Time and frequency domain methods for quantifying common modulation of motor unit firing patterns

BACKGROUND: In investigations of the human motor system, two approaches are generally employed toward the identification of common modulating drives from motor unit recordings. One is a frequency domain method and uses the coherence function to determine the degree of linear correlation between each frequency component of the signals. The other is a time domain method that has been developed to determine the strength of low frequency common modulations between motor unit spike trains, often referred to in the literature as 'common drive'. METHODS: The relationships between these methods are systematically explored using both mathematical and experimental procedures. A mathematical derivation is presented that shows the theoretical relationship between both time and frequency domain techniques. Multiple recordings from concurrent activities of pairs of motor units are studied and linear regressions are performed between time and frequency domain estimates (for different time domain window sizes) to assess their equivalence. RESULTS: Analytically, it may be demonstrated that under the theoretical condition of a narrowband point frequency, the two relations are equivalent. However practical situations deviate from this ideal condition. The correlation between the two techniques varies with time domain moving average window length and for window lengths of 200 ms, 400 ms and 800 ms, the r(2 )regression statistics (p < 0.05) are 0.56, 0.81 and 0.80 respectively. CONCLUSIONS: Although theoretically equivalent and experimentally well correlated there are a number of minor discrepancies between the two techniques that are explored. The time domain technique is preferred for short data segments and is better able to quantify the strength of a broad band drive into a single index. The frequency domain measures are more encompassing, providing a complete description of all oscillatory inputs and are better suited to quantifying narrow ranges of descending input into a single index. In general the physiological question at hand should dictate which technique is best suited

Exploring Health-Promoting Attributes of Plant Proteins as a Functional Ingredient for the Food Sector : A Systematic Review of Human Interventional Studies

Peer reviewedPublisher PD

Concert recording 2022-11-11

[Track 1]: Sonata in C minor, HWV 366. I. Adagio ; [Track 2]: II. Bourrée / Georg Frideric Handel -- [Track 3]: Sonata in G Major. I. Andante / Giovanni Sammartini -- [Track 4 and 5]: Sonata in E minor Francesco Geminiani (1687–1762) -- [Track 6]: Sonata in A minor. I. Siciliana ; II. Sprirtuoso / Georg Phillipp Telemann -- [Track 7]: Trois pieces, Op. 31. II. Mélodie / Arthur Foote -- [Track 8]: Souvenir de Madrid / Pedro Soler -- [Track 9]: Concerto for oboe and strings. I. Pastorale / Ralph Vaughan Williams

Concert recording 2022-11-11

[Track 1]: Sonata in C minor, HWV 366. I. Adagio ; [Track 2]: II. Bourrée / Georg Frideric Handel -- [Track 3]: Sonata in G Major. I. Andante / Giovanni Sammartini -- [Track 4 and 5]: Sonata in E minor Francesco Geminiani (1687–1762) -- [Track 6]: Sonata in A minor. I. Siciliana ; II. Sprirtuoso / Georg Phillipp Telemann -- [Track 7]: Trois pieces, Op. 31. II. Mélodie / Arthur Foote -- [Track 8]: Souvenir de Madrid / Pedro Soler -- [Track 9]: Concerto for oboe and strings. I. Pastorale / Ralph Vaughan Williams

Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research

10.1371/journal.pone.0081234PLoS ONE812-POLN

Mediator Kinase Inhibition Further Activates Super-Enhancer Associated Genes in AML

Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors (TFs), and chromatin regulators, drive high expression of genes implicated in cell identity and disease, such as lineage-controlling TFs and oncogenes 1, 2. BRD4 and CDK7 are positive regulators of SE-mediated transcription3,4,5. In contrast, negative regulators of SE-associated genes have not been well described. Here we report that Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19 restrain increased activation of key SE-associated genes in acute myeloid leukaemia (AML) cells. We determined that the natural product cortistatin A (CA) selectively inhibited Mediator kinases, had antileukaemic activity in vitro and in vivo, and disproportionately induced upregulation of SE-associated genes in CA-sensitive AML cell lines but not in CA-insensitive cell lines. In AML cells, CA upregulated SE-associated genes with tumour suppressor and lineage-controlling functions, including the TFs CEBPA, IRF8, IRF1 and ETV6 6, 7, 8. The BRD4 inhibitor I-BET151 downregulated these SE-associated genes, yet also has antileukaemic activity. Individually increasing or decreasing expression of these TFs suppressed AML cell growth, providing evidence that leukaemia cells are sensitive to dosage of SE-associated genes. Our results demonstrate that Mediator kinases can negatively regulate SE-associated gene expression in specific cell types and can be pharmacologically targeted as a therapeutic approach to AML

Community forest management in Indonesia: Avoided deforestation in the context of anthropogenic and climate complexities

Community forest management has been identified as a win-win option for reducing deforestation while improving the welfare of rural communities in developing countries. Despite considerable investment in community forestry globally, systematic evaluations of the impact of these policies at appropriate scales are lacking. We assessed the extent to which deforestation has been avoided as a result of the Indonesian government’s community forestry scheme, Hutan Desa (Village Forest). We used annual data on deforestation rates between 2012 and 2016 from two rapidly developing islands: Sumatra and Kalimantan. The total area of Hutan Desa increased from 750 km2 in 2012 to 2500 km2 in 2016. We applied a spatial matching approach to account for biophysical variables affecting deforestation and Hutan Desa selection criteria. Performance was assessed relative to a counterfactual likelihood of deforestation in the absence of Hutan Desa tenure. We found that Hutan Desa management has successfully achieved avoided deforestation overall, but performance has been increasingly variable through time. Hutan Desa performance was influenced by anthropogenic and climatic factors, as well as land use history. Hutan Desa allocated on watershed protection forest or limited production forest typically led to a less avoided deforestation regardless of location. Conversely, Hutan Desa granted on permanent or convertible production forest had variable performance across different years and locations. The amount of rainfall during the dry season in any given year was an important climatic factor influencing performance. Extremely dry conditions during drought years pose additional challenges to Hutan Desa management, particularly on peatland, due to increased vulnerability to fire outbreaks. This study demonstrates how the performance of Hutan Desa in avoiding deforestation is fundamentally affected by biophysical and anthropogenic circumstances over time and space. Our study improves understanding on where and when the policy is most effective with respect to deforestation, and helps identify opportunities to improve policy implementation. This provides an important first step towards evaluating the overall effectiveness of this policy in achieving both social and environmental goals

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