Is There a Causal Association between Genotoxicity and the Imposex Effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways

On the breaking of collinear factorization in QCD

We investigate the breakdown of collinear factorization for non-inclusive observables in hadron-hadron collisions. For pure QCD processes, factorization is violated at the three-loop level and it has a structure identical to that encountered previously in the case of super-leading logarithms. In particular, it is driven by the non-commutation of Coulomb/Glauber gluon exchanges with other soft exchanges. Beyond QCD, factorization may be violated at the two-loop level provided that the hard subprocess contains matrix element contributions with phase differences between different colour topologies.Comment: Version 2: minor improvements for journal publicatio

Conjugated polyelectrolyte nano field emission adlayers.

Here we report on a straightforward and rapid means of enhancing the field electron emission performance of nascent vertically aligned multi-walled carbon nanotubes by introducing a polar zwitterionic conjugated polyelectrolyte adlayer at the vacuum-emitter interface. We attribute the observed 66% decrease in turn-on electric field to the augmented emitter micro-morphology and shifted surface band structure. The composite emitters can be optically modulated by exploiting the absorption cross-section of the solution cast adlayer, which increases the local carrier concentration which broadens the effective electrostatic shape of the emitter during optical excitation. Assessment via scanning anode field emission microscopy reveals a 25% improvement in DC time stability, a significant reduction in long-term hysteresis shift, and a threefold increase in bandwidth during pulsed mode operation.Oppenheimer TrustThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/c6nh00071

Virus–Host Interactions Between Nonsecretors and Human Norovirus

BACKGROUND & AIMS: Human norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by the FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set of fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) express a limited array of HBGAs. Thus, nonsecretors have less diverse norovirus strain infections, including resistance to the epidemiologically dominant GII.4 strains. Because future human norovirus vaccines will comprise GII.4 antigen and because secretor phenotype impacts GII.4 infection and immunity, nonsecretors may mimic young children immunologically in response to GII.4 vaccination, providing a needed model to study crossprotection in the context of limited pre-exposure. METHODS: By using specimens collected from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus, we evaluated the breadth of serologic immunity by surrogate neutralization assays, and cellular activation and cytokine production by flow cytometry. RESULTS: GII.2 infection resulted in broad antibody and cellular immunity activation that persisted for at least 30 days for T cells, monocytes, and dendritic cells, and for 180 days for blocking antibody. Multiple cellular lineages expressing interferon-g and tumor necrosis factor-a dominated the response. Both T-cell and B-cell responses were cross-reactive with other GII strains, but not GI strains. To promote entry mechanisms, inclusion of bile acids was essential for GII.2 binding to nonsecretor HBGAs. CONCLUSIONS: These data support development of withingenogroup, cross-reactive antibody and T-cell immunity, key outcomes that may provide the foundation for eliciting broad immune responses after GII.4 vaccination in individuals with limited GII.4 immunity, including young children

CMIP5 Intermodel Relationships in the Baseline Southern Ocean Climate System and With Future Projections

This is the final version. Available on open access from Wiley via the DOI in this recordClimate models exhibit a broad range in the simulated properties of the climate system. In the early historical period, the absolute global mean surface air temperature in Coupled Model Intercomparison Project, phase 5 (CMIP5) models spans a range of ~12-15 °C. Other climate variables may be linked to global mean temperature, and so accurate representation of the baseline climate state is crucial for meaningful future climate projections. In CMIP5 baseline climate states, statistically significant intermodel correlations between Southern Ocean surface temperature, outgoing shortwave radiation, cloudiness, the position of the mid-latitude eddy-driven jet, and Antarctic sea ice area are found. The baseline temperature relationships extend to projected future changes in the same set of variables. The tendency for models with initially cooler Southern Ocean to exhibit more global warming, and vice versa for initially warmer models, is linked to baseline Southern Ocean climate system biases. Some of these intermodel correlations arise due to a ‘capacity for change’. For example, models with more sea ice initially have greater capacity to lose sea ice as the planet warms, whereas models with little sea ice initially are constrained in the amount they can lose. Similar constraints apply to Southern Ocean clouds, which are projected to reduce under radiative forcing, and the jet latitude, which is projected to migrate poleward. A first look at emerging data from CMIP6 reveals a shift of the relationship from the Southern Ocean towards the Antarctic region, possibly due to reductions in Southern Ocean biases, such westerly wind representation.Natural Environment Research Council (NERC)Centre for Southern Hemisphere Oceans ResearchAustralian Government National Environmental Science ProgramAustralian Research Council (ARC

Dinosaur peptides suggest mechanisms of protein survival

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival

Evidence for the existence of powder sub-populations in micronized materials : Aerodynamic size-fractions of aerosolized powders possess distinct physicochemical properties

