Variability of aerosol, gaseous pollutants and meteorological characteristics associated with changes in air mass origin at the SW Atlantic coast of Iberia

Measurements of the ambient aerosol were performed at the Southern coast of Spain, within the framework of the DOMINO (<b>D</b>iel <b>O</b>xidant <b>M</b>echanisms <b>I</b>n relation to <b>N</b>itrogen <b>O</b>xides) project. The field campaign took place from 20 November until 9 December 2008 at the atmospheric research station "El Arenosillo" (37°5'47.76" N, 6°44'6.94" W). As the monitoring station is located at the interface between a natural park, industrial cities (Huelva, Seville) and the Atlantic Ocean, a variety of physical and chemical parameters of aerosols and gas phase could be characterized in dependency on the origin of air masses. Backwards trajectories were examined and compared with local meteorology to classify characteristic air mass types for several source regions. Aerosol number and mass as well as polycyclic aromatic hydrocarbons and black carbon concentrations were measured in PM<sub>1</sub> and size distributions were registered covering a size range from 7 nm up to 32 μm. The chemical composition of the non-refractory submicron aerosol (NR-PM<sub>1</sub>) was measured by means of an Aerosol Mass Spectrometer (Aerodyne HR-ToF-AMS). Gas phase analyzers monitored various trace gases (O<sub>3</sub>, SO<sub>2</sub>, NO, NO<sub>2</sub>, CO<sub>2</sub>) and a weather station provided meteorological parameters. <br><br> Lowest average submicron particle mass and number concentrations were found in air masses arriving from the Atlantic Ocean with values around 2 μg m<sup>−3</sup> and 1000 cm<sup>−3</sup>. These mass concentrations were about two to four times lower than the values recorded in air masses of continental and urban origins. For some species PM<sub>1</sub>-fractions in marine air were significantly larger than in air masses originating from Huelva, a closely located city with extensive industrial activities. The largest fraction of sulfate (54%) was detected in marine air masses and was to a high degree not neutralized. In addition, small concentrations of methanesulfonic acid (MSA), a product of biogenic dimethyl sulfate (DMS) emissions, could be identified in the particle phase. <br><br> In all air masses passing the continent the organic aerosol fraction dominated the total NR-PM<sub>1</sub>. For this reason, using Positive Matrix Factorization (PMF) four organic aerosol (OA) classes that can be associated with various aerosol sources and components were identified: a highly-oxygenated OA is the major component (43% OA) while semi-volatile OA accounts for 23%. A hydrocarbon-like OA mainly resulting from industries, traffic and shipping emissions as well as particles from wood burning emissions also contribute to total OA and depend on the air mass origin. <br><br> A significant variability of ozone was observed that depends on the impact of different air mass types and solar radiation

Meervoudige stress door herhaaldelijk gebruik van gewasbeschermingsmiddelen in landbouwgebieden

