7 research outputs found
Analyse der Wurzelarchitektur von Gerste (<em>Hordeum vulgare</em>) unter verschiedenen Umweltbedingungen
Innerhalb der letzten Jahre zeigte der Aufruf zu einer "second green revolution" die Notwendigkeit zur Entwicklung leistungsfĂ€higer Kulturpflanzen mit robustem Verhalten auf wechselnde Umweltbedingungen und limitierte NĂ€hrstoffangebote. Die Pflanzenwurzel spielt eine zentrale Rolle bei der Versorgung der Pflanze mit NĂ€hrstoffen und Wasser, und die Wurzelarchitektur hat demnach Einfluss auf die Entwicklung und ProduktivitĂ€t der Pflanze. Die Wurzelarchitektur wurde aufgrund methodischer Schwierigkeiten wenig erforscht und daher als mögliches Kriterium zur verbesserten Selektion in der PflanzenzĂŒchtung wenig berĂŒcksichtigt. In der vorliegenden Arbeit wurde als Teilprojekt des Verbundvorhabens âPhenomics, Transcriptomics und Genomics - ein integrierter Ansatz zur Effizienzsteigerung in der Selektion trockenstresstoleranter Gersteâ die Wurzelarchitektur von 6 deutschen Sommerbraugersten (Hordeum vulgare, L. cv. Wisa, LfL24727, Barke, Grace, Braemar, Tatum) zerstörungsfrei im Labor untersucht. Zur Erfassung der Wurzelarchitektur wurden die Gerstensamen oberflĂ€chensterilisiert und in einem transparenten Wachstumsmedium in einem axenischen System angezogen. Die Gerstenpflanzen wurden unter verschiedenen Umweltbedingungen, d. h. unter osmotischem Stress, Phosphatmangel und Nitratmangel sowie unter Kontrollbedingungen angezogen. AnschlieĂend erfolgte auf einer speziell angefertigten, rotierenden Bildaufnahme-Plattform die digitale Bildaufnahme des Wurzelsystems der juvenilen Pflanzen nach 16 Tagen Wachstum. Dabei entstanden pro Pflanze bis zu 36 Aufnahmen des Wurzelsystems in einer vollen 360° Umdrehung. Die Digitalbilder des Wurzelsystems wurden zur Berechnung von diversen Parametern, mit welchen die Wurzelarchitektur beschrieben werden kann, verwendet. Dies erfolgte mit dem Einsatz einer dafĂŒr entwickelten Bildverarbeitungssoftware. Die Software GiA Roots wurde in Kooperation verschiedener Arbeitsgruppen von Prof. Dr. Philip Benfey, Duke University, Durham NC, USA entwickelt und ermöglicht die Berechnung von 19 verschiedenen Wurzelparametern aus Bilderserien. Pro Gerstensorte und Behandlung wurden von mindestens 10 Individuen die Wurzelarchitektur-Parameter mit GiA Roots 2D (Iyer-Pascuzzi et al., 2010; Galkovskyi et al., 2012) berechnet und anschlieĂend statistisch ausgewertet. Die Ziele dieser Arbeit waren, neben der Etablierung der Anzuchtmethoden der Gerste im axenischen System und der Etablierung einer Hochdurchsatz Bildaufnahme- und Bildverarbeitungspipeline im Labor vor Ort, die zerstörungsfreie Untersuchung der verwendeten Gerstensorten auf phĂ€notypische Unterschiede, um die Robustheit des Wurzelsystems bzgl. der verschiedenen Umweltbedingungen zu charakterisieren. Die Analysen ergaben, dass die Wurzelarchitektur der 6 Sommergersten statistisch signifikante Unterschiede auf einem 5% Niveau bei vielen der gemessenen Wurzelparameter aufweist. Bei Wachstum unter Kontrollbedingungen wurden zwei Wurzel-PhĂ€notypen festgestellt, die Sorten Grace und Barke besitzen ein kleineres Wurzelsystem im Vergleich zu den Sorten Wisa, LfL24727, Braemar und Tatum. Auch zeigten sich unterschiedlich stark ausgeprĂ€gte Reaktionen der Sorten bzgl. der Stressversuche. Die Sorten Grace und Braemar zeigten eine, wie in der Literatur unter osmotischem Stress beschriebene, angepasste VerĂ€nderung ihrer Wurzelarchitektur. Die Sorten LfL24727, Grace, Braemar und Tatum zeigten auĂerdem ein an Phosphatmangel adaptiertes Wurzelsystem. Unter Nitratmangel wurden unterschiedlich starke, signifikante VerĂ€nderungen der Wurzelarchitektur bei jeder der getesteten Sorten beobachtet. Da die Sorten Grace und Braemar auf alle Stressversuche ein adaptiertes Verhalten des Wurzelsystems zeigten, wurden sie als robuste Sorten eingestuft. Die jeweiligen Reaktionen des juvenilen Wurzelsystems können genutzt werden, um auf bestimmte Eigenschaften der Sorten RĂŒckschlĂŒsse zu ziehen. Dies bietet den PflanzenzĂŒchtern die Möglichkeit, kombiniert mit ihren Erfahrungen ĂŒber die Eigenschaften der Sorten, die hier beschriebene Methode zur Analyse der Wurzelarchitektur juveniler Gerste als zusĂ€tzliches Instrument zur Beurteilung von Sorten einzusetzen.Analysis of root system architecture (RSA) of six spring barley varieties under different environmental conditions Within the last years the call to a "second green revolution" showed the need for the development of efficient crops with robust behavior at varying environmental conditions and limited nutrient constraints. The plantsâ root system plays a central role in plant nutrition and, therefore, the root architecture has influence on the development and productiveness of a plant. However, because of the methodical difficulties little attention was investigated to explore the root architecture and, hence, it was long ignored as a possible selection criterion for improved plant breeding. In the present work, the root architecture of 6 German spring barley varieties (Hordeum vulgare, L. cv. Wisa, LfL24727, Barke, Grace, Braemar and Tatum) was