Urlaub trotz Pflegeabhängigkeit

Hintergrund: In unserer Gesellschaft kommt Urlaub und Reisen eine immer größere Bedeutung zu. Bis vor einiger Zeit galt es als eine Seltenheit, dass Menschen mit Behinderung am allgemeinen Urlaubsgeschehen teilnehmen. Die Nachfrage an Urlaubsmöglichkeiten von Seiten beeinträchtigter Personen ist allerdings in letzter Zeit gestiegen und auch in Zukunft kann mit einer Zunahme gerechnet werden. Besonders für körperbehinderte Menschen existieren im Urlaub unterschiedliche Barrieren und nachteilige Gegebenheiten, die ihnen die Teilnahme daran erschweren. Wie auch der aktuelle Forschungsstand bestätigt, gibt es vor allem im Inland ein großes Defizit an wissenschaftlichen Arbeiten, welche das Thema Urlaub für Menschen mit körperlicher Behinderung behandeln. Infolgedessen scheint die Auseinandersetzung mit dieser Thematik, vor allem aus der Sicht der Betroffenen, aufschlussreich. Ziel: Ziel dieser Arbeit ist es herauszufinden, wie Menschen mit körperlicher Behinderung Urlaub (trotz ihrer Pflegeabhängigkeit) erleben und welche positiven Effekte damit in Verbindung stehen. In erster Linie soll ein Betrag zum Verständnis der Bedeutung von Urlaub bzw. Reisen für Menschen mit körperlicher Behinderung geleistet, auf die Aktualität der Thematik hingewiesen und die verschiedenen Problembereiche dargestellt werden. Methode: Im Rahmen dieser Arbeit wurden zehn Interviews, mittels halbstandardisiertem Interviewleitfaden mit mobilitätsbeeinträchtigten Personen, welche Reiseerfahrung aufweisen (davon acht Rollstuhlfahrer), durchgeführt und anhand der Methode der zirkulären Dekonstruktion ausgewertet. Erkenntnisse: Die Abwechslung vom Alltag, die Erholung und das „Schöpfen von neuer Kraft“ werden von körperbehinderten Urlaubern als Effekte von Urlaub verstanden, die sich positiv auf das alltägliche Leben auswirken. Jene Erfahrungen dienen auch wieder als Motivatoren für weitere Reisen. Eine aufwändige Angelegenheit stellt die Organisation des Urlaubs im Vorhinein dar, da zu den üblichen Vorbereitungen noch zusätzliche hinzukommen. In Bezug auf die Organisation kommt der eigenständigen Überprüfung von Angeboten am meisten Bedeutung zu. Grund dafür sind Probleme in Hinblick auf falsche bzw. mangelhafte Informationen, die Urlauber mit Handikap erhalten. Aufgrund der unterschiedlichen Barrieren, auf welche die Betroffenen im Urlaub stoßen, ist die Anwendung von Bewältigungsstrategien notwendig. Diese lassen sich in drei Kategorien einteilen. Einerseits kommt die Anpassung an Gegebenheiten und andererseits die Anwendung von Handlungsalternativen zum Einsatz. Können diese beiden Strategien nicht angewendet werden, ist ein persönlicher Verzicht unumgänglich. Außerdem spielt die Selbst- bzw. Mitbestimmung im Urlaub eine wesentliche Rolle. Am negativsten nehmen körperbehinderte Urlauber das Verhalten von manchen Mitmenschen wahr, das von Vorurteilen oder Stigmatisierungen geprägt ist. Schlussfolgerung: Die Ergebnisse dieser Arbeit bestätigen Annahmen bereits vorhandener Untersuchungen und bilden eine Ausgangslage für weitere Forschungsarbeiten in diesem Bereich. Urlaub bietet Menschen mit Beeinträchtigung Abwechslung vom alltäglichen Leben und von den oft damit verbundenen Unannehmlichkeiten. Dieser Aspekt weist auf die Wichtigkeit der Publizität und der weiteren Auseinandersetzung mit dieser Thematik hin. Anhand der Ergebnisse aus der bereits existierenden Literatur und der gewonnenen Erkenntnisse können Bereiche identifiziert werden, an denen in Zukunft angesetzt werden sollte, um beeinträchtigten Menschen die Teilnahme am Urlaubsgeschehen zu erleichtern. Defizite existieren in erster Linie in der Gestaltung von Informationsmedien, in der Richtigkeit von Informationen, im Wissen über Menschen mit Behinderung und deren Bedürfnisse und in barrierefrei gestalteten Angeboten

Schwann cells migrate along axons in the absence of GDNF signaling

BACKGROUND: During development neural crest derived Schwann Cell (SC) precursors migrate to nerve trunks and populate nascent nerves. Axonal ensheathment by SC is a prerequisite for normal nerve function and the integrity of myelinated as well as nonmyelinated axons. To provide adequate support functions, SC colonize entire nerves. One important prerequisite for this is their migration into distal axonal regions. RESULTS: Here, we studied the role of Glial cell line derived neurotrophic factor (GDNF), a TGF-beta related growth factor, for SC migration. To this end we used a superior cervical ganglion (SCG) explant-SC migration assay, GDNF null mutant mouse embryos and a chemical inhibitor for GDNF signaling in combination with time-lapse imaging. We found that GDNF signaling is dispensable for SC migration along murine embryonic sympathetic axons. Furthermore, in vivo analyzes revealed that SC migration along the sciatic nerve is also not dependent on GDNF. CONCLUSIONS: In contrast to previous in vitro findings in the sciatic nerve and a SC precursor cell line, our results clearly indicate that GDNF is dispensable for embryonic SC migration. This is demonstrated for the sympathetic nervous system and also for the sciatic nerve in mouse

