Denver pain authenticity stimulus set (D-PASS).

We introduce the Denver Pain Authenticity Stimulus Set (D-PASS), a free resource containing 315 videos of 105 unique individuals expressing authentic and posed pain. All expressers were recorded displaying one authentic (105; pain was elicited via a pressure algometer) and two posed (210) expressions of pain (one posed expression recorded before [posed-unrehearsed] and one recorded after [posed-rehearsed] the authentic pain expression). In addition to authentic and posed pain videos, the database includes an accompanying codebook including metrics assessed at the expresser and video levels (e.g., Facial Action Coding System metrics for each video controlling for neutral images of the expresser), expressers' pain threshold and pain tolerance values, averaged pain detection performance by naïve perceivers who viewed the videos (e.g., accuracy, response bias), neutral images of each expresser, and face characteristic rating data for neutral images of each expresser (e.g., attractiveness, trustworthiness). The stimuli and accompanying codebook can be accessed for academic research purposes from https://digitalcommons.du.edu/lsdl_dpass/1/ . The relatively large number of stimuli allow for consideration of expresser-level variability in analyses and enable more advanced statistical approaches (e.g., signal detection analyses). Furthermore, the large number of Black (n = 41) and White (n = 56) expressers permits investigations into the role of race in pain expression, perception, and authenticity detection. Finally, the accompanying codebook may provide pilot data for novel investigations in the intergroup or pain sciences.

Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.

The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver.

In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers.

A growing body of evidence suggests that a loss of chromosome 9 open reading frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts and dipeptide-repeat proteins have already been examined thoroughly, much remains unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we performed a comprehensive RNA foci study in an extensive pathological cohort of C9ORF72 expansion carriers (n = 63). We evaluated two brain regions using a newly developed computer-automated pipeline allowing recognition of cell nuclei and RNA foci (sense and antisense) supplemented by manual counting. In the frontal cortex, the percentage of cells with sense or antisense RNA foci was 26 or 12%, respectively. In the cerebellum, 23% of granule cells contained sense RNA foci and 1% antisense RNA foci. Interestingly, the highest percentage of cells with RNA foci was observed in cerebellar Purkinje cells (~70%). In general, more cells contained sense RNA foci than antisense RNA foci; however, when antisense RNA foci were present, they were usually more abundant. We also observed that an increase in the percentage of cells with antisense RNA foci was associated with a delayed age at onset in the frontal cortex (r = 0.43, p = 0.003), whereas no other associations with clinico-pathological features were seen. Importantly, our large-scale study is the first to provide conclusive evidence that RNA foci are not the determining factor of the clinico-pathological variability observed in C9ORF72 expansion carriers and it emphasizes that the distribution of RNA foci does not follow the pattern of neurodegeneration, stressing the complex interplay between different aspects of C9ORF72-related diseases.