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: To investigate the agglomeration behaviour of the fine ( 12.8 µm) particle fractions of salmeterol xinafoate (SX) and fluticasone propionate (FP) by isolating aerodynamic size fractions and characterising their physicochemical and re-dispersal properties. Methods: Aerodynamic fractionation was conducted using the Next Generation Impactor (NGI). Re-crystallized control particles, unfractionated and fractionated materials were characterized for particle size, morphology, crystallinity and surface energy. Re-dispersal of the particles was assessed using dry dispersion laser diffraction and NGI analysis. Results: Aerosolized SX and FP particles deposited in the NGI as agglomerates of consistent particle/agglomerate morphology. SX particles depositing on Stages 3 and 5 had higher total surface energy than unfractionated SX, with Stage 5 particles showing the greatest surface energy heterogeneity. FP fractions had comparable surface energy distributions and bulk crystallinity but differences in surface chemistry. SX fractions demonstrated higher bulk disorder than unfractionated and re-crystallized particles. Upon aerosolization, the fractions differed in their intrinsic emission and dispersion into a fine particle fraction (< 5.0 µm). Conclusions: Micronized powders consisted of sub-populations of particles displaying distinct physicochemical and powder dispersal properties compared to the unfractionated bulk material. This may have implications for the efficiency of inhaled drug deliveryPeer reviewe

Empirical Evaluation of Bone Extraction Protocols

The application of high-resolution analytical techniques to characterize ancient bone proteins requires clean, efficient extraction to obtain high quality data. Here, we evaluated many different protocols from the literature on ostrich cortical bone and moa cortical bone to evaluate their yield and relative purity using the identification of antibody-antigen complexes on enzyme-linked immunosorbent assay and gel electrophoresis. Moa bone provided an ancient comparison for the effectiveness of bone extraction protocols tested on ostrich bone. For the immunological part of this study, we focused on collagen I, osteocalcin, and hemoglobin because collagen and osteocalcin are the most abundant proteins in the mineralized extracellular matrix and hemoglobin is common in the vasculature. Most of these procedures demineralize the bone first, and then the remaining organics are chemically extracted. We found that the use of hydrochloric acid, rather than ethylenediaminetetraacetic acid, for demineralization resulted in the cleanest extractions because the acid was easily removed. In contrast, the use of ethylenediaminetetraacetic acid resulted in smearing upon electrophoretic separation, possibly indicating these samples were not as pure. The denaturing agents sodium dodecyl sulfate, urea, and guanidine HCl have been used extensively for the solubilization of proteins in non-biomineralized tissue, but only the latter has been used on bone. We show that all three denaturing agents are effective for extracting bone proteins. One additional method tested uses ammonium bicarbonate as a solubilizing buffer that is more appropriate for post-extraction analyses (e.g., proteomics) by removing the need for desalting. We found that both guanidine HCl and ammonium bicarbonate were effective for extracting many bone proteins, resulting in similar electrophoretic patterns. With the increasing use of proteomics, a new generation of scientists are now interested in the study of proteins from not only extant bone but also from ancient bone

Role of nickel in high rate methanol degradation in anaerobic granular sludge bioreactors

The effect of nickel deprivation from the influent of a mesophilic (30°C) methanol fed upflow anaerobic sludge bed (UASB) reactor was investigated by coupling the reactor performance to the evolution of the Methanosarcina population of the bioreactor sludge. The reactor was operated at pH 7.0 and an organic loading rate (OLR) of 5–15 g COD l−1 day−1 for 191 days. A clear limitation of the specific methanogenic activity (SMA) on methanol due to the absence of nickel was observed after 129 days of bioreactor operation: the SMA of the sludge in medium with the complete trace metal solution except nickel amounted to 1.164 (±0.167) g CH4-COD g VSS−1 day−1 compared to 2.027 (±0.111) g CH4-COD g VSS−1 day−1 in a medium with the complete (including nickel) trace metal solution. The methanol removal efficiency during these 129 days was 99%, no volatile fatty acid (VFA) accumulation was observed and the size of the Methanosarcina population increased compared to the seed sludge. Continuation of the UASB reactor operation with the nickel limited sludge lead to incomplete methanol removal, and thus methanol accumulation in the reactor effluent from day 142 onwards. This methanol accumulation subsequently induced an increase of the acetogenic activity in the UASB reactor on day 160. On day 165, 77% of the methanol fed to the system was converted to acetate and the Methanosarcina population size had substantially decreased. Inclusion of 0.5 μM Ni (dosed as NiCl2) to the influent from day 165 onwards lead to the recovery of the methanol removal efficiency to 99% without VFA accumulation within 2 days of bioreactor operation

Influence of Microbial Biofilms on the Preservation of Primary Soft Tissue in Fossil and Extant Archosaurs

Background: Mineralized and permineralized bone is the most common form of fossilization in the vertebrate record. Preservation of gross soft tissues is extremely rare, but recent studies have suggested that primary soft tissues and biomolecules are more commonly preserved within preserved bones than had been presumed. Some of these claims have been challenged, with presentation of evidence suggesting that some of the structures are microbial artifacts, not primary soft tissues. The identification of biomolecules in fossil vertebrate extracts from a specimen of Brachylophosaurus canadensis has shown the interpretation of preserved organic remains as microbial biofilm to be highly unlikely. These discussions also propose a variety of potential mechanisms that would permit the preservation of soft-tissues in vertebrate fossils over geologic time. Methodology/Principal Findings: This study experimentally examines the role of microbial biofilms in soft-tissue preservation in vertebrate fossils by quantitatively establishing the growth and morphology of biofilms on extant archosaur bone. These results are microscopically and morphologically compared with soft-tissue extracts from vertebrate fossils from the Hell Creek Formation of southeastern Montana (Latest Maastrichtian) in order to investigate the potential role of microbial biofilms on the preservation of fossil bone and bound organic matter in a variety of taphonomic settings. Base