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Baier, G.

Publications and source records attributed to Baier, G..

2 recordsLinked to original sources

Network Dynamics In The Healthy And Epileptic Developing Brain

Electroencephalography (EEG) allows recording of cortical activity at high temporal resolution. EEG recordings can be summarised along different dimensions using network-level quantitative measures, e.g. channel-to-channel correlation, or band power distributions across channels. These reveal network patterns that unfold over a range of different time scales and can be tracked dynamically.\n\nHere we describe the dynamics of network-state transitions in EEG recordings of spontaneous brain activity in normally developing infants and infants with severe early infantile epileptic encephalopathies (n=8, age: 1-8 months). We describe differences in measures of EEG dynamics derived from band power, and correlation-based summaries of network-wide brain activity.\n\nWe further show that EEGs from different patient groups and controls can be distinguished based on a small set of the novel quantitative measures introduced here, which describe dynamic network state switching. Quantitative measures related to the smoothness of switching from one correlation pattern to another show the largest differences between groups.\n\nThese findings reveal that the early epileptic encephalopathies are associated with characteristic dynamic features at the network level. Quantitative network-based analyses like the one presented here may in future inform the clinical use of quantitative EEG for diagnosis.

neuroscience

Targeting the PD-1/PD-L1 pathway potentiates immunoediting to counterbalance neutral evolution in a mouse model of colorectal cancer

The cancer immunoediting hypothesis postulates a dual role of the immune system: protecting the host by eliminating tumor cells, and shaping the tumor by editing the genome. However, to what extent immunoediting is shaping the cancer genome is still a matter of debate. Moreover, the impact of cancer immunotherapy with checkpoint blockers on modulating immunoediting remains largely unexplored. Here we elucidated the impact of evolutionary and immune-related forces on editing the tumor in a mouse model of colorectal cancer (CRC). We first show that MC38 cell line is a valid model for hypermutated and microsatellite-unstable (MSI) CRC. Analyses of longitudinal samples of wild type and immunodeficient RAG1 knockout mice transplanted with MC38 cells revealed that upregulation of checkpoint molecules and infiltration of Tregs are the major tumor escape mechanisms. Strikingly, the impact of neutral evolution on sculpting the tumor outweighed immunoediting. Targeting the PD-1/PD-L1 pathway potentiated immunoediting and rendered tumors more homogeneous in the MC38 model. The immunoediting effects were less pronounced in a nonhypermutated/MSI- model CT26. Our study demonstrates that neutral evolution is the major force that sculpts the tumor, and that checkpoint blockade effectively enforces T cell dependent immunoselective pressure in a hypermutated/MSI model of CRC.

genomics