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Natascia Tiso

Evaluation of Aβ(25-35) in 3D spheroids and zebrafish larvae
Evaluation of caspae 3 staining after treatment with Aβ(25-35) in mice
CD271 (NGFR) is a neurotrophin receptor that belongs to the tumor necrosis receptor (TNFR) family. Upon ligand binding, CD271 can mediate either survival or cell death. Although the role of CD271 as a marker of tumor-initiating cells is... more
CD271 (NGFR) is a neurotrophin receptor that belongs to the tumor necrosis receptor (TNFR) family. Upon ligand binding, CD271 can mediate either survival or cell death. Although the role of CD271 as a marker of tumor-initiating cells is still a matter of debate, its role in melanoma progression has been well documented. Moreover, CD271 has been shown to be upregulated after exposure to both chemotherapy and targeted therapy. In this study, we demonstrate that activation of CD271 by a short β-amyloid–derived peptide (Aβ(25–35)) in combination with either chemotherapy or MAPK inhibitors induces apoptosis in 2D and 3D cultures of eight melanoma cell lines. This combinatorial treatment significantly reduced metastasis in a zebrafish xenograft model and led to significantly decreased tumor volume in mice. Administration of Aβ(25–35) in ex vivo tumors from immunotherapy- and targeted therapy–resistant patients significantly reduced proliferation of melanoma cells, showing that activation ...
The mitochondrial protein IF1 binds to the catalytic domain of the ATP synthase and inhibits ATP hydrolysis in ischemic tissues. Moreover, IF1 is overexpressed in many tumors and has been shown to act as a pro-oncogenic protein, although... more
The mitochondrial protein IF1 binds to the catalytic domain of the ATP synthase and inhibits ATP hydrolysis in ischemic tissues. Moreover, IF1 is overexpressed in many tumors and has been shown to act as a pro-oncogenic protein, although its mechanism of action is still debated. Here, we show that ATP5IF1 gene disruption in HeLa cells decreases colony formation in soft agar and tumor mass development in xenografts, underlining the role of IF1 in cancer. Notably, the lack of IF1 does not affect proliferation or oligomycin-sensitive mitochondrial respiration, but it sensitizes the cells to the opening of the permeability transition pore (PTP). Immunoprecipitation and proximity ligation analysis show that IF1 binds to the ATP synthase OSCP subunit in HeLa cells under oxidative phosphorylation conditions. The IF1–OSCP interaction is confirmed by NMR spectroscopy analysis of the recombinant soluble proteins. Overall, our results suggest that the IF1-OSCP interaction protects cancer cells...
The transcription factor STAT3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent STAT3-reporter zebrafish based on repeats of minimal responsive elements. These... more
The transcription factor STAT3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent STAT3-reporter zebrafish based on repeats of minimal responsive elements. These transgenic lines mimic in vivo STAT3 expression patterns and are responsive to exogenous STAT3; notably, fluorescence is inhibited by both stat3 knock-out and IL6/JAK/STAT inhibitors. At larval stages, STAT3 reporter activity correlates with proliferating regions of the brain, haematopoietic tissue and intestine. In the adult gut the reporter is active in sparse proliferating cells, located at the base of intestinal folds, expressing the stemness marker sox9b and having the mammalian Crypt Base Columnar cells morphology; noteworthy, zebrafish stat3 mutants show defects in intestinal folding. The STAT3 reporter activity in the gut is abolished in mutants of Tcf7l2, the intestinal mediator of Wnt/β-catenin-dependent transcription, and the Wnt/β-catenin depend...
Foetal Growth Restriction (FGR), previously known as Intrauterine Growth Restriction (IUGR), is an obstetrical condition due to placental insufficiency, affecting yearly about 30 million newborns worldwide. In this work, we aimed to... more
Foetal Growth Restriction (FGR), previously known as Intrauterine Growth Restriction (IUGR), is an obstetrical condition due to placental insufficiency, affecting yearly about 30 million newborns worldwide. In this work, we aimed to identify and pharmacologically target signalling pathways specifically involved in the FGR condition, focusing on FGR-related cardiovascular phenotypes. The transcriptional profile of human umbilical cords from FGR and control cases was compared with the response to hypoxia of zebrafish (Danio rerio) transgenic lines reporting in vivo the activity of twelve signalling pathways involved in embryonic development. Wnt/β-catenin and Jak/Stat3 were found as key pathways significantly dysregulated in both human and zebrafish samples. This information was used in a chemical-genetic analysis to test drugs targeting Wnt/β-catenin and Jak/Stat3 pathways to rescue a set of FGR phenotypes, including growth restriction and cardiovascular modifications. Treatments wit...
Additional file 5 : Fig.S5. Tbar clusters in responsive neurons. Distributions of neuronal spectral responses classified with Tbar and shown as a function of their overall response to stimuli (quantified by T4D). Comparison of emergence... more
Additional file 5 : Fig.S5. Tbar clusters in responsive neurons. Distributions of neuronal spectral responses classified with Tbar and shown as a function of their overall response to stimuli (quantified by T4D). Comparison of emergence of the different Tbar classes for two different choices of T thresholds.
Additional file 8 : Fig.S8. T distributions at different stimulus intensities for stimulated and control larvae at 5 dpf. Comparison of neuronal response distributions for the four different wavelengths at three different powers.