examined using a non-destructive approach. This was a sub project of the research project âPhenomics, Transcriptomics und Genomics - ein integrierter Ansatz zur Effizienzsteigerung in der Selektion trockenstresstoleranter Gersteâ. To study the root architecture, the barley seeds were surface sterilized and grown in a transparent gellan gum under sterile conditions. Plants were grown under differential environmental conditions (osmotic stress, phosphate and nitrogen deficiency and control conditions). To obtain images of the 16-days-old roots, plants were imaged on a semi-automated rotating imaging platform. Up to 36 images per plant were captured every 10° through a full 360° rotation. Out of these images 19 root architecture parameters were calculated using GiA Roots software (Iyer-Pascuzzi et al., 2010). In cooperation with different working groups, GiA Root was developed by Prof. Dr. Philip Benfey, Duke University, Durham NC, USA. It was developed as a high-throughput image analyzing pipeline for image series and allows 19 different root architecture parameters to be considered. In this work more than 10 individuals of each barley variety and each treatment were used for image analysis followed by statistical analysis. The objectives of this work were to establish the plant culture methods and the imaging-pipeline and the analysis of the barley plants for phenotypic characteristics to evaluate the robustness of the roots under different conditions. Statistical analysis revealed that many significant differences exist at 5 per cent between the cultivarsâ root parameter. Two different root phenotypes were identified grown on control medium. The varieties Barke and Grace showed a comparably small root system in contrast to the cultivars LfL24727, Grace, Braemar and Tatum. The root system responded differently to the stress treatments. The cultivars Grace and Braemar showed an adaptive reaction of the root system to osmotic stress. The cultivars LfL24727, Grace, Braemar and Tatum changed their root architecture and showed a smaller and more branched root system at the ground surface. Under nitrate deficiency all the cultivars showed distinct responses of the root system. The cultivars Grace and Braemar exhibited the most adaptive reaction and are therefore considered to be robust cultivars. The respective reactions of the juvenile root system can be used to draw conclusions on certain qualities of the cultivars. This offers the plant breeders the possibility to use this imaging system as an additional instrument for breeding selection
Stage-dependent biomarker changes in spinocerebellar ataxia type 3
Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of spinocerebellar ataxia type 3/Machado-Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. ANN NEUROL 2024;95:400-406T.K., M.S., L.S., J.I., and B.vdW. are members of the European Reference Network for Rare Neurological Diseases (ERN-RD, project number 739510). The ESMI consortium acknowledges Ruth Hossinger for the project management of the ESMI project and for all contributions made toward the success of this project. This publication is an outcome of ESMI, an EU Joint Program â Neurodegenerative Disease Research (JPND) project (see www.jpnd.eu). The project is supported through the following funding organisations under the aegis of JPND: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organization for Health Research and Development; Portugal, Fundaçao para a CiĂȘncia e Tecnologia (funding code JPCOFUND/ 0002/2015); United Kingdom, Medical Research Council (MR/N028767/1). This project has received funding from the European Unionâs Horizon 2020 research and innovation program under grant agreement No. 643417. The Azores ESMI Network is currently supported by the Regional Government (Fundo Regional para a CiĂȘncia e a Tecnologia-FRCT), under the PRO-SCIENTIA program. At the USA sites, this work was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS080816. The Center for Magnetic Resonance Research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant P41 EB027061, the Institutional Center Cores for Advanced Neuroimaging award P30 NS076408 and S10 OD017974 grant. T.K. received research support from the Bundesministerium fĂŒr Bildung und Forschung (BMBF), the National Institutes of Health (NIH) and Servier. J.F. received funding as a Fellow of the Hertie Network of Excellence in Clinical Neuroscience. M.R. is supported by FCT (CEECIND/03018/2018). B.vdW. received funding from ZonMw, NWO, Gossweiler Foundation, Brugling Fonds, Radboudumc, Hersenstichting, and Christina Foundation. C.O. received funding from NINDS #U01 NS104326; the National Ataxia Foundation; and Robert and Nancy Hall Brain Research Fund. J.S. is supported in part by the National Ataxia Foundation, the Raynor Cerebellum Project, and the MINDlink Foundation. J.J. received grant support from NIH and Friedrichâs Ataxia Research Alliance (FARA). A.T. received research grants from the University Medicine Essen Clinician Scientist Academy (UMEA)/Deutsche Forschungsgemeinschaft (DFG, grant number: FU356/12-2). At the Portuguese sites, M.M.S. and L.P-A. received