá), el valor promedio del IUV fue mayor (14.9) y la acumulación de antocianinas totales igualmente fue el más alto (25.4 mg/100g). Se ha encontrado una correlaciòn positiva entre la intensidad de la radiación UV, altitud y concentración de antocianinas totales, mientras que para los SST no se encontraron diferencias significativas.Bibliografía y webgrafía: páginas 61-70MaestríaMagíster en Ciencias Biológica

    Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation

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    Contains fulltext : 169681.pdf (publisher's version ) (Open Access)Heterozygous mutations or deletions of the human Euchromatin Histone Methyltransferase 1 (EHMT1) gene are the main causes of Kleefstra syndrome, a neurodevelopmental disorder that is characterized by impaired memory, autistic features and mostly severe intellectual disability. Previously, Ehmt1+/- heterozygous knockout mice were found to exhibit cranial abnormalities and decreased sociability, phenotypes similar to those observed in Kleefstra syndrome patients. In addition, Ehmt1+/- knockout mice were impaired at fear extinction and novel- and spatial object recognition. In this study, Ehmt1+/- and wild-type mice were tested on several cognitive tests in a touchscreen-equipped operant chamber to further investigate the nature of learning and memory changes. Performance of Ehmt1+/- mice in the Visual Discrimination &Reversal learning, object-location Paired-Associates learning- and Extinction learning tasks was found to be unimpaired. Remarkably, Ehmt1+/- mice showed enhanced performance on the Location Discrimination test of pattern separation. In line with improved Location Discrimination ability, an increase in BrdU-labelled cells in the subgranular zone of the dentate gyrus was observed. In conclusion, reduced levels of EHMT1 protein in Ehmt1+/- mice does not result in general learning deficits in a touchscreen-based battery, but leads to increased adult cell proliferation in the hippocampus and enhanced pattern separation ability

    The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

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    RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

    Undersøkelser i Drammensfjorden 1982-84. Delrapport: Høyere vegetasjon

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    Undersøkelse av høyere vegetasjon i Drammensfjorden har i det vesentlige vist moderat næringsrike forhold. Tilfeller av moderat overgjødsling er observert på enkelte lokaliteter innerst i fjorden (Solumstranda, Gullaugbukta, Lahellbukta). Plantenes dybdeutbredelse er noe begrenset av dårlige lysforhold og nedslamming ved elvemunningene og innerst i fjorden, mest pga naturlig leirtransport. Forøvrig er forurensningseffekter ikke påvist. Vasspest er ikke observert, men det er flere potensielle voksesteder i den nordlige del av fjorden. Flere lokaliteter i indre område er vurdert som verneverdig

    Undersøkelser i Drammensfjorden 1982-84. Delrapport: Høyere vegetasjon

    No full text
    Undersøkelse av høyere vegetasjon i Drammensfjorden har i det vesentlige vist moderat næringsrike forhold. Tilfeller av moderat overgjødsling er observert på enkelte lokaliteter innerst i fjorden (Solumstranda, Gullaugbukta, Lahellbukta). Plantenes dybdeutbredelse er noe begrenset av dårlige lysforhold og nedslamming ved elvemunningene og innerst i fjorden, mest pga naturlig leirtransport. Forøvrig er forurensningseffekter ikke påvist. Vasspest er ikke observert, men det er flere potensielle voksesteder i den nordlige del av fjorden. Flere lokaliteter i indre område er vurdert som verneverdigeStatens forurensningstilsyn (SFT
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