C16-Ceramide Analog Combined with Pc 4 Photodynamic Therapy Evokes Enhanced Total Ceramide Accumulation, Promotion of DEVDase Activation in the Absence of Apoptosis, and Augmented Overall Cell Killing

Because of the failure of single modality approaches, combination therapy for cancer treatment is a promising alternative. Sphingolipid analogs, with or without anticancer drugs, can improve tumor response. C16-pyridinium ceramide analog LCL30, was used in combination with photodynamic therapy (PDT), an anticancer treatment modality, to test the hypothesis that the combined treatment will trigger changes in the sphingolipid profile and promote cell death. Using SCCVII mouse squamous carcinoma cells, and the silicone phthalocyanine Pc 4 for PDT, we showed that combining PDT with LCL30 (PDT/LCL30) was more effective than individual treatments in raising global ceramide levels, as well as in reducing dihydrosphingosine levels. Unlike LCL30, PDT, alone or combined, increased total dihydroceramide levels. Sphingosine levels were unaffected by LCL30, but were abolished after PDT or the combination. LCL30-triggered rise in sphingosine-1-phosphate was reversed post-PDT or the combination. DEVDase activation was evoked after PDT or LCL30, and was promoted post- PDT/LCL30. Neither mitochondrial depolarization nor apoptosis were observed after any of the treatments. Notably, treatment with the combination resulted in augmented overall cell killing. Our data demonstrate that treatment with PDT/LCL30 leads to enhanced global ceramide levels and DEVDase activation in the absence of apoptosis, and promotion of total cell killing

Naturally occurring diacetyl and 2,3-pentanedione concentrations associated with roasting and grinding unflavored coffee beans in a commercial setting

AbstractOver the last decade, concerns have been raised about potential respiratory health effects associated with occupational exposure to the flavoring additives diacetyl and 2,3-pentanedione. Both of these diketones are also natural components of many foods and beverages, including roasted coffee. To date, there are no published studies characterizing workplace exposures to these diketones during commercial roasting and grinding of unflavored coffee beans. In this study, we measured naturally occurring diacetyl, 2,3-pentanedione, and respirable dust at a facility that roasts and grinds coffee beans with no added flavoring agents. Sampling was conducted over the course of three roasting batches and three grinding batches at varying distances from a commercial roaster and grinder. The three batches consisted of lightly roasted soft beans, lightly roasted hard beans, and dark roasted hard beans. Roasting occurred for 37 to 41min, and the grinding process took between 8 and 11min. Diacetyl, 2,3-pentanedione, and respirable dust concentrations measured during roasting ranged from less than the limit of detection (<LOD) to 0.0039ppm, <LOD to 0.018ppm, and <LOD to 0.31mg/m3, respectively. During grinding, diacetyl, 2,3-pentanedione, and respirable dust concentrations ranged from 0.018 to 0.39ppm, 0.0089 to 0.21ppm, and <LOD to 1.7mg/m3, respectively. For any given bean/roast combination and sample location, diketone concentrations during grinding were higher than those measured during roasting. During grinding, concentrations decreased with increased distance from the source. Measured concentrations of both diketones were higher during grinding of soft beans than hard beans. The results indicate that airborne concentrations of naturally occurring diacetyl and 2,3-pentanedione associated with unflavored coffee processing: (1) are similar to the concentrations that have been measured in food flavoring facilities; (2) are likely to exceed some recommended short-term occupational exposure limits, but; (3) based on previous analyses of exposure response relationships in animal studies, are far below the concentrations that are expected to cause even minimal responses in the human respiratory tract

Plasma and Serum Proteins Bound to Nanoceria: Insights into Pathways by which Nanoceria May Exert Its Beneficial and Deleterious Effects \u3cem\u3eIn Vivo\u3c/em\u3e

