Lopes, T. | bioRxiv Science

bioRxiv2018

Aneuploidy Promotes Intestinal Dysplasia in Drosophila

Aneuploidy is associated with different human diseases, particularly cancer, but how different cell types within tissues respond to aneuploidy is not fully understood. In some studies, aneuploidy has been shown to have a deleterious effect and lead to cell death, however it has also been shown to be a causal event of tumorigenesis in other contexts.\n\nHere, we show that Drosophila intestinal stem cells have a particular tolerance to aneuploidy and do not activate apoptosis in response to chromosome misegregation like other non-stem cells. Instead, we observe the development of tissue dysplasia characterized by an accumulation of progenitor cells, increased stem cell proliferation rate, and an excess of cells of the enteroendocrine lineage. Our findings highlight the importance of mechanisms acting to prevent aneuploidy within tissue stem cells and provide an in vivo model of how these cells can act as reservoirs for genomic alterations that can lead to dysplasia.

developmental biology↗

bioRxiv2017

Default Mode Network patterns and its interactions with memory performance in patients with Temporal Lobe Epilepsy and controls

Objectiveto investigate abnormal functional connectivity in the resting-state default mode network (DMN) and its relation to memory impairments in patients with temporal lobe epilepsy with and without hippocampal sclerosis (HS)\n\nMethodwe enrolled 122 MTLE patients divided into right-HS (n=42), left-HS (n=49), MRI-negative MTLE (n=31) and controls (n=69). All underwent resting-state seed-based connectivity fMRI, with a seed placed at the posterior cingulate cortex, an essential node for the DMN. In addition, patients and 41 controls were tested for verbal and visual memory, estimated intelligence coefficient and delayed recall.\n\nResultsBoth right-HS and MRI-negative group presented the poorest visual memory scores, and right-HS and left-HS had a worse performance in verbal memory compared to controls and MRI-negative groups. As expected, hippocampus was less connected than controls in all groups of patients. Although EEGs indicated that 64.5% of MRI-negative patients were lateralized to the left, this group showed activations similar to the right-HS.\n\nConclusionOur data suggest that there is a disruption of the normal pattern of DMN in MTLE. Patients with left and right-HS presented similar, increased and decreased connectivity in the ipsilateral hemisphere; however, left-HS had abnormal decreased connectivity in the contralateral hemisphere. Per neuropsychological examination, the presence of HS in the left hemisphere had more impact on verbal memory, which was not found when the seizure focus is in the left hemisphere in the absence of HS. The absence of hippocampal atrophy seems to yield a less prominent disruption in both functional connectivity and neuropsychological performance.

neuroscience↗