Dataset Information

Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila.

ABSTRACT: The view that only the production and deposition of Abeta plays a decisive role in Alzheimer's disease has been challenged by recent evidence from different model systems, which attribute numerous functions to the amyloid precursor protein (APP). To investigate the potential cellular functions of APP and its paralogs, we use transgenic Drosophila as a model. Upon overexpression of the APP-family members, transformations of cell fates during the development of the peripheral nervous system were observed. Genetic analysis showed that APP, APLP1 and APLP2 induce Notch gain-of-function phenotypes, identified Numb as a potential target and provided evidence for a direct involvement of Disabled and Neurotactin in the induction of the phenotypes. The severity of the induced phenotypes not only depended on the dosage and the particular APP-family member but also on particular domains of the molecules. Studies with Drosophila APPL confirmed the results obtained with human proteins and the analysis of flies mutant for the appl gene further supports an involvement of APP-family members in neuronal development and a crosstalk between the APP family and Notch.

SUBMITTER: Merdes G

PROVIDER: S-EPMC524346 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila.

Merdes Gunter G Soba Peter P Loewer Alexander A Bilic Michaela V MV Beyreuther Konrad K Paro Renato R

The EMBO journal 20040923 20

The view that only the production and deposition of Abeta plays a decisive role in Alzheimer's disease has been challenged by recent evidence from different model systems, which attribute numerous functions to the amyloid precursor protein (APP). To investigate the potential cellular functions of APP and its paralogs, we use transgenic Drosophila as a model. Upon overexpression of the APP-family members, transformations of cell fates during the development of the peripheral nervous system were o ...[more]

PMID: 15385958

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Project description:As a reference laboratory, the Streptococcus Laboratory at the Centers for Disease Control and Prevention (CDC) is frequently asked to confirm the identity of unusual or difficult-to-identify catalase-negative, gram-positive cocci. In order to accomplish the precise identification of these microorganisms, we have systematically applied analysis of whole-cell protein profiles (WCPP) and DNA-DNA reassociation experiments, in conjunction with conventional physiological tests. Using this approach, we recently focused on the characterization of three strains resembling the physiological groups I (strain SS-1730), II (strain SS-1729), and IV (strain SS-1728) of enterococcal species. Two strains were isolated from human blood, and one was isolated from human brain tissue. The results of physiological testing were not consistent enough to allow confident inclusion of the strains in any of the known enterococcal species. Resistance to vancomycin was detected in one of the strains (SS-1729). Analysis of WCPP showed unique profiles for each strain, which were not similar to the profiles of any previously described Enterococcus species. 16S ribosomal DNA (rDNA) sequencing results revealed three new taxa within the genus ENTEROCOCCUS: The results of DNA-DNA relatedness experiments were consistent with the results of WCPP analysis and 16S rDNA sequencing, since the percentages of homology with all 25 known species of Enterococcus were lower than 70%. Overall, the results indicate that these three strains constitute three new species of Enterococcus identified from human clinical sources, including one that harbors the vanA gene. The isolates were provisionally designated Enterococcus sp. nov. CDC Proposed New Species of Enterococcus 1 (CDC PNS-E1), type strain SS-1728(T) (= ATCC BAA-780(T) = CCUG 47860(T)); Enterococcus sp. nov. CDC PNS-E2, type strain SS-1729(T) (= ATCC BAA-781(T) = CCUG 47861(T)); and Enterococcus sp. nov. CDC PNS-E3, type strain SS-1730(T) (= ATCC BAA-782(T) = CCUG 47862(T)).

Project description:BACKGROUND:Dual tasking constitutes a large portion of most activities of daily living; in real-life situations, people need to not only maintain balance and mobility skills, but also perform other cognitive or motor tasks at the same time. Interest toward dual-task training (DTT) is increasing as traditional interventions may not prepare patients to adequately face the challenges of most activities of daily living. These usually involve simultaneous cognitive and motor tasks, and they often show a decline in performance. Cognitive-motor interference (CMI) has been investigated in different neurological populations, but limited evidence is present for people with multiple sclerosis (MS). The use of computerized tools is mandatory to allow the application of more standardized assessment and rehabilitation intervention protocols and easier implementation of multicenter and multilanguage studies. OBJECTIVE:To describe the design and development of CMI-APP, an adaptive and interactive technology tablet-based app, and to present the preliminary results of a multicenter pilot study involving people with MS performed in several European centers for evaluating the feasibility of and adherence to a rehabilitation program based on CMI-APP. METHODS:CMI-APP includes user-friendly interfaces for personal data input and management, assessment of CMI, and DTT. A dedicated team developed CMI-APP for Android tablets above API level 14 (version 4.0), using C# as the programming language and Unity and Visual Studio as development tools. Three cognitive assessment tests for working memory, information processing speed, and sustained attention and four motor assessment tests for walking at different difficulty levels were implemented. Dual cognitive-motor tasks were performed by combining single cognitive and motor tasks. CMI-APP implements exercises for DTT involving the following 12 cognitive functions: sustained attention, text comprehension, verbal fluency, auditory discrimination, visual discrimination, working memory, information processing speed, auditory memory, visual memory, verbal analog reasoning, visual analog reasoning, and visual spatial planning, which can be performed during walking or stepping on the spot. Fifteen people with MS (mean age 52.6, SD 8.6 years; mean disease duration 9.4, SD 8.4 years; mean Expanded Disability Status Scale score 3.6, SD 1.1) underwent DTT (20 sessions). Adherence to the rehabilitation program was evaluated according to the percentage of performed sessions, perceived exertion during the training (Borg 15-point Ratings of Perceived Exertion [RPE] Scale), and subjective experience of the training (Intrinsic Motivation Inventory [IMI]). RESULTS:The adherence rate was 91%. DTT was perceived as "somewhat difficult" (mean RPE Scale score 12.6, SD 1.9). IMI revealed that participants enjoyed the training and felt that it was valuable and, to some extent, important, without feelings of pressure. They felt competent, although they did not always feel they could choose the exercises, probably because the therapist chose the exercises and many exercises had few difficulty levels. CONCLUSIONS:CMI-APP is safe, highly usable, motivating, and well accepted for DTT by people with MS. The findings are fundamental for the preparation of future large-sample studies examining CMI and the effectiveness of DTT interventions with CMI-APP in people with MS.

Dataset Information

Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila.

Publications

Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila.

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