Summary
B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone of heat shock protein 90. Deletion of
Aip
in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma.
Time-lapse microscopy movies have transformed the study of subcellular dynamics. However, manual analysis of movies can introduce bias and variability, obscuring important insights. While automation can overcome such limitations, spatial and temporal discontinuities in time-lapse movies render methods such as 3D object segmentation and tracking difficult. Here, we present SpinX, a framework for reconstructing gaps between successive image frames by combining deep learning and mathematical object modeling. By incorporating expert feedback through selective annotations, SpinX identifies subcellular structures, despite confounding neighbor-cell information, non-uniform illumination, and variable fluorophore marker intensities. The automation and continuity introduced here allows the precise 3D tracking and analysis of spindle movements with respect to the cell cortex for the first time. We demonstrate the utility of SpinX using distinct spindle markers, cell lines, microscopes, and drug treatments. In summary, SpinX provides an exciting opportunity to study spindle dynamics in a sophisticated way, creating a framework for step changes in studies using time-lapse microscopy.
Purpose: Thyrotropin releasing hormone (TRH), a tripeptide hormone produced in the hypothalamus, controls thyroid stimulating hormone (TSH) production from the pituitary gland and hence the production of thyroid hormone. Extra-hypothalamic production and action of TRH has been detected, as has the presence of a C-terminal cyclised derivative, histidyl-proline diketopiperazine (His-Pro DKP). This study investigates the effects of these compounds on thyroglobulin release from thyroid follicular cells.
Methods: DKPs were identified by chromatography and mass spectrometry. Expression of RNAs and proteins were identified in the FTRL-5 thyroid cell line and supernatant using RT-qPCR and immunoblotting.
Results: We show that TRH is expressed by rat follicular thyroid cells, as is Pgpep1, the enzyme required for removal of the N-terminal amino acid of TRH. The rate of His-Pro DKP production from the C-terminal dipeptide of TRH is enhanced by thyroid extract in vitro. Both TRH and His-Pro DKP reduce thyroglobulin release from thyroid follicular cells with the magnitude of this effect attenuated in the presence of TSH, which also inhibits the expression of Pgpep1.
Conclusion: Collectively, these data indicate that TRH and its cyclised dipeptide derivative directly regulate thyroid production within the thyroid gland, potentially in a manner dependent upon the activity of the hypothalamic-pituitary-thyroid (HPT) axis. These findings provide further evidence that C-terminal peptide derivatives of classical hormones possess intrinsic biological activities.
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