Interleukin-4 Protects Dopaminergic Neurons In vitro but Is Dispensable for MPTP-Induced Neurodegeneration In vivo

Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson’s disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity. Interleukin 4 (IL4)-mediated M2-like activation of microglia, which is characterized by upregulation of alternative markers Arginase 1 (Arg1) and Chitinase 3 like 3 (Ym1) has been well studied in vitro but the role of endogenous IL4 during CNS pathologies in vivo is not well understood. Interestingly, microglia activation by IL4 has been described to promote neuroprotective and neurorestorative effects, which might be important to slow the progression of neurodegenerative diseases. In the present study, we addressed the role of endogenous and exogenous IL4 during MPP+-induced degeneration of mDA neurons in vitro and further addressed the impact of IL4-deficiency on neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD in vivo. Our results clearly demonstrate that exogenous IL4 is important to protect mDA neurons in vitro, but endogenous IL4 seems to be dispensable for development and maintenance of the nigrostriatal system as well as MPTP-induced loss of TH+ neurons in vivo. These results underline the importance of IL4 in promoting a neuroprotective microglia activation state and strengthen the therapeutic potential of exogenous IL4 for protection of mDA neurons in PD models

IGF-1 Gene Therapy Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergo a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of microglia senescence is of great relevance to understand age‐related declines in cognitive and motor function.We have targeted the deleterious effects of aging by implementing gene therapy with IGF-1, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) IGF-1 gene therapy on aged female rats and evaluated its effect on Caudate-Putamen unit (CPu) gene expression and inflammatory state. IGF-1 gene therapy modified senescent microglia of the CPu towards an anti-inflammatory state increasing the proportion of Iba1+Arg1+ cells. Moreover, IGF-1 gene therapy was able to regulate the pro-inflammatory environment of CPu in female aged rats by down-regulating the expression of genes typically over-expressed during aging. Our results demonstrate that, ICV IGF-1 gene therapy, is capable to modulate microglia cells and CPu gene expression, leading to an improvement in motor function.Instituto de Investigaciones Bioquímicas de La Plat

The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

Background: Genetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein-protein interaction. Methodology/Principal Findings: To further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog of AtLSD1. Subcellular localization analysis of green fluorescent protein (GFP)-tagged PsLSD1 indicates that PsLSD1 is localized in the nucleus. Using a series of GFP-tagged PsLSD1 deletion mutants, we found that the three LSD1-type zinc finger motifs of PsLSD1 alone can target GFP to the nucleus, whereas deletion of the three zinc finger motifs or any individual zinc finger motif causes PsLSD1 to lose its nuclear localization, indicating that the three zinc finger motifs are necessary and sufficient for its nuclear localization. Moreover, site-directed mutagenesis analysis of GFP-tagged PsLSD1 indicates that tertiary structure and basic amino acids of each zinc finger motif are necessary for PsLSD1 nuclear localization. In addition, yeast two-hybrid, pull-down, and BiFC assays demonstrate that the three zinc finger motifs of PsLSD1 directly bind to importin alpha in vitro and in vivo. Conclusions/Significance: Our data demonstrate that the LSD1-type zinc finger motifs of PsLSD1 are a novel nuclear localization signal and directly bind to importin alpha, and suggest that the nuclear import of LSD1 may rely on the interaction between its zinc finger motifs and importin alpha. Moreover, the nuclear localization of PsLSD1 suggests that LSD1 may function as a transcription regulator involved in negatively regulating PCD.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000292929500042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Multidisciplinary SciencesSCI(E)PubMed11ARTICLE7e22131

Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

BackgroundCabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs), which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein.Methodology/Principal FindingsTo determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS) previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2.Conclusions/SignificanceOur results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the existence of similarities and differences in both aspects of Cbt function between the insect and the vertebrate TIEG proteins

Drosophila TIEG Is a Modulator of Different Signalling Pathways Involved in Wing Patterning and Cell Proliferation

Acquisition of a final shape and size during organ development requires a regulated program of growth and patterning controlled by a complex genetic network of signalling molecules that must be coordinated to provide positional information to each cell within the corresponding organ or tissue. The mechanism by which all these signals are coordinated to yield a final response is not well understood. Here, I have characterized the Drosophila ortholog of the human TGF-β Inducible Early Gene 1 (dTIEG). TIEG are zinc-finger proteins that belong to the Krüppel-like factor (KLF) family and were initially identified in human osteoblasts and pancreatic tumor cells for the ability to enhance TGF-β response. Using the developing wing of Drosophila as “in vivo” model, the dTIEG function has been studied in the control of cell proliferation and patterning. These results show that dTIEG can modulate Dpp signalling. Furthermore, dTIEG also regulates the activity of JAK/STAT pathway suggesting a conserved role of TIEG proteins as positive regulators of TGF-β signalling and as mediators of the crosstalk between signalling pathways acting in a same cellular context