Nanoceria (CeO2, cerium oxide nanoparticles) is proposed as a therapeutic for multiple disorders. In blood, nanoceria becomes protein-coated, changing its surface properties to yield a different presentation to cells. There is little information on the interaction of nanoceria with blood proteins. The current study is the first to report the proteomics identification of plasma and serum proteins adsorbed to nanoceria. The results identify a number of plasma and serum proteins interacting with nanoceria, proteins whose normal activities regulate numerous cell functions: antioxidant/detoxification, energy regulation, lipoproteins, signaling, complement, immune function, coagulation, iron homeostasis, proteolysis, inflammation, protein folding, protease inhibition, adhesion, protein/RNA degradation, and hormonal. The principal implications of this study are: 1) The protein corona may positively or negatively affect nanoceria cellular uptake, subsequent organ bioprocessing, and effects; and 2) Nanoceria adsorption may alter protein structure and function, including pro- and inflammatory effects. Consequently, prior to their use as therapeutic agents, better understanding of the effects of nanoceria protein coating is warranted

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

The Bolocam Galactic Plane Survey IV: 1.1 and 0.35 mm Dust Continuum Emission in the Galactic Center Region

The Bolocam Galactic Plane Survey (BGPS) data for a six square degree region of the Galactic plane containing the Galactic center is analyzed and compared to infrared and radio continuum data. The BGPS 1.1 mm emission consists of clumps interconnected by a network of fainter filaments surrounding cavities, a few of which are filled with diffuse near-IR emission indicating the presence of warm dust or with radio continuum characteristic of HII regions or supernova remnants. New 350 {\mu}m images of the environments of the two brightest regions, Sgr A and B, are presented. Sgr B2 is the brightest mm-emitting clump in the Central Molecular Zone and may be forming the closest analog to a super star cluster in the Galaxy. The Central Molecular Zone (CMZ) contains the highest concentration of mm and sub-mm emitting dense clumps in the Galaxy. Most 1.1 mm features at positive longitudes are seen in silhouette against the 3.6 to 24 {\mu}m background observed by the Spitzer Space Telescope. However, only a few clumps at negative longitudes are seen in absorption, confirming the hypothesis that positive longitude clumps in the CMZ tend to be on the near-side of the Galactic center, consistent with the suspected orientation of the central bar in our Galaxy. Some 1.1 mm cloud surfaces are seen in emission at 8 {\mu}m, presumably due to polycyclic aromatic hydrocarbons (PAHs). A ~0.2\degree (~30 pc) diameter cavity and infrared bubble between l \approx 0.0\degree and 0.2\degree surrounds the Arches and Quintuplet clusters and Sgr A. The bubble contains several clumpy dust filaments that point toward Sgr A\ast; its potential role in their formation is explored. [abstract truncated]Comment: 76 pages, 22 figures, published in ApJ: http://iopscience.iop.org/0004-637X/721/1/137

Deglacierization of a marginal basin and implications for outburst floods

This article was submitted to Cryospheric Sciences, a section of the journal Frontiers in Earth ScienceSuicide Basin is a partly glacierized marginal basin of Mendenhall Glacier, Alaska, that has released glacier lake outburst floods (GLOFs) annually since 2011. The floods cause inundation and erosion in the Mendenhall Valley, impacting homes and other infrastructure. Here, we utilize in-situ and remote sensing data to assess the recent evolution and current state of Suicide Basin. We focus on the 2018 and 2019 melt seasons, during which we collected most of our data, partly using unmanned aerial vehicles (UAVs). To provide longer-term context, we analyze DEMs collected since 2006 and model glacier surface mass balance over the 2006–2019 period. During the 2018 and 2019 outburst flood events, Suicide Basin released ∼ 30 Å~ 106 m3 of water within approximately 4–5 days. Since lake drainage was partial in both years, these ∼ 30 Å~ 106 m3 represent only a fraction (∼ 60%) of the basin’s total storage capacity. In contrast to previous years, subglacial drainage was preceded by supraglacial outflow over the ice dam, which lasted ∼ 1 day in 2018 and 6 days in 2019. Two large calving events occurred in 2018 and 2019, with submerged ice breaking off the main glacier during lake filling, thereby increasing the basin’s storage capacity. In 2018, the floating ice in the basin was 36 m thick on average. In 2019, ice thickness was 29 m, suggesting rapid decay of the ice tongue despite increasing ice inflow from Mendenhall Glacier. The ice dam at the basin entrance thinned by more than 5 m a–1 from 2018 to 2019, which is approximately double the rate of the reference period 2006–2018. While ice-dam thinning reduces water storage capacity in the basin, that capacity is increased by declining ice volume in the basin and longitudinal lake expansion, with the latter process challenging to predict. The potential for premature drainage onset (i.e., drainage before the lake’s storage capacity is reached), intermittent drainage decelerations, and early drainage termination further complicates prediction of future GLOF events.This work was funded by the Alaska Climate Adaptation Science Center (AK CASC). UAVs and other surveying equipment were partly funded through the U.S. National Science Foundation (NSF) award EAR-1921598. EH and SH were partially supported by the NSF award OIA-1753748 and the State of Alaska. Streamflow monitoring of the Mendenhall River and real-time imagery of Suicide Basin were funded by the U.S. Geological Survey Groundwater and Streamflow Information Program. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Ye

