| 1. |
- Couillard-Despres, Sebastien, et al.
(author)
-
Doublecortin expression levels in adult brain reflect neurogenesis.
- 2005
-
In: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 21:1, s. 1-14
-
Journal article (peer-reviewed)abstract
- Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions.
|
|
| 2. |
- Gerbitz, Armin, et al.
(author)
-
Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation : results from the randomized phase I/IIa MULTIVIR-01 study
- 2023
-
In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
-
Journal article (peer-reviewed)abstract
- IntroductionAllogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.MethodsWe report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.ResultsThirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DiscussionOur study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02227641.
|
|
| 3. |
- Krampert, Monika, et al.
(author)
-
Smad7 Regulates the Adult Neural Stem/Progenitor Cell Pool in a Transforming Growth Factor β- and Bone Morphogenetic Protein-Independent Manner
- 2010
-
In: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 30:14, s. 3685-3694
-
Journal article (peer-reviewed)abstract
- Members of the transforming growth factor beta (TGF-beta) family of proteins modulate the proliferation, differentiation, and survival of many different cell types. Neural stem and progenitor cells (NPCs) in the adult brain are inhibited in their proliferation by TGF-beta and by bone morphogenetic proteins (BMPs). Here, we investigated neurogenesis in a hypomorphic mouse model for the TGF-beta and BMP inhibitor Smad7, with the hypothesis that NPC proliferation might be reduced due to increased TGF-beta and BMP signaling. Unexpectedly, we found enhanced NPC proliferation as well as an increased number of label-retaining cells in vivo. The enhanced proliferation potential of mutant cells was retained in vitro in neurosphere cultures. We observed a higher sphere-forming capacity as well as faster growth and cell cycle progression. Use of specific inhibitors revealed that these effects were independent of TGF-beta and BMP signaling. The enhanced proliferation might be at least partially mediated by elevated signaling via epidermal growth factor (EGF) receptor, as mutant cells showed higher expression and activation levels of the EGF receptor. Conversely, an EGF receptor inhibitor reduced the proliferation of these cells. Our data indicate that endogenous Smad7 regulates neural stem/progenitor cell proliferation in a TGF-beta- and BMP-independent manner.
|
|
| 4. |
- Winner, Beate, et al.
(author)
-
Dopaminergic lesion enhances growth factor-induced striatal neuroblast migration.
- 2008
-
In: Journal of neuropathology and experimental neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 67:2, s. 105-16
-
Journal article (peer-reviewed)abstract
- Adult neurogenesis persists in the subventricular zone and is decreased in Parkinson disease (PD). The therapeutic potential of neurogenesis in PD requires understanding of mechanisms of 1) neural stem cell generation; 2) their guidance to the lesion site; and 3) the environment that enables neuronal differentiation, survival, and functional integration. We examined the combined intraventricular infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) in a 6-hydroxydopamine-induced rodent model of PD. Epidermal growth factor and FGF-2 induced a massive increase in cell proliferation and in numbers of doublecortin-expressing neuroblasts in the subventricular zone. These growth factors also increased dopaminergic neurogenesis in the olfactory bulb and promoted the migration of newly generated neuroblasts from the subventricular zone into the adjacent striatum. The effects of EGF and FGF-2 were present in unlesioned animals but were dramatically enhanced in 6-hydroxydopamine-lesioned animals.These findings suggest that newly generated neuroblasts may be redirected to the region of dopaminergic deficit, and that EGF and FGF-2 can enhance dopaminergic neurogenesis in the olfactory bulb but not in the striatum. Similar mechanisms may be involved in the increased numbers of dopaminergic neurons observed in the olfactory bulbs of PD patients and their functional olfactory deficits.
|
|
| 5. |
- Winner, Beate, et al.
(author)
-
Human wild-type alpha-synuclein impairs neurogenesis.
- 2004
-
In: Journal of neuropathology and experimental neurology. - 0022-3069. ; 63:11, s. 1155-66
-
Journal article (peer-reviewed)abstract
- Neurodegenerative diseases classified as synucleinopathies are characterized by alpha-synuclein inclusions. In these disorders, alpha-synuclein accumulates within glial or neuronal cells in the brain including regions of adult neurogenesis. We hypothesized a pathophysiological role for alpha-synuclein in newly generated cells of the adult brain and in this study examined regions of neurogenesis in adult mice overexpressing human wild-type alpha-synuclein under the control of the platelet-derived growth factor promoter. The number of proliferating cells and the fate of newly generated cells were analyzed in the olfactory bulb system and in the hippocampal dentate gyrus. There were no effects on proliferation detectable; however, significantly less neurogenesis and fewer neurons were observed in the olfactory bulb as well as in the hippocampus of adult human alpha-synuclein mice compared to control littermates. This effect was almost exclusively due to diminished survival of neuronal precursors in the target regions of neurogenesis. Our data imply that the finely tuned equilibrium of neuronal cell birth and death in neurogenic regions may be altered in human alpha-synuclein-overexpressing mice. We hypothesize that reduced adult neurogenesis in the olfactory bulb may contribute to olfactory deficits in neurodegenerative disorders associated with alpha-synuclein inclusions.
|
|
| 6. |
- Winner, Beate, et al.
(author)
-
Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.
