Polarizing receptor activation dissociates Fibroblast Growth Factor 2 mediated inhibition of myelination from its neuroprotective potential

Fibroblast growth factor (FGF) signaling contributes to failure of remyelination in multiple sclerosis, but targeting this therapeutically is complicated by its functional pleiotropy. We now identify FGF2 as a factor up-regulated by astrocytes in active inflammatory lesions that disrupts myelination via FGF receptor 2 (FGFR2) mediated activation of Wingless (Wnt) signaling; pharmacological inhibition of Wnt being sufficient to abrogate inhibition of myelination by FGF2 in tissue culture. Using a novel FGFR1-selective agonist (F2 V2) generated by deleting the N-terminal 26 amino acids of FGF2 we demonstrate polarizing signal transduction to favor FGFR1 abrogates FGF mediated inhibition of myelination but retains its ability to induce expression of pro-myelinating and immunomodulatory factors that include Cd93, Lif, Il11, Hbegf, Cxcl1 and Timp1. Our data provide new insights into the mechanistic basis of remyelination failure in MS and identify selective activation of FGFR1 as a novel strategy to induce a neuroprotective signaling environment in multiple sclerosis and other neurological diseases

Кераміка «terra sigillata» з с. Зимне на Волині

Стаття присвячена публікації чотирьох керамічних посудин типу «terra sigillata», знайдених на дні р. Луги у с. Зимне Володимир-Волинського району Волинської області. Попередній аналіз цих знахідок дозволяє віднести їх до Понтійського центру виробництва такого посуду. Вірогідним шляхом потрапляння цієї колекції на Волинь була готська експансія у Північне Причорномор’я

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

Effect of Electrodeposition Reactor Type on Nickel Recovery from Electroplating Wastewater

AbstractNickel recovery from synthetic electroplating wastewater using electrodeposition reactor has been investigated. The experiment was conducted in batch system using two types of electrodeposition reactors, partitioned reactors using water hyacinth leaf and single chamber reactor, a copper plate cathode size, graphite anode and applied DC voltage of 5 V. The goal of this research was to obtain the best reactor type for nickel electrodeposition from NiSO4 solution. Factors analyzed in the study were the change in pH, conductivity, electric current, cathode mass and nickel concentration in the catholyte. The electrodeposition was carried out during 4 hours. The initial concentration of nickel in the catholyte contained 2,402.19 mg/L. The results showed that the partitioned reactor using of water hyacinth leaf performed better than the single chamber reactor. The partitioned reactor using water hyacinth leaf decreased concentration of nickel in catholyte to 1756.19 mg/L and had the current efficiency of 88.17% with the specific energy of 5.2 kwh/kg nickel

Testing the predictive capability of the Index of Connectivity (IC) on a 2022 debris-flow event considering the spatial variability of the forcing

Sediment connectivity is an important property of geomorphic systems reflecting the potential to route material through themselves and hence modulating the propagation of geomorphic changes. While the relevance of the concept is clear, connectivity cannot be measured directly and the discussion on the best methods to quantify connectivity is still ongoing. Probably the most frequently used approach is based on the index of connectivity (IC) as it was developed by Borselli et al. (2008) and later adapted by Cavalli et al. (2013) for alpine catchments. This index aims at quantifying the structural connectivity that is governed by the spatial configuration and properties of system components. Nevertheless, the predictive capabilities of this index for functional connectivity, i.e. the actual transfer of sediment between the system components, have not been conclusively validated with field data. Most importantly, previous studies have, to our knowledge, not taken into account the spatial variability of the hydrometeorological forcing that leads to different functional connectivity in locations with similar structural connectivity. In this study, we use a unique dataset to test the predictive capability of the IC for hillslope-channel coupling of debris flows in the Horlachtal, Austria (described by Rom et al., 2023). The dataset consists of aerial imagery and two airborne LiDAR digital elevation models from which n=156 debris flows were mapped and quantified that were triggered by intense rainstorms on July 20th and 23rd, 2022. For this event, adjusted radar data (INCA data from the Austrian meteorological survey, ZAMG, and measurements from weather stations within the study area) give a high-resolution account of the spatial distribution of rainfall intensities and sums. Using these data, each debris flow was characterised with respect to (i) the meteorological forcing that affected its contributing area, (ii) morphometric properties of the latter, (iii) its sediment volume, and (iv) its runout length indicating functional connectivity, i.e. the degree of coupling to the main channel. Then we assessed the influence of structural connectivity (indicated by the IC) and hydrometeorological forcing on the observed functional connectivity. To our knowledge, this is the first study investigating the predictive capacity of the IC taking into account the spatial variability of the forcing. Among others, our results show that the IC is significantly higher for those debris flows that reached the main channel, compared to those that did not

Los fenoles del polen del g\ue9nero Zea

Se analizó la variabilidad de la composición fenólica del polen de 32 poblaciones de Zea mays subsp. mexicana, Zea mays subsp. parviglumis, Zea mays subsp. mays, Zea diploperennis, Zea perennis y Zea luxurians de México y Guatemala. Los perfiles se obtuvieron por cromatografía líquida de alta presión con detector de arreglo de diodos (HPLC-DAD) y cromatografía líquida de ultra resolución acoplada a espectrómetro de masas de tiempo de vuelo (UPLC-TOF-MS). Se encontró un total de 23 compuestos fenólicos (cuatro ácidos fenólicos, 16 flavonoles y tres dihidroflavonoides). Los derivados glicósidos de quercetina (siete derivados, además de la quercetina aglicona misma) fueron las substancias predominantes en todos los analisis realizados. El compuesto principal, el más abundante y presente en la totalidad de las muestras, incluido el maíz, se identificó como quercetina-3,3’-O-diglucósido. El polen de todas las especies y subespecies de Zea analizadas mostraron patrones muy similares de fenoles acumulados; sin embargo, diferencias en los compuestos menores (ácidos fenólicos y dihidroflavonoides) permitieron discernir variaciones inter e intraespecíficas, aunque la división del género en las dos secciones Luxuriantes y Zea no fue claramente sustentada. La baja variación de los perfiles fenólicos del polen dentro del género Zea apoya la propuesta de que el maíz y algunos teocintles son grupos conespecíficos, e indica que la composición fenólica del polen fue altamente conservada en los diferentes taxa de Zea a lo largo del tiempo