Additional file 1 of Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density

Additional file 1 Figure S1. Phenotype of hGFAP-cre::lsl-Lin28A mice (GL) compared to hGFAP-cre control mice (CTRL). (a) Scheme of mouse breeding and the lsl-Lin28A transgene. Mice carrying the hGFAP-cre promotor are crossed with lsl-Lin28A mice carrying the CAGGS-loxP-PolyA-loxP-LIN28A(3x)-IRES-eGFP sequence. Cre mediated recombination of loxP sites results in removal of the PolyA-Sequence (functional “STOP”-sequence). Consequently, LIN28A is constitutively overexpressed in neural progenitor cells of hGFAP-cre::lsl-Lin28A (GL) mice. (b-q) Fatemapping analyses of hGFAP-positive cells targeted by Cre using hGFAP-cre::R26tdRFPfl/+ mouse brains. Control forebrain (lsl-R26tdRFPfl/+) at P15 with high power images of the hippocampus region (c), stratum pyramidale (d) and isocortex (e). In contrast of the control, hGFAP-cre::R26tdRFPfl/+ mice displayed RFP-positive cells within the forebrain (j-m) at P15. High power images of the hippocampus (k) stratum pyramidale (l) and isocortex (m) are shown. Control cerebellum (lsl-R26tdRFPfl/+) at P15 with high power images of the granule cell layer (g), cerebellar layering (molecular cell layer, purkinje cell layer and granule cell layer) (h) and white matter (i). In contrast of the control, hGFAP-cre::R26tdRFPfl/+ mice displayed RFP-positive cells within the cerebellum (n-q) at P15. High power images of the granule cell layer (o) cerebellar layering (molecular cell layer, purkinje cell layer and granule cell layer) (p) and white matter (q) are shown. GL mice displayed no significant differences in body appearance (r) and body weight (s). GL mice displayed no significant difference in brain macroscopy (t), brain weight (u) and cortical thickness (v). Kaplan Meier analyses showing decreased survival of GL mice compared to CTRL mice (p=0.0028, log-rank test, n=83 for CTRL, n=58 for GL) (w). Scale bar in b is 1000 µm for b and j; scale bar in c is 500 µm for c and k; scale bar in d is 50 µm for d and l; scale bar in e is 200 µm for e and m; scale bar in f is 250 µm for f and n; scale bar in g is 50 µm for g and o; scale bar in h is 100 µm for h and p; scale bar in l is 50 µm for l and q. CTRL n=15, GL n=12 for s, CTRL n=83, GL n=58 for t. FB = forebrain, CB = cerebellum. P values are shown in figures as ns= not significant (p>0.05), * p0.05), * p0.05), * p<0.05, ** p<0.01, *** p<0.001, **** p<0.000

Additional file 2 of Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density

Additional file 2 Supplementary Table 1

Video_1_Young COVID-19 Patients Show a Higher Degree of Microglial Activation When Compared to Controls.MP4

The severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) is the cause of human coronavirus disease 2019 (COVID-19). Since its identification in late 2019 SARS-CoV-2 has spread rapidly around the world creating a global pandemic. Although considered mainly a respiratory disease, COVID-19 also encompasses a variety of neuropsychiatric symptoms. How infection with SARS-CoV-2 leads to brain damage has remained largely elusive so far. In particular, it has remained unclear, whether signs of immune cell and / or innate immune and reactive astrogliosis are due to direct effects of the virus or may be an expression of a non-specific reaction of the brain to a severe life-threatening disease with a considerable proportion of patients requiring intensive care and invasive ventilation activation. Therefore, we designed a case-control-study of ten patients who died of COVID-19 and ten age-matched non-COVID-19-controls to quantitatively assess microglial and astroglial response. To minimize possible effects of severe systemic inflammation and / or invasive therapeutic measures we included only patients without any clinical or pathomorphological indication of sepsis and who had not been subjected to invasive intensive care treatment. Our results show a significantly higher degree of microglia activation in younger COVID-19 patients, while the difference was less and not significant for older COVID-19 patients. The difference in the degree of reactive gliosis increased with age but was not influenced by COVID-19. These preliminary data warrants further investigation of larger patient cohorts using additional immunohistochemical markers for different microglial phenotypes.</p