Characterization of organic aerosol across the global remote troposphere: A comparison of ATom measurements and global chemistry models

The spatial distribution and properties of submicron organic aerosol (OA) are among the key sources of uncertainty in our understanding of aerosol effects on climate. Uncertainties are particularly large over remote regions of the free troposphere and Southern Ocean, where very few data have been available and where OA predictions from AeroCom Phase II global models span 2 to 3 orders of magnitude, greatly exceeding the model spread over source regions. The (nearly) pole-to-pole vertical distribution of nonrefractory aerosols was measured with an aerosol mass spectrometer onboard the NASA DC-8 aircraft as part of the Atmospheric Tomography (ATom) mission during the Northern Hemisphere summer (August 2016) and winter (February 2017). This study presents the first extensive characterization of OA mass concentrations and their level of oxidation in the remote atmosphere. OA and sulfate are the major contributors by mass to submicron aerosols in the remote troposphere, together with sea salt in the marine boundary layer. Sulfate was dominant in the lower stratosphere. OA concentrations have a strong seasonal and zonal variability, with the highest levels measured in the lower troposphere in the summer and over the regions influenced by biomass burning from Africa (up to 10 μgsm-3). Lower concentrations (~ 0:1 0.3 μgsm-3) are observed in the northern middle and high latitudes and very low concentrations (< 0:1 μgsm-3) in the southern middle and high latitudes. The ATom dataset is used to evaluate predictions of eight current global chemistry models that implement a variety of commonly used representations of OA sources and chemistry, as well as of the AeroCom-II ensemble. The current model ensemble captures the average vertical and spatial distribution of measured OA concentrations, and the spread of the individual models remains within a factor of 5. These results are significantly improved over the AeroCom-II model ensemble, which shows large overestimations over these regions. However, some of the improved agreement with observations occurs for the wrong reasons, as models have the tendency to greatly overestimate the primary OA fraction and underestimate the sec-ondary fraction. Measured OA in the remote free troposphere is highly oxygenated, with organic aerosol to organic carbon (OA= OC) ratios of ~ 2.2 2.8, and is 30 % 60% more oxygenated than in current models, which can lead to significant errors in OA concentrations. The model measurement comparisons presented here support the concept of a more dynamic OA system as proposed by Hodzic et al. (2016), with enhanced removal of primary OA and a stronger production of secondary OA in global models needed to provide better agreement with observations. © 2020 IEEE Computer Society. All rights reserved

Chemical transport models often underestimate aerosol acidity in remote regions of the atmosphere

The inorganic fraction of fine particles affects numerous physicochemical processes in the atmosphere. However, there is large uncertainty in its burden and composition due to limited global measurements. Here, we present observations from eleven different aircraft campaigns from around the globe and investigate how aerosol pH and ammonium balance change from polluted to remote regions, such as over the oceans. Both parameters show increasing acidity with remoteness, at all altitudes, with pH decreasing from about 3 to about −1 and ammonium balance decreasing from almost 1 to nearly 0. We compare these observations against nine widely used chemical transport models and find that the simulations show more scatter (generally R2 \u3c 0.50) and typically predict less acidic aerosol in the most remote regions. These differences in observations and predictions are likely to result in underestimating the model-predicted direct radiative cooling effect for sulfate, nitrate, and ammonium aerosol by 15–39%