Community air pollution and mortality: Analysis of 1980 data from US metropolitan areas. 1: Particulate air pollution

1980 data from up to 149 metropolitan areas were used to define cross-sectional associations between community air pollution and excess human mortality. The regression model proposed by Oezkaynak and Thurston, which accounted for age, race, education, poverty, and population density, was evaluated and several new models were developed. The new models also accounted for population change, drinking water hardness, and smoking, and included a more detailed description of race. Cause-of-death categories analyzed include all causes, all non-external causes, major cardiovascular diseases, and chronic obstructive pulmonary diseases (COPD). Both annual mortality rates and their logarithms were analyzed. The data on particulates were averaged across all monitoring stations available for each SMSA and the TSP data were restricted to the year 1980. The associations between mortality and air pollution were found to be dependent on the socioeconomic factors included in the models, the specific locations included din the data set, and the type of statistical model used. Statistically significant associations were found between TSP and mortality due to non-external causes with log-linear models, but not with a linear model, and between TS and COPD mortality for both linear and log-linear models. When the sulfate contribution to TSP was subtracted, the relationship with COPD mortality was strengthened. Scatter plots and quintile analyses suggested a TSP threshold for COPD mortality at around 65 ug/m{sup 3} (annual average). SO{sub 4}{sup {minus}2}, Mn, PM{sup 15}, and PM{sub 2.5} were not significantly associated with mortality using the new models

Metropolitan New York in the greenhouse: Air quality and health effects

A variety of potential effects on human health resulting from climate change have been identified in several assessments. According to an international panel{sup 1} they include direct effects of extreme temperatures on cardiovascular deaths, secondary effects due to vector-borne diseases or crop yields, and tertiary effects such as those that might arise from conflicts over freshwater supplies. To this fist we add the secondary effects of increased air pollution, which may result either directly from climate change or indirectly from increased air conditioning loads and the corresponding pollutant emissions from electric utilities. Higher ozone concentrations have been linked to increased ambient temperatures by both theory and observations of monitoring data. A similar association with particulate matter has been limited to observations, thus far. The pollution-heat linkage has been recognized before` but health effects have not been evaluated in terms of predictions of the joint effects of both agents. This paper has been prepared in two sections. First, we discuss the ozone situation with special reference to the Northeast Corridor and New York. In the second section, we present estimates of the health effects of climate change on New York and discuss some mitigation options

Influence of Ibuprofen on Phospholipid Membranes

Basic understanding of biological membranes is of paramount importance as these membranes comprise the very building blocks of life itself. Cells depend in their function on a range of properties of the membrane, which are important for the stability and function of the cell, information and nutrient transport, waste disposal and finally the admission of drugs into the cell and also the deflection of bacteria and viruses. We have investigated the influence of ibuprofen on the structure and dynamics of L-alpha-phosphatidylcholine (SoyPC) membranes by means of grazing incidence small-angle neutron scattering (GISANS), neutron reflectometry and grazing incidence neutron spin echo spectroscopy (GINSES). From the results of these experiments we were able to determine that ibuprofen induces a two-step structuring behavior in the SoyPC films, where the structure evolves from the purely lamellar phase for pure SoyPC over a superposition of two hexagonal phases to a purely hexago- nal phase at high concentrations. Additionally, introduction of ibuprofen stiffens the membranes. This behavior may be instrumental in explaining the toxic behavior of ibuprofen in long-term application.Comment: -Improved indexing in Fig. 4e) -changed concentrations to mol% -improved arguments, however conclusions stay unchange

Stretching and Heating Single DNA Molecules with Optically Trapped Gold-Silica Janus Particles

Self-propelled micro- and nanoscale motors are capable of autonomous motion typically by inducing local concentration gradients or thermal gradients in their surrounding medium. This is a result of the heterogeneous surface of the self-propelled structures that consist of materials with different chemical or physical properties. Here we present a self-thermophoretically driven Au–silica Janus particle that can simultaneously stretch and partially melt a single double-stranded DNA molecule. We show that the effective force acting on the DNA molecule is in the ∼pN range, well suited to probe the entropic stretching regime of DNA, and we demonstrate that the local temperature enhancement around the gold side of the particle produces partial DNA dehybridization

Quantifying epigenetic modulation of nucleosome breathing by high-throughput AFM imaging

