A summer time series of particulate carbon in the air and snow at Summit, Greenland

Carbonaceous particulate matter is ubiquitous in the lower atmosphere, produced by natural and anthropogenic sources and transported to distant regions, including the pristine and climate-sensitive Greenland Ice Sheet. During the summer of 2006, ambient particulate carbonaceous compounds were characterized on the Greenland Ice Sheet, including the measurement of particulate organic (OC) and elemental (EC) carbon, particulate water-soluble organic carbon (WSOC), particulate absorption coefficient (σap), and particle size-resolved number concentration (PM0.1–1.0). Additionally, parallel ∼50-day time series of water-soluble organic carbon (WSOC), water-insoluble organic carbon (WIOC), and elemental carbon (EC) were quantified at time increments of 4–24 h in the surface snow. Measurement of atmospheric particulate carbon found WSOC (average of 52 ng m−3) to constitute a major fraction of particulate OC (average of 56 ng m−3), suggesting that atmospheric organic compounds reaching the Greenland Ice Sheet in summer are highly oxidized. Atmospheric EC (average of 7 ng m−3) was well-correlated with σap (r = 0.95) and the calculated mass-absorption cross-section (average of 24 m2 g−1) appears to be similar to that measured using identical techniques in an urban environment in the United States. Comparing surface snow to atmospheric particulate matter concentrations, it appears the snow has a much higher OC (WSOC+WIOC) to EC ratio (205:1) than air (10:1), suggesting that snow is additionally influenced by water-soluble gas-phase compounds. Finally, the higher-frequency (every 4–6 h) sampling of snow-phase WSOC revealed significant loss (40–54%) of related organic compounds in surface snow within 8 h of wet deposition

Particulate and water-soluble carbon measured in recent snow at Summit, Greenland

Water-soluble organic carbon (WSOC), waterinsoluble particulate organic carbon (WIOC), and particulate elemental carbon (EC) were measured simultaneously for the first time on the Greenland Ice Sheet in surface snow and in a 3-meter snow pit. Snow pit concentrations reveal that, on average, WSOC makes up the majority (89%) of carbonaceous species, followed by WIOC (10%) and EC (1%). The enhancement of OC relative to EC (ratio 99:1) in Greenland snow suggests that, along with atmospheric particulate matter, gaseous organics contribute to snow-phase OC. Comparison of summer surface snow concentrations in 2006 with past summer snow pit layers (2002 – 2005) found a significant depletion in WSOC (20 – 82%) and WIOC (46 – 65%) relative to EC for 3 of the 4 years. The apparent substantial loss of WSOC and WIOC in aged snow suggests that post-depositional processes, such as photochemical reactions, need to be considered in linking ice core records of organics to atmospheric concentrations. Citation: Hagler, G. S. W., M. H. Bergin, E. A. Smith, J. E. Dibb, C. Anderson, and E. J. Steig (2007), Particulate and water-soluble carbon measured in recent snow at Summit, Greenland, Geophys. Res. Lett., 34, L16505, doi:10.1029/2007GL030110

Regulation of B cell fate by chronic activity of the IgE B cell receptor.

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses

Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness.

UnlabelledWe analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a "commensal lifestyle." However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.ImportanceDuring critical illness, the normal gut microbiota becomes disrupted in response to host physiologic stress and antibiotic treatment. Here we demonstrate that the community structure of the gut microbiota during prolonged critical illness is dramatically changed such that in many cases only two-member pathogen communities remain. Most of these ultra-low-membership communities display low virulence when grouped together (i.e., a commensal lifestyle); individually, however, they can express highly harmful behaviors (i.e., a pathogenic lifestyle). The commensal lifestyle of the whole community can be shifted to a pathogenic one in response to host factors such as opioids that are released during physiologic stress and critical illness. This shift can be prevented by using compounds such as Pi-PEG15-20 that interrupt bacterial virulence expression. Taking the data together, this report characterizes the plasticity seen with respect to the choice between a commensal lifestyle and a pathogenic lifestyle among ultra-low-diversity pathogen communities that predominate in the gut during critical illness and offers novel strategies for prevention of sepsis

Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

Clustering in 18O - absolute determination of branching ratios via high-resolution particle spectroscopy

The determination of absolute branching ratios for high-energy states in light nuclei is an important and useful tool for probing the underlying nuclear structure of individual resonances: for example, in establishing the tendency of an excited state towards α -cluster structure. Difficulty arises in measuring these branching ratios due to similarities in available decay channels, such as ( 18 O, n ) and ( 18 O, 2 n ), as well as differences in geometric efficiencies due to population of bound excited levels in daughter nuclei. Methods are presented using Monte Carlo techniques to overcome these issues

Saliva from obese individuals suppresses the release of aroma compounds from wine.