Background Visually guided behaviors such as optomotor and optokinetic responses, phototaxis, and prey capture are crucial for survival in zebrafish and become apparent after just a few days of development. Color vision, which in... more
Background Visually guided behaviors such as optomotor and optokinetic responses, phototaxis, and prey capture are crucial for survival in zebrafish and become apparent after just a few days of development. Color vision, which in zebrafish is based on a spatially anisotropic tetrachromatic retina, provides an additional important component of world representation driving fundamental larval behaviors. However, little is known about the central nervous system (CNS) circuitry underlying color vision processing downstream of the retina, and its activity correlates with behavior. Here, we used the transparent larva of zebrafish to image CNS neurons and their activity in response to colored visual stimuli. Results To investigate the processing of chromatic information in the zebrafish larva brain, we mapped with cellular resolution, spectrally responsive neurons in the larva encephalon and spinal cord. We employed the genetically encoded calcium indicator GCaMP6s and two-photon microscopy...
<p>A) Integrating our data from this study with previous work we suggest how the initial DRG consisting of bipotent DRG progenitors (black rectangles) become specified (second row) and the resultant cell-fates adopted (bottom row).... more
<p>A) Integrating our data from this study with previous work we suggest how the initial DRG consisting of bipotent DRG progenitors (black rectangles) become specified (second row) and the resultant cell-fates adopted (bottom row). We outline the process in WT (neuron (N, cyan) and glial fates (G, magenta); first column), <i>baz1</i> (neuron only; second column), <i>m618</i> (failure to undergo fate specification; third column) and <i>neurog1</i> mutants (all adopt glia; fourth column). The model summarises at each stage the relative levels of inputs (large font is high activity, small font is weak activity) from each of Sox10, Neurog1, Notch signaling and a Sox10-dependent Factor X, proposed to provide a repressive input on <i>neurog1</i> expression. Colour coding of text indicates function of each input (i.e. Neurog1 drives sensory neuron, Notch signaling and Factor X drive glial specification), but Sox10 (which has independent roles in specification of both fates) is shown in both colours where WT, and in blue in <i>baz1</i> and in black in <i>m618</i> to reflect the neural fate specification activity retained in these mutants. In the case of Sox10 input, note that also font size in neighbouring cells refers to activity with respect to fate being adopted by each cell, since <i>baz1</i> mutant reveals that these roles can be separated. The underlying gene regulatory network is outlined in panel B). Asterisk in <i>m618</i> cells denotes that sensory neuron specification in <i>m618</i> mutants occurs in the absence of Sox10 activity, as a result of Sox9b-mediated transcription of <i>neurog1</i>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172947#pone.0172947.ref013" target="_blank">13</a>]. See text for further details. We note that the data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172947#pone.0172947.g008" target="_blank">Fig 8</a> indicates the possibility that Sox10(baz1) may have unique non-autonomous effects on <u><i>neurog1</i> expression, which, if confirmed, would require modification of the model proposed.</u></p
doi: 10.1152/physiolgenomics.00227.2005 You might find this additional info useful... Supplementary material for this article can be found at:
Zebrafish reporter lines reveal in vivo signaling pathway activities involved in pancreatic cancer
3653 Poster Board III-589 Introduction Human AF9 (alias MLLT3) gene was initially identified as one of the most common translocation partners of MLL associated with acute myeloid leukemia. More recently it has been demonstrated that AF9... more
3653 Poster Board III-589 Introduction Human AF9 (alias MLLT3) gene was initially identified as one of the most common translocation partners of MLL associated with acute myeloid leukemia. More recently it has been demonstrated that AF9 can be a positive regulator of early erythroid/megakaryocytic lineage decisions. However, many biological functions of AF9 and its role in leukemia remain unclear. Here, we aimed to identify the zebrafish homologue of human AF9 and to analyze its function using the zebrafish model system. Methods and Results A single zebrafish af9 gene was identified by homology searching at zebrafish genome database (www.ncbi.nlm.nih.gov/). The putative af9 protein showed 60% identity and 73% similarity to human counterpart. These results from the perspective of phylogenetic and synteny analyses indicated that zebrafish af9 was the likely homologue of human AF9. We used whole-mount in situ hybridization to analyzed its spatial and temporal expression patterns during...
2600 Background AF9 is a transcription factor that plays an essential role in hematopoiesis and embryonic development. The alteration of AF9 is principally associated in acute myeloid leukemia as fusion partner of human MLL (mixed-lineage... more
2600 Background AF9 is a transcription factor that plays an essential role in hematopoiesis and embryonic development. The alteration of AF9 is principally associated in acute myeloid leukemia as fusion partner of human MLL (mixed-lineage leukemia) gene rearrangements. Zebrafish is an excellent model organism to study embryonic development and hematopoiesis. We have previously shown that zebrafish af9 is expressed within the intermediate cell mass (ICM), a site of primitive hematopoiesis in zebrafish. Here we study the loss of af9 in zebrafish development to further understand how af9 modulates early hematopoietic and embryonic development. Methods and results Two morpholino antisense oligos (MOs), designed to block translation and inhibit pre-mRNA splicing of af9, were co-injected in embryos at 1–2 cell stage. To control for off-target effects, two morpholino mismatch oligos were designed and co-injected. Efficacy of MOs was demonstrated by Western blot analysis and RT-PCR in contr...

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