Nucleosomes are the basic units of chromatin and critical for storage and expression of eukaryotic genomes. Chromatin accessibility and gene readout are heavily regulated by epigenetic marks, in which post-translational modifications of histones play a key role. However, the mode of action and the structural implications at the single-molecule level of nucleosomes is still poorly understood. Here we apply a high-throughput atomic force microscopy imaging and analysis pipeline to investigate the conformational landscape of the nucleosome variants three additional methyl groups at lysine 36 of histone H3 (H3K36me3), phosphorylation of H3 histones at serine 10 (H3S10phos), and acetylation of H4 histones at lysines 5, 8, 12, and 16 (H4K5/8/12/16ac). Our data set of more than 25,000 nucleosomes reveals nucleosomal unwrapping steps corresponding to 5-bp DNA. We find that H3K36me3 nucleosomes unwrap significantly more than wild-type nucleosomes and additionally unwrap stochastically from both sides, similar to centromere protein A (CENP-A) nucleosomes and in contrast to the highly anticooperative unwrapping of wild-type nucleosomes. Nucleosomes with H3S10phos or H4K5/8/12/16ac modifications show unwrapping populations similar to wild-type nucleosomes and also retain the same level of anticooperativity. Our findings help to put the mode of action of these modifications into context. Although H3K36me3 likely acts partially by directly affecting nucleosome structure on the single-molecule level, H3S10phos and H4K5/8/12/16ac must predominantly act through higher-order processes. Our analysis pipeline is readily applicable to other nucleosome variants and will facilitate future high-resolution studies of the conformational landscape of nucleoprotein complexes

High-throughput AFM analysis reveals unwrapping pathways of H3 and CENP-A nucleosomes

Nucleosomes, the fundamental units of chromatin, regulate readout and expression of eukaryotic genomes. Single-molecule experiments have revealed force-induced nucleosome accessibility, but a high-resolution unwrapping landscape in the absence of external forces is currently lacking. Here, we introduce a high-throughput pipeline for the analysis of nucleosome conformations based on atomic force microscopy and automated, multi-parameter image analysis. Our data set of ∼10 000 nucleosomes reveals multiple unwrapping states corresponding to steps of 5 bp DNA. For canonical H3 nucleosomes, we observe that dissociation from one side impedes unwrapping from the other side, but in contrast to force-induced unwrapping, we find only a weak sequence-dependent asymmetry. Notably, centromeric CENP-A nucleosomes do not unwrap anti-cooperatively, in stark contrast to H3 nucleosomes. Finally, our results reconcile previous conflicting findings about the differences in height between H3 and CENP-A nucleosomes. We expect our approach to enable critical insights into epigenetic regulation of nucleosome structure and stability and to facilitate future high-throughput AFM studies that involve heterogeneous nucleoprotein complexes

The free energy landscape of retroviral integration

Retroviral integration, the process of covalently inserting viral DNA into the host genome, is a point of no return in the replication cycle. Yet, strand transfer is intrinsically iso-energetic and it is not clear how efficient integration can be achieved. Here we investigate the dynamics of strand transfer and demonstrate that consecutive nucleoprotein intermediates interacting with a supercoiled target are increasingly stable, resulting in a net forward rate. Multivalent target interactions at discrete auxiliary interfaces render target capture irreversible, while allowing dynamic site selection. Active site binding is transient but rapidly results in strand transfer, which in turn rearranges and stabilizes the intasome in an allosteric manner. We find the resulting strand transfer complex to be mechanically stable and extremely long-lived, suggesting that a resolving agent is required in vivo

Different Secondary Metabolite Profiles of Phylogenetically almost Identical Streptomyces griseus Strains Originating from Geographically Remote Locations

As Streptomyces have shown an outstanding capacity for drug production, different campaigns in geographically distant locations currently aim to isolate new antibiotic producers. However, many of these newly isolated Streptomyces strains are classified as identical to already described species. Nevertheless, as discrepancies in terms of secondary metabolites and morphology are possible, we compared two Streptomyces strains with identical 16S rRNA gene sequences but geographically distant origins. Chosen were an Easter Island Streptomyces isolate (Streptomyces sp. SN25_8.1) and the next related type strain, which is Streptomyces griseus subsp. griseus DSM 40236T isolated from Russian garden soil. Compared traits included phylogenetic relatedness based on 16S rRNA gene sequences, macro and microscopic morphology, antibiotic activity and secondary metabolite profiles. Both Streptomyces strains shared several common features, such as morphology and core secondary metabolite production. They revealed differences in pigmentation and in the production of accessory secondary metabolites which appear to be strain-specific. In conclusion, despite identical 16S rRNA classification Streptomyces strains can present different secondary metabolite profiles and may well be valuable for consideration in processes for drug discover