BackgroundRecent evidence suggests that a lower extent of the retronasal aroma release correspond to a higher amount of ad libitum food intake. This has been regarded as one of the bases of behavioral choices towards food consumption in obese people. In this pilot study we investigated the hypothesis that saliva from obese individuals could be responsible for an alteration of the retro-nasal aroma release. We tested this hypothesis in vitro, by comparing the release of volatiles from a liquid food matrix (wine) after its interaction with saliva from 28 obese (O) and 28 normal-weight (N) individuals.Methods and findingsAmplicon sequencing of the 16S rRNA V4 region indicated that Firmicutes and Actinobacteria were more abundant in O, while Proteobacteria and Fusobacteria dominated in N. Streptococcaceae were significantly more abundant in the O subjects and constituted 34% and 19% on average of the saliva microbiota of O and N subjects, respectively. The Total Antioxidant Capacity was higher in O vs N saliva samples. A model mouth system was used to test whether the in-mouth wine aroma release differs after the interaction with O or N saliva. In O samples, a 18% to 60% significant decrease in the mean concentration of wine volatiles was detected as a result of interaction with saliva, compared with N. This suppression was linked to biochemical differences in O and N saliva composition, which include protein content.ConclusionMicrobiological and biochemical differences were found in O vs N saliva samples. An impaired retronasal aroma release from white wine was detected in vitro and linked to compositional differences between saliva from obese and normal-weight subjects. Additional in vivo investigations on diverse food matrices could contribute to understanding whether a lower olfactory stimulation due to saliva composition can be a co-factor in the development/maintenance of obesity

Microclimatic Performance of a Free-Air Warming and CO\u3csub\u3e2\u3c/sub\u3e Enrichment Experiment in Windy Wyoming, USA

In order to plan for global changing climate experiments are being conducted in many countries, but few have monitored the effects of the climate change treatments (warming, elevated CO2) on the experimental plot microclimate. During three years of an eight year study with year-round feedback-controlled infra-red heater warming (1.5/3.0°C day/night) and growing season free-air CO2 enrichment (600 ppm) in the mixed-grass prairie of Wyoming, USA, we monitored soil, leaf, canopy-air, above-canopy-air temperatures and relative humidity of control and treated experimental plots and evaluated ecologically important temperature differentials. Leaves were warmed somewhat less than the target settings (1.1 & 1.5°C day/night) but soil was warmed more creating an average that matched the target settings extremely well both during the day and night plus the summer and winter. The site typically has about 50% bare or litter covered soil, therefore soil heat transfer is more critical than in dense canopy ecosystems. The Wyoming site commonly has strong winds (5 ms-1 average) and significant daily and seasonal temperature fluctuations (as much as 30°C daily) but the warming system was nearly always able to maintain the set temperatures regardless of abiotic variation. The within canopy-air was only slightly warmed and above canopy- air was not warmed by the system, therefore convective warming was minor. Elevated CO2 had no direct effect nor interaction with the warming treatment on microclimate. Relative humidity within the plant canopy was only slightly reduced by warming. Soil water content was reduced by warming but increased by elevated CO2. This study demonstrates the importance of monitoring the microclimate in manipulative field global change experiments so that critical physiological and ecological conclusions can be determined. Highly variable energy demand fluctuations showed that passive IR heater warming systems will not maintain desired warming for much of the time

Pharmacodynamic differentiation of lorazepam sleepiness and dizziness using an ordered categorical measure

Categorical measures of lorazepam sleepiness and dizziness were modeled to identify differences in pharmacodynamic (PD) parameters between these adverse events (AEs). Differences in data-derived PD parameters were compared with relative incidence rates in the drug label (15.7% and 6.9%, respectively). Healthy volunteers ( n  = 20) received single oral doses of 2 mg lorazepam or placebo in a randomized, double-blind, cross-over fashion. A seven-point categorical scale measuring the intensity of AEs was serially administered over 24 h. The maximum score (MaxS), and area under the effect curve (AUEC) were determined by noncompartmental methods and compared using a paired t -test. Individual scores were modeled using a logistic function implemented in NONMEM. AUEC and MaxS for sleepiness were significantly higher than dizziness (20.35 vs. 9.76, p  < 0.01) and (2.35 vs. 1.45, p  < 0.01). Model slope estimates were similar for sleepiness and dizziness (0.21 logits × mL/ng vs. 0.19 logits × mL/ng), but baseline logits were significantly higher for sleepiness (−2.81 vs. −4.34 logits). Data-derived PD parameters were in concordance with label incidence rates. The higher intensity of sleepiness may be directly related to baseline (no drug present) while the increase in intensity as a result of drug was relatively similar for both AEs. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3628–3641, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77428/1/22093_ftp.pd