Promising activities of marine natural products against hematopoietic malignancies

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially available marine-derived compounds for the treatment of various hematopoietic cancers (e.g., leukemia and lymphoma), two molecules in clinical trials, and series of compounds and/or extracts from marine micro-and macroorganisms which have shown promising properties. In addition, the mechanisms of action of several active compounds and extracts are still unknown and require further study. The continuous upgrading of omics technologies has also allowed identifying enzymes with possible bioactivity (e.g., L-asparaginase is currently used for the treatment of leukemia) or the enzymes involved in the synthesis of bioactive secondary metabolites which can be the target of heterologous expression and genetic engineering

Simulation of the Earth's radio leakage from mobile towers as seen from selected nearby stellar systems

Mobile communication towers represent a relatively new but growing contributor to the total radio leakage associated with planet Earth. We investigate the overall power contribution of mobile communication towers to the Earth\'s radio leakage budget, as seen from a selection of different nearby stellar systems. We created a model of this leakage using publicly available data of mobile tower locations. The model grids the planet's surface into small, computationally manageable regions, assuming a simple integrated transmission pattern for the mobile antennas. In this model, these mobile tower regions rise and set as the Earth rotates. In this way, a dynamic power spectrum of the Earth was determined, summed over all cellular frequency bands. We calculated this dynamic power spectrum from three different viewing points, HD 95735, Barnard star, and Alpha Centauri A. Our preliminary results demonstrate that the peak power leaking into space from mobile towers is $\sim 4$GW. This is associated with LTE mobile tower technology emanating from the East Coast of China as viewed from HD 95735. We demonstrate that the mobile tower leakage is periodic, direction dependent, and could not currently be detected by a nearby civilization located within 10 light years of the Earth, using instrumentation with a sensitivity similar to the Green Bank Telescope. We plan to extend our model to include more powerful 5G mobile systems, radar installations, ground based uplinks (including the Deep Space Network), and various types of satellite services, including low Earth orbit constellations such as Starlink and OneWeb

5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-b-synthase in colon cancer cells lacking p53

Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53

Salmonella Contamination of Swine Carcasses and Pork Products

This paper includes results from two separate studies: one surveyed the level of contamination at four points during the slaughter and processing of chilled pork; the second study surveyed ground pork from 17 companies representing five different segments of ground pork distribution. Regarding the carcass study, the highest percentage of Salmonella spp. isolated from the different sampling sites by a swab method, for both pork loin and ham surfaces, was 4.4% after the singeing step of the slaughter process. Overall, 1.7% of all pork samples showing positive isolations for Salmonella spp., however, there were no Salmonella spp. found in one of the three plants surveyed. Salmonella were isolated primarily from pork before fabrication and refrigerated storage. A continous reduction in the numbers of Salmonella spp. isolates was detected from the point of singeing to the point of fabrication. No Salmonella spp. were isolated from vacuumpackaged pork stored for 36 days at 2EC. The purpose of the ground pork project was to survey current sources of ground pork, and to determine the effects of different handling methods and raw material sources on the microbial quality of ground pork. There were no significant differences in the microbial counts, or prevalence of selected organisms, between the different types of companies from which the ground pork was obtained. Estimated variance among locations, samples and sample duplicates show that additional ground pork samples are needed to strengthen the results of this study

Atmospheric black carbon and warming effects influenced by the source and absorption enhancement in central Europe

Particles containing black carbon (BC), a strong absorbing substance, exert a rather uncertain direct and indirect radiative forcing in the atmosphere. To investigate the mass concentration and absorption properties of BC particles over central Europe, the model WRF-Chem was used at a resolution of 12 km in conjunction with a high-resolution BC emission inventory (EUCAARI 42-Pan-European Carbonaceous Aerosol Inventory; 1/8° × 1/16°). The model simulation was evaluated using measurements of equivalent soot carbon, absorption coefficients and particle number concentrations at seven sites within the German Ultrafine Aerosol Network, PM mass concentrations from the dense measurement network of the German Federal Environmental Agency at 392 monitoring stations, and aerosol optical depth from MODIS and AERONET. A distinct time period (25 March to 10 April 2009) was chosen, during which the clean marine air mass prevailed in the first week and afterwards the polluted continental air mass mainly from the southeast dominated with elevated daily average BC concentration of up to 4 μ g m−3. The simulated PM mass concentration, aerosol number concentration and optical depth were in good agreement with the observations, while the modelled BC mass concentrations were found to be a factor of 2 lower than the observations. Together with back trajectories, detailed model bias analyses suggested that the current BC emission in countries to the east and south of Germany might be underestimated by a factor of 5, at least for the simulation period. Running the model with upscaled BC emissions in these regions led to a smaller model bias and a better correlation between model and measurement. In contrast, the particle absorption coefficient was positively biased by about 20% even when the BC mass concentration was underestimated by around 50%. This indicates that the internal mixture treatment of BC in the WRF-Chem optical calculation is unrealistic in our case, which overamplifies the light absorption by BC-containing particles. By adjusting the modelled mass absorption cross-section towards the measured values, the simulation of particle light absorption of BC was improved as well. Finally, the positive direct radiative forcing of BC particles at the top of the atmosphere was estimated to be in the range of 0 to +4 W m−2 over Germany for the model run with improved BC mass concentration and adjusted BC light absorption cross-section. This adjustment lowered the positive forcing of BC by up to 70%, compared with the internal mixing treatment of BC in the model simulation