Current risk assessment of plant protection products is performed on a formulated-product-by-formulated-product basis and does not take into account the fact that products may be mixed and/or that different products are used sequentially within a growing season. This report evaluates three possibilities for taking these aspects into account in the future that target the risks for surface water. The investigated methods have been shown to be able to take 'multiple stresses' into consideration. Further investigation is needed to check if these methods are sufficient. In this report, three different methods were used to assess the multiple stresses caused by parallel and sequential applications of plant protection products according to realistic application scenarios during the growing season of a tuber crop and an orchard crop. The methods show the effects of the different products on the organisms living in a ditch at the edge of a field. The first method used is the so-called Toxic Unit method, in which the contributions of the individual substances to the overall toxicity are summed and the maximum in time is calculated. The second method, the mixture toxic pressure method (msPAF), calculates the potentially affected fraction of aquatic organisms, taking into account differences in the sensitivity of the organisms to the various substances. The third method, the MASTEP population model, calculates the time necessary for a sensitive aquatic organism (an aquatic isopod) to recover from its exposure to the various substances. The Toxic Unit method (TU) is the one most comparable to the current authorization assessment. All three methods show that a few substances determine a large part of the calculated total effect. The TU-method and the mixture toxic pressure (msPAF) method are useful in identifying these active substances. These selected substances were then used in the MASTEP calculations. The MASTEP method, using Asellus aquaticus as indicator species, did indicate no or hardly any longer recovery times for the multiple applications in comparison with those calculated for the individual pesticide applications. This result applies to species with a high number of offspring. It is recommended that the MASTEP method is used with water organisms that have other survival strategies. At the moment, EFSA (European Food Safety Authority) undertakes activities to develop tools and guidance to assess the human and ecological risks of combined exposure to multiple active substances. This report can contribute to these activities.In de huidige toelatingsbeoordeling van gewasbeschermingsmiddelen worden effecten beoordeeld op basis van de werkzame stoffen die er in zitten. Er wordt daarbij geen rekening mee gehouden dat er meerdere gewasbeschermingsmiddelen, met andere werkzame stoffen, bij dezelfde teelt worden gebruikt. Dit onderzoek verkent drie mogelijkheden om hier in de toekomst wel rekening mee te houden, gericht op de risico's voor oppervlaktewater. De onderzochte methoden blijken deze 'meervoudige stress' te kunnen meenemen. Wel is meer onderzoek nodig om na te gaan of deze methoden toereikend zijn. Voor dit onderzoek zijn met de drie methoden realistische scenario's van het gebruik van gewasbeschermingsmiddelen binnen een groeiseizoen voor een knolgewas en een fruitteeltgewas doorgerekend. De methoden nemen de effecten mee die de verschillende middelen hebben op de organismen in de nabijgelegen sloot. Een van de methoden telt toxiciteitsindexen bij elkaar op (de Toxic Unit-methode, TU), een andere houdt rekening met verschillen in gevoeligheid van soorten organismen voor het bestrijdingsmiddel (de toxisch druk-methode, msPAF) en de derde methode berekent effecten op en het herstel van een gevoelig waterorganisme (het MASTEP-populatiemodel voor de waterpissebed). De TU-methode is het meest vergelijkbaar met de huidige toelatingsbeoordeling. Bij alle drie de methoden blijkt dat enkele stoffen een groot deel van het totaal berekende effect bepalen. De TU-methode en de toxische druk- methode (msPAF) blijken nuttig om deze werkzame stoffen te bepalen. Met deze werkzame stoffen zijn vervolgens de MASTEP-berekeningen uitgevoerd. Uit de MASTEP-berekeningen blijkt dat de periode die de waterpissebed nodig heeft om te herstellen van het effect van de middelen niet of nauwelijks langer duurt als meerdere middelen tegelijk worden gebruikt. Dit resultaat geldt voor waterorganismen die als overlevingsstrategie hebben dat ze veel nakomelingen produceren. Het verdient aanbeveling de MASTEP- berekeningen ook uit te voeren voor organismen met andere overlevingsstrategieën. EFSA (European Food Safety Authority) zoekt momenteel naar mogelijkheden om richtlijnen en instrumenten te ontwikkelen voor het beoordelen van de risico's van gecombineerde blootstelling van mens en milieu aan meerdere werkzame stoffen. Dit rapport kan hieraan bijdragen.Ministerie van I&

Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases

\ua9 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.Stereoselective carbon-carbon bond forming reactions are quintessential transformations in organic synthesis. One example is the Diels-Alder reaction, a [4+2] cycloaddition between a conjugated diene and a dienophile to form cyclohexenes. The development of biocatalysts for this reaction is paramount for unlocking sustainable routes to a plethora of important molecules. To obtain a comprehensive understanding of naturally evolved [4+2] cyclases, and to identify hitherto uncharacterised biocatalysts for this reaction, we constructed a library comprising forty-five enzymes with reported or predicted [4+2] cycloaddition activity. Thirty-one library members were successfully produced in recombinant form. In vitro assays employing a synthetic substrate incorporating a diene and a dienophile revealed broad-ranging cycloaddition activity amongst these polypeptides. The hypothetical protein Cyc15 was found to catalyse an intramolecular cycloaddition to generate a novel spirotetronate. The crystal structure of this enzyme, along with docking studies, establishes the basis for stereoselectivity in Cyc15, as compared to other spirotetronate cyclases

The E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate cancer

BACKGROUND Research on castration resistant prostate cancer (CRPC) has focused primarily on functional alterations of the androgen receptor (AR). However, little is known about the loss of AR gene expression itself and the possible contribution of AR negative cells to CRPC. METHODS Human and murine prostate cancer tissue microarrays (TMAs) were evaluated with antibodies specific for E2F1, DNA methyltransferase 1 or AR. The human prostate cancer TMA consisted of clinical samples ranging from normal tissue to samples of metastatic disease. The murine TMA was comprised of benign, localized or metastatic prostate cancer acquired from TRAMP mice treated with castration and/or 5′‐Aza‐2′‐deoxycytidine (5Aza). RESULTS Immunohistochemical analysis revealed increased nuclear DNMT1 staining in localized PCa ( P  < 0.0001) and metastatic PCa ( P  < 0.0001) compared to normal tissue. Examination of specific diagnoses revealed that Gleason seven tumors exhibited greater nuclear DNMT1 staining than Gleason six tumors ( P  < 0.05) and that metastatic tissue exhibited greater levels of nuclear DNMT1 than Gleason seven tumors ( P  < 0.01). Evaluation of the murine tissue cores revealed that 8.2% and 8.1% of benign tissue cores stained positive for E2F1 and DNMT1 respectively, while 97.0% were AR positive. Conversely, 81% and 100% of tumors were positive for E2F1and DNMT1 respectively. This was in stark contrast to only 18% of tumors positive for AR. Treatment of mice with 5Aza reduced DNMT1 staining by 30%, while AR increased by 27%. CONCLUSIONS These findings demonstrate that the E2F1/DNMT1 inhibitory axis of AR transcription is activated during the emergence of CRPC. Prostate 73:1776–1785, 2013 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100341/1/pros22715.pd

Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

HISTONE DEACETYLASE 9 stimulates auxin-dependent thermomorphogenesis in Arabidopsis thaliana by mediating H2A.Z depletion

Many plant species respond to unfavorable high ambient temperatures by adjusting their vegetative body plan to facilitate cooling. This process is known as thermomorphogenesis and is induced by the phytohormone auxin. Here, we demonstrate that the chromatin-modifying enzyme HISTONE DEACETYLASE 9 (HDA9) mediates thermomorphogenesis but does not interfere with hypocotyl elongation during shade avoidance. HDA9 is stabilized in response to high temperature and mediates histone deacetylation at the YUCCA8 locus, a rate-limiting enzyme in auxin biosynthesis, at warm temperatures. We show that HDA9 permits net eviction of the H2A.Z histone variant from nucleosomes associated with YUCCA8, allowing binding and transcriptional activation by PHYTOCHROME INTERACTING FACTOR 4, followed by auxin accumulation and thermomorphogenesis

Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3

Context. Recently, the high-energy (HE, 0.1-100 GeV) $\gamma$-ray emission from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered to be modulated with a 10.3-day period, making it the first extra-galactic $\gamma$-ray binary. Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV) $\gamma$-ray emission and the search for modulation of the VHE signal with the orbital period of the binary system. Methods. LMC P3 has been observed with the High Energy Stereoscopic System (H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has been folded with the known orbital period of the system in order to test for variability of the emission. Energy spectra are obtained for the orbit-averaged data set, and for the orbital phase bin around the VHE maximum. Results. VHE $\gamma$-ray emission is detected with a statistical significance of 6.4 $\sigma$. The data clearly show variability which is phase-locked to the orbital period of the system. Periodicity cannot be deduced from the H.E.S.S. data set alone. The orbit-averaged luminosity in the $1-10$ TeV energy range is $(1.4 \pm 0.2) \times 10^{35}$ erg/s. A luminosity of $(5 \pm 1) \times 10^{35}$ erg/s is reached during 20% of the orbit. HE and VHE $\gamma$-ray emissions are anti-correlated. LMC P3 is the most luminous $\gamma$-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&

Is there an association between depressive and urinary symptoms during and after pregnancy?

Depressive symptoms and urinary symptoms are both highly prevalent in pregnancy. In the general population, an association is reported between urinary symptoms and depressive symptoms. The association of depressive and urinary symptoms has not yet been assessed in pregnancy. In this study, we assessed (1) the prevalence of depressive symptoms, over-active bladder (OAB) syndrome, urge urinary incontinence (UUI) and stress urinary incontinence (SUI) during and after pregnancy using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Urogenital Distress Inventory (UDI) and (2) the association of depressive symptoms with urinary incontinence and over-active bladder syndrome during and after pregnancy, controlling for confounding socioeconomic, psychosocial, behavioural and biomedical factors in a cohort of healthy nulliparous women. Our data show a significant increase in prevalence of depressive symptoms, UUI, SUI and OAB during pregnancy and a significant reduction in prevalence of depressive symptoms, SUI and OAB after childbirth. UUI prevalence did not significantly decrease after childbirth. In univariate analysis, urinary incontinence and the OAB syndrome were significantly associated with a CES-D score indicative of a possible clinical depression at 36 weeks gestation. However, after adjusting for possible confounding factors, only the OAB syndrome remained significantly associated (OR 4.4 [1.8–10.5]). No association was found between depressive and urinary symptoms at 1 year post-partum. Only OAB was independently associated with depressive symptoms during pregnancy. Possible explanations for this association are discussed

The pathophysiology of chronic graft-versus-host disease: the unveiling of an enigma

Chronic graft-versus-host disease (CGVHD) is one of the most significant complications of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT). CGVHD may have protean manifestations and can pose unique diagnostic and therapeutic challenges. New recommendations that emphasize the importance of qualitative differences, as opposed to time of onset after HSCT, are now being used to standardize the diagnosis and clinical assessment of CGVHD, but they require validation. During the past 3 decades, experimental studies and clinical observations have elucidated the mechanisms of acute GVHD, but its biology is much less well-understood. Experimental studies have generated at least 4 theories to explain the pathophysiology of CGVHD: (1) thymic damage and the defective negative selection of T cells, (2) regulatory T cell deficiencies, (3) auto-antibody production by aberrant B cells, and (4) the formation of profibrotic lesions. Mouse models have provided important insights into the pathophysiology of CGVHD, and these have helped improve clinical outcomes following allo-HSCT, but no animal model fully replicates all of the features of CGVHD in humans. In this article, recent clinical changes, the pathogenesis of CGHVD, the cellular and cytokine networks implicated in its pathogenesis, and the animal models used to devise strategies to prevent and treat CGVHD are reviewed

Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas.

BACKGROUND: Nonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas. METHODS: Quantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples. RESULTS: Increased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p < 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p < 0.05). CONCLUSIONS: Methylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations