| 1. |
- Dudenhöffer-Pfeifer, Monika, et al.
(author)
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Immunoediting is not a primary transformation event in a murine model of MLL-ENL AML
- 2018
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In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 1:4
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Journal article (peer-reviewed)abstract
- Although it is firmly established that endogenous immunity can prevent cancer outgrowth, with a range of immunomodulatory strategies reaching clinical use, most studies on the topic have been restricted to solid cancers. This applies in particular to cancer initiation, where model constraints have precluded investigations of immunosurveillance and immunoediting during the multistep progression into acute myeloid leukemia (AML). Here, we used a mouse model where the chimeric transcription factor MLL-ENL can be conditionally activated in vivo as a leukemic “first-hit,” which is followed by spontaneous transformation into AML. We observed similar disease kinetics regardless of whether AML developed in WT or immunocompromised hosts, despite more permissive preleukemic environments in the latter. When assessing transformed AML cells from either primary immunocompetent or immunocompromised hosts, AML cells from all sources could be targets of endogenous immunity. Our data argue against immunoediting in response to selective pressure from endogenous immunity as a universal primary transformation event in AML.
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| 2. |
- Schnerwitzki, Danny, et al.
(author)
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Neuron-specific inactivation of Wt1 alters locomotion in mice and changes interneuron composition in the spinal cord
- 2018
-
In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 1:4
-
Journal article (peer-reviewed)abstract
- Locomotion is coordinated by neuronal circuits of the spinal cord. Recently, dI6 neurons were shown to participate in the control of locomotion. A subpopulation of dI6 neurons expresses the Wilms tumor suppressor gene Wt1. However, the function of Wt1 in these cells is not understood. Here, we aimed to identify behavioral changes and cellular alterations in the spinal cord associated with Wt1 deletion. Locomotion analyses of mice with neuron-specific Wt1 deletion revealed a slower walk with a decreased stride frequency and an increased stride length. These mice showed changes in their fore-/hindlimb coordination, which were accompanied by a loss of contralateral projections in the spinal cord. Neonates with Wt1 deletion displayed an increase in uncoordinated hindlimb movements and their motor neuron output was arrhythmic with a decreased frequency. The population size of dI6, V0, and V2a neurons in the developing spinal cord of conditional Wt1 mutants was significantly altered. These results show that the development of particular dI6 neurons depends on Wt1 expression and that loss of Wt1 is associated with alterations in locomotion.
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| 3. |
- Yu, Yang, et al.
(author)
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Neuronal A beta 42 is enriched in small vesicles at the presynaptic side of synapses
- 2018
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In: Life Science Alliance. - : LIFE SCIENCE ALLIANCE LLC. - 2575-1077. ; 1:3
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Journal article (peer-reviewed)abstract
- The amyloid beta-peptide (A beta) is a physiological ubiquitously expressed peptide suggested to be involved in synaptic function, long-term potentiation, and memory function. The 42 amino acid-long variant (A beta 42) forms neurotoxic oligomers and amyloid plaques and plays a key role in the loss of synapses and other pathogenic events of Alzheimer disease. Still, the exact localization of A beta 42 in neurons and at synapses has not been reported. Here, we used super-resolution microscopy and show that A beta 42 was present in small vesicles in presynaptic compartments, but not in postsynaptic compartments, in the neurites of hippocampal neurons. Some of these vesicles appeared to lack synaptophysin, indicating that they differ from the synaptic vesicles responsible for neurotransmitter release. The A beta 42-containing vesicles existed in presynapses connected to stubby spines and mushroom spines, and were also present in immature presynapses. These vesicleswere scarce inother parts of the neurites, where A beta 42 was instead present in large, around 200-600 nm, vesicular structures. Three-dimensional super-resolution microscopy confirmed that A beta 42 was present in the presynapse and absent in the postsynapse.
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