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Keeping the balance: the noncoding RNA 7SK as a master regulator for neuron development and function
(2021)
The noncoding RNA 7SK is a critical regulator of transcription by adjusting the activity of the kinase complex P-TEFb. Release of P-TEFb from 7SK stimulates transcription at many genes by promoting productive elongation. Conversely, P-TEFb sequestration by 7SK inhibits transcription. Recent studies have shown that 7SK functions are particularly important for neuron development and maintenance and it can thus be hypothesized that 7SK is at the center of many signaling pathways contributing to neuron function. 7SK activates neuronal gene expression programs that are key for terminal differentiation of neurons. Proteomics studies revealed a complex protein interactome of 7SK that includes several RNA-binding proteins. Some of these novel 7SK subcomplexes exert non-canonical cytosolic functions in neurons by regulating axonal mRNA transport and fine-tuning spliceosome production in response to transcription alterations. Thus, a picture emerges according to which 7SK acts as a multi-functional RNA scaffold that is integral for neuron homeostasis.
Fabrication of microchannels using 3D printing of sugars as fugitive material is explored in different fields, including microfluidics. However, establishing reproducible methods for the controlled production of sugar structures with sub-100 μm dimensions remains a challenge.
This study pioneers the processing of sugars by melt electrowriting (MEW) enabling the fabrication of structures with so far unprecedented resolution from Isomalt. Based on a systematic variation of process parameters, fibers with diameters down to 20 μm can be fabricated. The flexibility in the adjustment of fiber diameter by on-demand alteration of MEW parameters enables generating constructs with perfusable channels within polydimethylsiloxane molds. These channels have a diameter that can be adjusted from 30 to 200 μm in a single design.
Taken together, the experiments show that MEW strongly benefits from the thermal and physical stability of Isomalt, providing a robust platform for the fabrication of small-diameter embedded microchannel systems.
Despite TAVR emerging as the gold standard for a broad spectrum of patients, it is associated with serious complications. In this report we present a case, where a TAVR procedure led to a perforation at the aortomitral continuity, discuss the risk factors for the occurrence of perforations and how we decided to treat the patient.