funding from European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Program, and through the COMPETE 2020 â Operational Program for Competitiveness and Internationalization; and Portuguese national funds via FCT â Fundaçao para a CiĂȘncia e a Tecnologia, under the projects: CENTRO-01-0145-FEDER-181240, 2022.06118.PTDC, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, ViraVector (CENTRO-01-0145-FEDER-022095), Fighting Sars-CoV-2 (CENTRO-01-01D2-FEDER-000002), BDforMJD (CENTRO-01-0145-FEDER-181240 & 2022.06118.PTDC), ModelPolyQ2.0 (CENTRO-01-0145- FEDER-181258), and MJDEDIT (CENTRO-01-0145- FEDER-181266); ARDAT under the IMI2 JU Grant agreement No 945473 supported by the European Unionâs H2020 program and EFPIA; by the American Portuguese Biomedical Research Fund (APBRF), National Ataxia Foundation, and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund. P.S. and M.M.P. were supported by FCT under the fellowship grant SFRH/BD/148451/2019, and 2019 and 2022.11089.BD. C.W. was supported by the Clinician Scientist Program of the Medical Faculty TĂŒbingen (480-0-0). P.G. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center UCLH. P.G. also receives support from the North Thames CRN. P.G. and H.G-M work at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Healthâs National Institute for Health Research Biomedical Research Centerâs funding scheme. P.G. received funding from the Medical Research Council (MR/N028767/1) and CureSCA3 in support of H.G-Mâs work
Cerebellar Volumetry in Ataxias: Relation to Ataxia Severity and Duration
Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Our results (i) confirmed SCA6 being considered as a pure cerebellar grey matter disease, (ii) emphasise the involvement of cerebellar white matter in the neuropathology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C
Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3
Background: Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity. Objective: The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease. Methods: We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels. Results: The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume. Conclusion: Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Evolution of disability in spinocerebellar ataxias type 1, 2, 3, and 6
International audienceObjective: The aim was to study the evolution of disability in spinocerebellar ataxias (SCAs) type 1, 2, 3, and 6 (SCA1, 2, 3, 6). Methods: We analyzed data of two longitudinal cohorts (RISCA, EUROSCA) which recruited ataxic and non-ataxic SCA1, SCA2, SCA3, and SCA6 mutation carriers. To study disability, we used a five-stage system for ataxia defined by walking ability (stages 0-3) and death (stage 4). Transitions were analyzed using a multi-state model with proportional transition hazards. Based on the hazard estimates, transition probabilities and the expected lengths of stay in each stage were calculated. We further studied the effect of sex and CAG repeat length on progression. Results: Data of 3138 visits in 677 participants were analyzed. Median SARA scores for SCA1, SCA2, SCA3, and SCA6 ranged from 1.5 (interquartile range [IQR] = 0.0-3.5) to 3.5 (IQR = 1.4-6.1) in stage 0, 11.5 (IQR = 9.6-14.0) to 13.8 (IQR = 11.0-16.0) in stage 1, 19.0 (IQR = 17.0-21.0) to 23.8 (IQR = 19.5-27.0) in stage 2, and 28.5 (IQR = 26.0-32.5) to 34.0 (IQR = 32.6-37.1) in stage 3. Modeling allowed to calculate the subtype-specific probability to be in a certain stage at a given age and duration of each stage. CAG repeat length was associated with faster progression in SCA1 (HR, 95% CI: 1.1, 1.1-1.2), SCA2 (1.2, 1.1-1.3), and SCA3 (1.1, 1.0-1.2). In SCA6, female sex was associated with faster progression (1.7, 1.1-2.6). Interpretation: Our data are important for counselling of patients, assessment of the relevance of outcome markers, and design of clinical trials
Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult-Onset Degenerative Ataxia
BackgroundSporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA). ObjectivesTo study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers. MethodsSPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed-effects models, we analyzed changes on a time scale starting with ataxia onset. ResultsOf 404 patients without genetic diagnosis, 130 met criteria of probable MSA-C at baseline and 26 during follow-up suggesting clinical conversion to MSA-C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA-C from SAOA. NfL decreased in MSA-C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA-C. In MSA-C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA-C. ConclusionsThis study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. (c) 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Stage-dependent biomarker changes in spinocerebellar ataxia type 3
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, while neurofilament light deviated from normal 13.3âyears before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2âyears and 0.6âyears before ataxia onset. We propose a staging model of SCA3 that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset