A kinematic analysis of hand configurations in static and dynamic fingerspelling

The focus of this study was the investigation of target handshapes in American Sign Language fingerspelling in order to determine whether there was a difference between static canonical structures and structures produced in the context of a movement sequence. This was achieved by measuring the joint angles of a signing hand with an 18-sensor CyberGlove® by Virtual Technologies, Inc. A discriminant analysis was used to identify targets that occurred at points of minimum angular joint velocity. A multivariate analysis of variance with planned compansons was then applied to these dynamic data along with the static data to test the hypothesis. The results showed that there was a significant difference between handshapes produced statically and those produced dynamically, which suggested that a simple, cipher model of static handshapes produced within the context of a movement sequence is not sufficient to account for the production and perception of fingerspelling. These findings may be applied to future research in sign language recognition, so that consideration of the variability of target handshapes, as influenced by the spatiotemporal environment, might be incorporated into future models

Depression, anxiety, and stress among hangover-sensitive and hangover-resistant drinkers

This study investigated potential differences in baseline (i.e., non-hangover-related) levels of depression, anxiety, and stress between individuals who are sensitive to and those resistant to hangovers after consuming alcohol. Participants included 5111 university students from the Netherlands and the U.K., including 3205 hangover-sensitive and 1906 hangover-resistant drinkers. All participants completed surveys on their demographics, alcohol consumption, and hangover susceptibility (whether they experienced a hangover in the past 12 months), as well as their baseline levels of depression, anxiety, and stress on the DASS-21 scale. The results showed that hangover-sensitive drinkers had significantly higher levels of anxiety and stress, but not depression, compared to hangover-resistant drinkers. However, the observed differences between the two groups were small, with a magnitude of less than 1 out of 42 points on the DASS-21 anxiety and stress subscales, and are thus unlikely to be clinically meaningful

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Systematic Identification of Single Amino Acid Variants in Glioma Stem-Cell-Derived Chromosome 19 Proteins

Novel proteoforms with single amino acid polymorphism represent proteins that often have altered biological functions but are less explored in the human proteome. We have developed an approach, searching high quality shotgun proteomic data against an extended protein database, to identify expressed mutant proteoforms in glioma stem cell (GSC) lines. The systematic search of MS/MS spectra has recognized 13 chromosome 19 proteins in GSCs with altered amino acid sequences using PEAKS 7.0 as the search engine. The results were further verified by manual spectral examination, validating 14 proteoforms. One of the novel findings, a mutant form of branched-chain aminoacyl transferase 2 (T186R), was verified at the transcript level and by SRM in several glioma stem cell lines. The structure of this proteoform examined by molecular modeling to estimate structural changes of mutation that could lead to functional modifications potentially linked to glioma. Based on our initial findings, we believe that our approach presented could contribute to construct a more complete map of the human functional proteome

Alberta Gambling Research Institute Conference 2021: Gambling in Canada: Current Research & Future Directions

Conference presentations and research posters presented at the event made available with the permission of the authors.The Alberta Gambling Research Institute's 20th Annual Conference "Gambling in Canada: Current Research & Future Directions" took place April 27-29, 2021 as a live virtual event. A selection of conference presentations and research posters presented at the event have been made available with the permission of the authors

Sequence Analysis of the Genome of Piscine Orthoreovirus (PRV) Associated with Heart and Skeletal Muscle Inflammation (HSMI) in Atlantic Salmon (Salmo salar)

Piscine orthoreovirus (PRV) is associated with heart- and skeletal muscle inflammation (HSMI) of farmed Atlantic salmon (Salmo salar). We have performed detailed sequence analysis of the PRV genome with focus on putative encoded proteins, compared with prototype strains from mammalian (MRV T3D)- and avian orthoreoviruses (ARV-138), and aquareovirus (GCRV-873). Amino acid identities were low for most gene segments but detailed sequence analysis showed that many protein motifs or key amino acid residues known to be central to protein function are conserved for most PRV proteins. For M-class proteins this included a proline residue in m2 which, for MRV, has been shown to play a key role in both the formation and structural organization of virus inclusion bodies, and affect interferon-b signaling and induction of myocarditis. Predicted structural similarities in the inner core-forming proteins l1 and s2 suggest a conserved core structure. In contrast, low amino acid identities in the predicted PRV surface proteins m1, s1 and s3 suggested differences regarding cellular interactions between the reovirus genera. However, for s1, amino acid residues central for MRV binding to sialic acids, and cleavage- and myristoylation sites in m1 required for endosomal membrane penetration during infection are partially or wholly conserved in the homologous PRV proteins. In PRV s3 the only conserved element found was a zinc finger motif. We provide evidence that the S1 segment encoding s3 also encodes a 124 aa (p13) protein, which appears to be localized to intracellular Golgi-like structures. The S2 and L2 gene segments are also potentially polycistronic, predicted to encode a 71 aa- (p8) and a 98 aa (p11) protein, respectively. It is concluded that PRV has more properties in common with orthoreoviruses than with aquareoviruses