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A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.
Finding a bottle of milk in the bathroom would probably be quite surprising to most of us. Such a surprised reaction is driven by our strong expectations, learned through experience, that a bottle of milk belongs in the kitchen. Our environment is not randomly organized but governed by regularities that allow us to predict what objects can be found in which types of scene. These scene semantics are thought to play an important role in the recognition of objects. But when during development are the semantic predictions so far implemented that such scene-object inconsistencies would lead to semantic processing difficulties? Here we investigated how toddlers perceive their environments, and what expectations govern their attention and perception. To this aim, we used a purely visual paradigm in an ERP experiment and presented 24-month-olds with familiar scenes in which either a semantically consistent or an inconsistent object would appear. The scene-inconsistency effect has been previously studied in adults by means of the N400, a neural marker responding to semantic inconsistencies across many types of stimuli. Our results show that semantic object-scene inconsistencies indeed elicited an enhanced N400 over the left anterior brain region between 750 and 1150 ms post stimulus onset. This modulation of the N400 marker provides first indications that by the age of two toddlers have already established their scene semantics allowing them to detect a purely visual, semantic object-scene inconsistency. Our data suggest the presence of specific semantic knowledge regarding what objects occur in a certain scene category.
Tissue size regulation is critical for the normal functioning of the organ as well as to prevent unwanted pathogenesis such as cancer. The Hippo signaling pathway is well known for its robust regulation of tissue growth by the negative regulation of its nuclear effectors YAP1 and WWTR1. In this study, I have described the role of Yap1/Wwtr1 in zebrafish development, with a primary emphasis on the cardiovascular system.
I have generated zebrafish yap1 and wwtr1 mutants by CRISPR/CAS9. The mutant alleles are likely to be nonfunctional due to a premature stop codon and they show evidence of nonsense-mediated decay. Given that Yap1 and Wwtr1 are closely related proteins and have overlapping functions, I am given the opportunity to perform combinatorial analysis of the mutations on zebrafish development. Together with molecular probing tools, high-throughput sequencing and high-resolution imaging, I showed that
1. Double yap1;wwtr1 mutants exhibit severe posterior elongation phenotype, but somitogenesis appears to proceed as usual.
2. Yap1 and Wwtr1 may play an important role in PCV development and secondary angiogenic sprouting. However, key experiments will be needed to elucidate the direct role of Yap1 and Wwtr1 on these processes.
3. wwtr1-/- larvae hearts have a reduction in trabeculation, but in mosaic WT hearts, mutant cardiomyocytes prefer to populate the trabecular layer. My studies revealed that the mutant compact wall could not support trabeculation, which explains the hypotrabeculation phenotype of wwtr1-/- hearts. Additionally, Wwtr1 is required for myocardial Notch activity and can inhibit compact wall cardiomyocytes from entering the trabecular layer.
In summary, the Hippo signaling pathway, through Yap1/Wwtr1 has important regulatory functions in growth control. My work has revealed a surprising role for Yap1/Wwtr1 in tissue morphogenesis such as posterior tail morphogenesis and specific developmental processes of the cardiovascular system. It will be of interest to elucidate the regulation of Yap1/Wwtr1 in individual cells that translates into the complex cellular behaviors that drives morphogenesis.
A sound and well-functioning legal system will encourage growth in investment and create opportunities for investors. Trademarks as part of intellectual property play an important role in the future development of a country. A mark or symbol is needed in order to give products and services identity and to distinguish them and their qualities from identical or similar products and services of a competitor.
This research studies, examines and analyses the degree, nature and function of trademark protection within the legal system of Afghanistan and compare them with the Paris, Madrid and TRIPs agreements. It has been divided into four chapters: Chapter one provides general information and an overview of the current legal system of Afghanistan. Chapter two studies and analyses international agreements pertaining to the legal protection of trademark. It also critically assesses the ATML compatibility with these agreements: and answers the research question of to what extent the ATML provisions are compatible with them. Chapter three provides information on the different purposes of trademarks from a development perspective and compares the purposes provided by the ATML. Finally, chapter four assesses and examines the acquisition, assignment and termination of trademarks. The conclusions and findings of the thesis are the final section of this research.
Afghanistan, as a transitioning economy, has not developed a solid legal and practical foundation for providing comprehensive protection mechanisms for trademarks as have been articulated in developed countries and international agreements. Accordingly, the Afghan government has not entirely integrated these needs into its legal system and there are some inconsistencies of the ATML with these agreements.
One more challenge is the lack of appropriate legal institutions for issuing, managing, administering and protecting of trademarks. The establishment of a well-functioning administrative institution will serve to fulfil the objectives of the laws. Therefore, the CBR office holds the administrative responsibility for processing the registration of trademarks.
However, the methods and facilities of the CBR office remain outdated, and the office does not have the capacity to provide applicants with up-to-date administrative and technical facilities.
Therefore, legal protection of trademark in Afghanistan is linked not only to the existence of a well functioning of laws, regulations, clear procedures, mechanism and guidelines but also to an efficient and well-functioning administrative office.
The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.
Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.
Der Zwerg-Rohrkolben (Typha minima Funck ex Hoppe) ist eine charakteristische Pionierpflanze von alpinen Wildflusslandschaften. Seit den siebziger Jahren ist diese Kennart jedoch in Deutschland vollständig und in Österreich nahezu ausgestorben. Die anhaltenden Populationsrückgänge der Art sind wahrscheinlich das Ergebnis der weitverbreiteten Flussregulierung und des Kraftwerksbaus in Kombination mit den sehr speziellen Standortsansprüchen der Art. Dank den Anstrengungen von Wiederansiedlungsprogrammen befindet sich T. minima wieder an der Oberen Drau in Österreich. In dieser Publikation wird über die Keimung, das Wachstum, die Reproduktion und die Umweltpräferenzen von T. minima berichtet.
Die Keimungsexperimente von 2014 zeigten eine sehr niedrige mittlere Keimungsrate von 15,6% bei einem Schwankungsbereich von 0–90 %. Die Keimungsraten stiegen mit höheren Temperaturen, erhöhter Saatgutreife und kürzeren Saatgutlagerungszeiten. Nach der Saatgutlagerung von 480 Stunden wurde keine Keimung mehr beobachtet.
Beim FFH-Monitoring 2014 an der Oberen Drau wurden Zwerg-Rohrkolben-Keimlinge (Höhe < 5 cm) generell nur selten gefunden. Die vegetative Jungphase (Höhe > 15 cm, ausschließlich sterile Triebe) wies zumeist den höchsten Flächenanteil im Mittel von 62% auf. Typha minima bildete bis zu einem Alter von ca. 3 Jahren ausschließlich sterile Triebe aus. Ab einem Alter von ca. 9 Jahren wurden auch fertile Triebe mit Blütenständen ausgebildet, wobei deren Anzahl mit zunehmendem Alter sich tendenziell erhöhte. Die Analyse der Standortsfaktoren zeigte, dass T. minima auf eine hohe Bodenfeuchte im Mittel von 39 Vol-% angewiesen ist. Darüber hinaus war der Faktor Beschattung entscheidend. Erst ab einem Beschattungsgrad von 50% durch Weidengebüsche war eine Abnahme der Triebdichte von T. minima zu verzeichnen. Wir schließen daraus, dass T. minima-Populationen während der Keimungsphase extrem empfindlich sind und dass massive Habitatverluste überwiegend das Ergebnis der Flussregulation und der reduzierten Morphodynamik sind, die normalerweise geeignete offene Siedlungsräume für die Keimung des Zwerg-Rohrkolbens schaffen würde.