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Richardson, A. M.

Publications and source records attributed to Richardson, A. M..

2 recordsLinked to original sources

Image-Based Assessment of Natural Killer Cell Activity against Glioblastoma Stem Cells

Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.

cancer biology↗

Developmentally unique cerebellar processing prioritizes self- over other-generated movements

AO_SCPLOWBSTRACTC_SCPLOWAnimals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self- generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) P8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses to twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models. SO_SCPLOWIGNIFICANCEC_SCPLOW SO_SCPLOWTATEMENTC_SCPLOWFor adult animals to produce flexible and adaptive movements, they must distinguish self- from other-generated movements and learn to anticipate how their body moves through space. The computations required for this capacity occur within the cerebellar system. In early infancy, these computations are not yet established and must develop through sensorimotor experience. Here, we found that self-generated movements--particularly those movements occurring during active sleep--are a preferred source of that sensorimotor experience to the infant cerebellum. This preference appears to be unique to the infant cerebellum and helps us understand how that structure establishes its neural circuitry and functions.

neuroscience↗