Time-dependent entrainment of smoke presents an observational challenge for assessing aerosol–cloud interactions over the southeast Atlantic Ocean

The colocation of clouds and smoke over the southeast Atlantic Ocean during the southern African biomass burning season has numerous radiative implications, including microphysical modulation of the clouds if smoke is entrained into the marine boundary layer. NASA's ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) campaign is studying this system with aircraft in three field deployments between 2016 and 2018. Results from ORACLES-2016 show that the relationship between cloud droplet number concentration and smoke below cloud is consistent with previously reported values, whereas cloud droplet number concentration is only weakly associated with smoke immediately above cloud at the time of observation. By combining field observations, regional chemistry–climate modeling, and theoretical boundary layer aerosol budget equations, we show that the history of smoke entrainment (which has a characteristic mixing timescale on the order of days) helps explain variations in cloud properties for similar instantaneous above-cloud smoke environments. Precipitation processes can obscure the relationship between above-cloud smoke and cloud properties in parts of the southeast Atlantic, but marine boundary layer carbon monoxide concentrations for two case study flights suggest that smoke entrainment history drove the observed differences in cloud properties for those days. A Lagrangian framework following the clouds and accounting for the history of smoke entrainment and precipitation is likely necessary for quantitatively studying this system; an Eulerian framework (e.g., instantaneous correlation of A-train satellite observations) is unlikely to capture the true extent of smoke–cloud interaction in the southeast Atlantic.</p

Designing effective control of dengue with combined interventions

Viruses transmitted by Aedes mosquitoes, such as dengue, Zika, and chikungunya, have expanding ranges and seem unabated by current vector control programs. Effective control of these pathogens likely requires integrated approaches. We evaluated dengue management options in an endemic setting that combine novel vector control and vaccination using an agent-based model for Yucatán, Mexico, fit to 37 y of data. Our intervention models are informed by targeted indoor residual spraying (TIRS) experiments; trial outcomes and World Health Organization (WHO) testing guidance for the only licensed dengue vaccine, CYD-TDV; and preliminary results for in-development vaccines. We evaluated several implementation options, including varying coverage levels; staggered introductions; and a one-time, large-scale vaccination campaign. We found that CYD-TDV and TIRS interfere: while the combination outperforms either alone, performance is lower than estimated from their separate benefits. The conventional model hypothesized for in-development vaccines, however, performs synergistically with TIRS, amplifying effectiveness well beyond their independent impacts. If the preliminary performance by either of the in-development vaccines is upheld, a one-time, large-scale campaign followed by routine vaccination alongside aggressive new vector control could enable short-term elimination, with nearly all cases avoided for a decade despite continuous dengue reintroductions. If elimination is impracticable due to resource limitations, less ambitious implementations of this combination still produce amplified, longer-lasting effectiveness over single-approach interventions

Social assessment on an integrated intervention for the prevention of Zika and other Aedes-borne diseases in pregnant women and their families in Mexico

Results of the project show that pregnant women can be provided with free or low-cost integrated interventions with methods of known efficacy (topical repellent and insecticide-treated window screens) along with educative strategies, and that they are highly motivated to use these methods to enhance maternal-child health for Zika and other Aedes-borne diseases (ABD). This is a one-page assessment/synopsis of the integrated intervention

Use of lidar aerosol extinction and backscatter coefficients to estimate cloud condensation nuclei (CCN) concentrations in the southeast Atlantic

Accurately capturing cloud condensation nuclei (CCN) concentrations is key to understanding the aerosol–cloud interactions that continue to feature the highest uncertainty amongst numerous climate forcings. In situ CCN observations are sparse, and most non-polarimetric passive remote sensing techniques are limited to providing column-effective CCN proxies such as total aerosol optical depth (AOD). Lidar measurements, on the other hand, resolve profiles of aerosol extinction and/or backscatter coefficients that are better suited for constraining vertically resolved aerosol optical and microphysical properties. Here we present relationships between aerosol backscatter and extinction coefficients measured by the airborne High Spectral Resolution Lidar 2 (HSRL-2) and in situ measurements of CCN concentrations. The data were obtained during three deployments in the NASA ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) project, which took place over the southeast Atlantic (SEA) during September 2016, August 2017, and September–October 2018. Our analysis of spatiotemporally collocated in situ CCN concentrations and HSRL-2 measurements indicates strong linear relationships between both data sets. The correlation is strongest for supersaturations (S) greater than 0.25 % and dry ambient conditions above the stratocumulus deck, where relative humidity (RH) is less than 50 %. We find CCN–HSRL-2 Pearson correlation coefficients between 0.95–0.97 for different parts of the seasonal burning cycle that suggest fundamental similarities in biomass burning aerosol (BBA) microphysical properties. We find that ORACLES campaign-average values of in situ CCN and in situ extinction coefficients are qualitatively similar to those from other regions and aerosol types, demonstrating overall representativeness of our data set. We compute CCN–backscatter and CCN–extinction regressions that can be used to resolve vertical CCN concentrations across entire above-cloud lidar curtains. These lidar-derived CCN concentrations can be used to evaluate model performance, which we illustrate using an example CCN concentration curtain from the Weather Research and Forecasting Model coupled with physics packages from the Community Atmosphere Model version 5 (WRF-CAM5). These results demonstrate the utility of deriving vertically resolved CCN concentrations from lidar observations to expand the spatiotemporal coverage of limited or unavailable in situ observations.</p