Biology subjects

Care, M.

Publications and source records attributed to Care, M..

3 recordsLinked to original sources

bioRxiv2024

Enforced MYC expression selectively redirects transcriptional programs during human plasma cell differentiation

MYC provides a rheostat linking cell growth and division during plasma cell (PC) differentiation. Precise control of MYC is central to the network controlling differentiation. Deregulation of MYC drives transformation in aggressive B-cell neoplasms and is often accompanied by apoptotic protection conferred by BCL2. We assess how MYC and BCL2 deregulation impacts on the ability of human B-cells to complete PC differentiation. Under permissive conditions for PC differentiation we find such deregulation does not transform cells. While driving loss of normal PC surface phenotype, MYC deregulation has little impact on components of regulatory circuitry controlling B-cell identity. This contrasts with profound impact on initiation of secretory output and secretory reprogramming, coupled to dampening of XBP1 and immunoglobulin gene enhancement and a shift toward distinct metabolic programs. The establishment of this aberrant state depends on MYC homology boxes (MB0 and MBII). Dependence on MBII is profound and resolves to residue W135.

cell biology↗

bioRxiv2023

Enabling Model-based Design for closed-loop applications in neuroengineering

This study addresses the inherent difficulties in the creation of neuroengineering devices for closed-loop stimulation, a task typically characterized by intricate and technically demanding processes. Beneath the substantial hardware advancements in neurotechnology, there is often rather complex low-level code that poses challenges in terms of development, documentation, and long-term maintenance. To overcome these obstacles, we adopted an alternative strategy centered on Model-based Design (MBD) as a means to simplify the creation of closed-loop systems and reduce the entry barriers. MBD offers distinct advantages by streamlining the development workflow and facilitating the implementation of intricate systems. In this study, we applied MBD techniques to implement a spike detection algorithm on a Field-Programmable Gate Array (FPGA) using commercially available hardware that combines neural probe electronics with programmable FPGA-based hardware. The entire process of data handling and data processing was designed within the Simulink(R) environment, with subsequent generation of HDL code tailored to the FPGA hardware. The validation of our approach was conducted through in vivo experiments involving six animals. We have made all project code files open-source, thereby providing free access to fellow scientists interested in the development of closed-loop systems.

bioengineering↗

bioRxiv2023

IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy

Glioblastoma (GBM) brain tumours lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumours almost always fatally recur. Using RNAseq data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumours, we identified two responder subtypes based on therapy-driven changes in gene expression. In two thirds of patients a specific subset of genes is up-regulated from primary to recurrence (Up responders) and in one third the same genes are down-regulated (Down responders). Characterisation of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms. In Up responders treatment enriches for quiescent proneural GBM stem cells and differentiated neoplastic cells with increased neurotransmitter signalling, whereas Down responders commonly undergo therapy-driven mesenchymal transition. Stratifying GBM tumours by response subtype may lead to more effective treatment. In support of this, modulators of gamma aminobutyric acid (GABA) neurotransmitter signalling differentially sensitise Up and Down responder GBM models to standard treatment in vitro.

cancer biology↗