Notes

Look at Pre-malignant Wounds with the Uterine Cervix through Shear Influx Elastography: A whole new Analytic Application.
An understanding of adipocyte responsiveness to G-protein-coupled receptor-(GPCR) derived signals must take into consideration the role of membrane microenvironments; that individual sub-populations of proteins may vary significantly across different regions of the cell, and that cell differentiation alters those microenvironments. 3T3-L1 pre-adipocytes undergo a dramatic phenotypic transformation during differentiation into adipocytes, requiring the development of a transient primary cilium. We demonstrate that melanin-concentrating hormone (MCH) receptor 1, a GPCR that stimulates appetite, translocates to the transient primary cilium during early 3T3-L1 cell adipogenesis. Furthermore, we used RNA-Seq to investigate whether MCH signaling is influenced by its receptor localization and whether MCH can influence the transcriptome of early adipocyte development. We found that MCH signaling is sensitive to receptor localization to cilia, and this alters the adipogenic transcriptional program. Also, novel MCH signaling pathways in 3T3-L1 cells are identified, including those for circadian rhythm, the inflammatory response, and ciliary biogenesis. The presence of active MCH-signaling pathways in pre-adipocytes and the discovery that these pathways intersect with the early adipogenic program, among other newly-identified signaling pathways, suggests that the use of MCH receptor 1 antagonists for clinical interventions may have unintended consequences on adipose tissue development.The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented on MHC-I molecules. We demonstrated that the splicing inhibitor isoginkgetin and its water-soluble and non-toxic derivative IP2 act at the production stage of the pioneer translation products (PTPs). We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and impairs tumor growth in vivo. IP2 action is long-lasting and dependent on the CD8+ T cell response against TAs. We observed that the antigen repertoire displayed on MHC-I molecules at the surface of MCA205 fibrosarcoma is modified upon treatment with IP2. In particular, IP2 enhances the presentation of an exon-derived epitope from the tumor suppressor nischarin. The combination of IP2 with a peptide vaccine targeting the nischarin-derived epitope showed a synergistic antitumor effect in vivo. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.Locally advanced urothelial cancer has high recurrence and progression rates following surgical treatment. This highlights the need to develop neoadjuvant strategies that are both effective and well-tolerated. We hypothesized that neoadjuvant sub-ablative vascular-targeted photodynamic therapy (sbVTP), through its immunotherapeutic mechanism, would improve survival and reduce recurrence and progression in a murine model of urothelial cancer. After urothelial tumor implantation and 17 days before surgical resection, mice received neoadjuvant sbVTP (WST11; Tookad Soluble, Steba Biotech, France). Local and systemic response and survival served as measures of therapeutic efficacy, while immunohistochemistry and flow cytometry elucidated the immunotherapeutic mechanism. Data analysis included two-sided Kaplan-Meier, Mann-Whitney, and Fischer exact tests. Tumor volume was significantly smaller in sbVTP-treated animals than in controls (135 mm3 vs. 1222 mm3, P  less then  0.0001) on the day of surgery. Systemic progression was significantly lower in sbVTP-treated animals (l7% vs. 30%, P  less then  0.01). Both median progression-free survival and overall survival were significantly greater among animals that received sbVTP and surgery than among animals that received surgery alone (P  less then  0.05). Neoadjuvant-treated animals also demonstrated significantly lower local recurrence. Neoadjuvant sbVTP was associated with increased early antigen-presenting cells, and subsequent improvements in long-term memory and increases in effector and active T-cells in the spleen, lungs, and blood. In summary, neoadjuvant sbVTP delayed local and systemic progression, prolonged progression-free and overall survival, and reduced local recurrence, thereby demonstrating therapeutic efficacy through an immune-mediated response. These findings strongly support its evaluation in clinical trials.The use of wood panel residues as biomass for energy production is feasible. Heat treatments can improve energy properties while minimizing the emission of toxic gases due to thermoset polymers used in Medium Density Fiberboard (MDF) panels. Torrefaction or pre-carbonization, a heat treatment between 200 and 300 °C with low oxygen availability accumulates carbon and lignin, decreases hygroscopicity, and increases energy efficiency. The objective of this work was to evaluate the energy parameters (immediate, structural, and elementary chemical composition, moisture content, and yield) and density in torrefied MDF panels. The torrefaction improved the energetic features of coated MDF, decreasing the moisture content, volatile matter, and consequently, concentrating the carbon with better results in the samples torrefied for 40 min. The densitometric profiles of the torrefied MDF, obtained by X-ray densitometry, showed a decrease in the apparent density as torrefaction time increased. The digital X-ray images in gray and rainbow scale enabled the most detailed study of the density variation of MDF residues.Betweenness centrality quantifies the importance of a vertex for the information flow in a network. The standard betweenness centrality applies to static single-layer networks, but many real world networks are both dynamic and made of several layers. We propose a definition of betweenness centrality for temporal multiplexes. This definition accounts for the topological and temporal structure and for the duration of paths in the determination of the shortest paths. We propose an algorithm to compute the new metric using a mapping to a static graph. Camostat We apply the metric to a dataset of [Formula see text]k European flights and compare the results with those obtained with static or single-layer metrics. The differences in the airports rankings highlight the importance of considering the temporal multiplex structure and an appropriate distance metric.
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