Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Acoustic emission monitoring from a lab scale high shear granulator - A novel approach

A new approach to the monitoring of granulation processes using passive acoustics together with precise control over the granulation process has highlighted the importance of particle-particle and particle-bowl collisions in acoustic emission. The results have shown that repeatable acoustic results could be obtained but only when a spray nozzle water addition system was used. Acoustic emissions were recorded from a transducer attached to the bowl and an airborne transducer. It was found that the airborne transducer detected very little from the granulation and only experienced small changes throughout the process. The results from the bowl transducer showed that during granulation the frequency content of the acoustic emission shifted towards the lower frequencies. Results from the discrete element model indicate that when larger particles are used the number of collisions the particles experience reduces. This is a result of the volume conservation methodology used in this study, therefore larger particles results in less particles. These simulation results coupled with previous theoretical work on the frequency content of an impacting sphere explain why the frequency content of the acoustic emissions reduces during granule growth. The acoustic system used was also clearly able to identify when large over-wetted granules were present in the system, highlighting its benefit for detecting undesirable operational conditions. High-speed photography was used to study if visual changes in the granule properties could be linked with the changing acoustic emissions. The high speed photography was only possible towards the latter stages of the granulation process and it was found that larger granules produced a higher magnitude of acoustic emission across a broader frequency range