- 2006
-
In: Experimental neurology. - : Elsevier BV. - 0014-4886. ; 197:1, s. 113-21
-
Journal article (peer-reviewed)abstract
- Dopaminergic loss is known to be one of the major hallmarks of Parkinson disease (PD). In addition to its function as a neurotransmitter, dopamine plays significant roles in developmental and adult neurogenesis. Both dopaminergic deafferentation and stimulation modulate proliferation in the subventricular zone (SVZ)/olfactory bulb system as well as in the hippocampus. Here, we study the impact of 6-hydroxydopamine (6-OHDA) lesions to the medial forebrain bundle on proliferation and neuronal differentiation of newly generated cells in the SVZ/olfactory bulb axis in adult rats. Proliferation in the SVZ decreased significantly after dopaminergic deafferentation. However, the number of neural progenitor cells expressing the proneuronal cell fate determinant Pax-6 increased in the SVZ. Survival and quantitative cell fate analysis of newly generated cells revealed that 6-OHDA lesions induced opposite effects in the two different regions of neurogenesis in the olfactory bulb: a transient decrease in the granule cell layer contrasts to a sustained increase of newly generated neurons in the glomerular layer. These data point towards a shift in the ratio of newly generated interneurons in the olfactory bulb layers. Dopaminergic neurogenesis in the glomerular layer tripled after lesioning and consistent with this finding, the total number of tyrosine hydroxylase (TH)-positive cells increased. Thus, loss of dopaminergic input to the SVZ led to a distinct cell fate decision towards stimulation of dopaminergic neurogenesis in the olfactory bulb glomerular layer. This study supports the accumulating evidence that neurotransmitters play a crucial role in determining survival and differentiation of newly generated neurons.
|
|
| 7. |
- Aigner, Wolfgang, et al.
(author)
-
Workshop on Audio-Visual Analytics
- 2022
-
In: PROCEEDINGS OF THE WORKING CONFERENCE ON ADVANCED VISUAL INTERFACES AVI 2022. - New York, NY, USA : ASSOC COMPUTING MACHINERY. - 9781450397193
-
Conference paper (peer-reviewed)abstract
- In their daily lives, people use more than one sense to perceive and interpret their environment. Likewise, audio-visual interfaces can support human data analysts better than interfaces relying on just one sense. While the research communities of sonification and visualization have both carried out extensive research on the auditory and visual representation of data, comparatively little is known about their systematic and complementary combination for data analysis. After two workshops at Audio Mostly 2021 and IEEE VIS, this 3rd workshop on audio-visual analytics continues building a community of researchers interested in combining visualization and sonification.
|
|
| 8. |
- Ambros, Inge M, et al.
(author)
-
A multilocus technique for risk evaluation of patients with neuroblastoma.
- 2011
-
In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 17:4, s. 792-804
-
Journal article (peer-reviewed)abstract
- Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma.
|
|
| 9. |
- Elmquist, Elias, 1996-, et al.
(author)
-
Parallel Chords: an audio-visual analytics design for parallel coordinates
- 2024
-
In: Personal and Ubiquitous Computing. - : Springer. - 1617-4909 .- 1617-4917.
-
Journal article (peer-reviewed)abstract
- One of the commonly used visualization techniques for multivariate data is the parallel coordinates plot. It provides users with a visual overview of multivariate data and the possibility to interactively explore it. While pattern recognition is a strength of the human visual system, it is also a strength of the auditory system. Inspired by the integration of the visual and auditory perception in everyday life, we introduce an audio-visual analytics design named Parallel Chords combining both visual and auditory displays. Parallel Chords lets users explore multivariate data using both visualization and sonification through the interaction with the axes of a parallel coordinates plot. To illustrate the potential of the design, we present (1) prototypical data patterns where the sonification helps with the identification of correlations, clusters, and outliers, (2) a usage scenario showing the sonification of data from non-adjacent axes, and (3) a controlled experiment on the sensitivity thresholds of participants when distinguishing the strength of correlations. During this controlled experiment, 35 participants used three different display types, the visualization, the sonification, and the combination of these, to identify the strongest out of three correlations. The results show that all three display types enabled the participants to identify the strongest correlation — with visualization resulting in the best sensitivity. The sonification resulted in sensitivities that were independent from the type of displayed correlation, and the combination resulted in increased enjoyability during usage.
|
|
| 10. |
- Enge, Kajetan, et al.
(author)
-
Open Your Ears and Take a Look: A State‐of‐the‐Art Report on the Integration of Sonification and Visualization
- 2024
-
In: Computer graphics forum (Print). - : Wiley-Blackwell Publishing Inc.. - 0167-7055 .- 1467-8659. ; 43:3
-
Journal article (peer-reviewed)abstract
- The research communities studying visualization and sonification for data display and analysis share exceptionally similar goals, essentially making data of any kind interpretable to humans. One community does so by using visual representations of data, and the other community employs auditory (non-speech) representations of data. While the two communities have a lot in common, they developed mostly in parallel over the course of the last few decades. With this STAR, we discuss a collection of work that bridges the borders of the two communities, hence a collection of work that aims to integrate the two techniques into one form of audiovisual display, which we argue to be “more than the sum of the two.” We introduce and motivate a classification system applicable to such audiovisual displays and categorize a corpus of 57 academic publications that appeared between 2011 and 2023 in categories such as reading level, dataset type, or evaluation system, to mention a few. The corpus also enables a meta-analysis of the field, including regularly occurring design patterns such as type of visualization and sonification techniques, or the use of visual and auditory channels, showing an overall diverse field with different designs. An analysis of a co-author network of the field shows individual teams without many interconnections. The body of work covered in this STAR also relates to three adjacent topics: audiovisual monitoring, accessibility, and audiovisual data art. These three topics are discussed individually in addition to the systematically conducted part of this research. The findings of this report may be used by researchers from both fields to understand the potentials and challenges of such integrated designs while hopefully inspiring them to collaborate with experts from the respective other field.
|
|
