Biology subjects

Kessel, R.

Publications and source records attributed to Kessel, R..

3 recordsLinked to original sources

bioRxiv2023

Ribosomal protein control of hematopoietic stem cell transformation through direct, non-canonical regulation of metabolism

We report here that expression of the ribosomal protein, RPL22, is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); and, reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from altered metabolism including increased fatty acid oxidation (FAO) and a striking induction of the stemness factor Lin28b in the resulting leukemia. Lin28b promotes a substantial increase in lipid content, upon which the survival of Rpl22-deficient leukemias depends. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSC through regulation of FAO and promotes leukemogenesis through Lin28b promotion of lipid synthesis. HighlightsO_LIRPL22 insufficiency is observed in MDS/AML and is associated with reduced survival C_LIO_LIRpl22-deficiency produces an MDS-like syndrome and facilitates leukemogenesis C_LIO_LIRpl22-deficiency does not impair global protein synthesis by HSC C_LIO_LIRpl22 controls leukemia survival through control of lipid synthesis C_LI eTOC: Rpl22 controls the function and transformation potential of hematopoietic stem cells through regulation of lipid metabolism.

cancer biology↗

bioRxiv2020

Distinct Neuronal Populations Contribute to Trace Conditioning and Extinction Learning in the Hippocampal CA1

Trace conditioning and extinction learning depend on the hippocampus, but it remains unclear how ongoing neural activities in the hippocampus are modulated during different learning processes. To explore this question, we performed calcium imaging in a large number of individual CA1 neurons during both trace eye-blink conditioning and subsequent extinction learning in mice. Using trial-averaged calcium fluorescence analysis, we found direct evidence that in real time, as learning emerges, distinct populations of CA1 cells contribute to trace conditioned learning versus extinction learning. Furthermore, we examined network connectivity by calculating co-activity between CA1 neuron pairs, and found that CA1 network connectivity is different between conditioning and extinction and between correct versus incorrect behavioral responses during trace conditioned learning. However, the overall connectivity density remains constant across these behavioral conditions. Together, our results demonstrate that distinct populations of CA1 neurons, forming different sub-networks with unique connectivity patterns, encode different aspects of learning.

neuroscience↗

bioRxiv2018

A Teensy microcontroller-based interface for optical imaging camera control during behavioral experiments

BackgroundSystems neuroscience experiments often require the integration of precisely timed data acquisition and behavioral monitoring. While specialized commercial systems have been designed to meet various needs of data acquisition and device control, they often fail to offer flexibility to interface with new instruments and variable behavioral experimental designs. New methodWe developed a Teensy 3.2 microcontroller-based interface that offers high-speed, precisely timed behavioral data acquisition and digital and analog outputs for controlling sCMOS cameras and other devices. ResultsWe demonstrate the flexibility and the temporal precision of the Teensy interface in two experimental settings. We first used the Teensy interface for reliable recordings of an animals directional movement on a spherical treadmill, while delivering repeated digital pulses that can be used to control image acquisition from a sCMOS camera. In another example, we used the Teensy interface to control temporally precise delivery of an auditory stimulus and a gentle eye puff in a trace conditioning eye blink behavioral paradigm, while delivering repeated digital pulses to initiate camera image acquisition. Comparison with existing methodsThis interface allows high-speed and temporally precise digital data acquisition and device control during diverse behavioral experiments. ConclusionThe Teensy interface, consisting of a Teensy 3.2 and custom software functions, provides a temporally precise, low-cost, and flexible platform to integrate sCMOS camera control into behavioral experiments.

neuroscience↗