Air pollution during the 2003 European heat wave as seen by MOZAIC airliners

This study presents an analysis of both MOZAIC profiles above Frankfurt and Lagrangian dispersion model simulations for the 2003 European heat wave. The comparison of MOZAIC measurements in summer 2003 with the 11-year MOZAIC climatology reflects strong temperature anomalies (exceeding 4°C) throughout the lower troposphere. Higher positive anomalies of temperature and negative anomalies of both wind speed and relative humidity are found for the period defined here as the heat wave (2–14 August 2003), compared to the periods before (16–31 July 2003) and after (16–31 August 2003) the heat wave. In addition, Lagrangian model simulations in backward mode indicate the suppressed long-range transport in the mid- to lower troposphere and the enhanced southern origin of air masses for all tropospheric levels during the heat wave. Ozone and carbon monoxide also present strong anomalies (both ~+40 ppbv) during the heat wave, with a maximum vertical extension reaching 6 km altitude around 11 August 2003. Pollution in the planetary boundary layer (PBL) is enhanced during the day, with ozone mixing ratios two times higher than climatological values. This is due to a combination of factors, such as high temperature and radiation, stagnation of air masses and weak dry deposition, which favour the accumulation of ozone precursors and the build-up of ozone. A negligible role of a stratospheric-origin ozone tracer has been found for the lower troposphere in this study. From 29 July to 15 August 2003 forest fires burnt around 0.3×10<sup>6</sup> ha in Portugal and added to atmospheric pollution in Europe. Layers with enhanced CO and NO<sub>y</sub> mixing ratios, advected from Portugal, were crossed by the MOZAIC aircraft in the free troposphere over Frankfurt. A series of forward and backward Lagrangian model simulations have been performed to investigate the origin of anomalies during the whole heat wave. European anthropogenic emissions present the strongest contribution to the measured CO levels in the lower troposphere (near 30%). This source is followed by Portuguese forest fires which affect the lower troposphere after 6 August 2003 and even the PBL around 10 August 2003. The averaged biomass burning contribution reaches 35% during the affected period. Anthropogenic CO of North American origin only marginally influences CO levels over Europe during that period

The use of 3D-printed models in patient communication: a scoping review

3D models have been used as an asset in many clinical applications and a variety of disciplines, and yet the available literature studying the use of 3D models in communication is limited. This scoping review has been conducted to draw conclusions on the current evidence and learn from previous studies, using this knowledge to inform future work. Our search strategy revealed 269 papers, 19 of which were selected for final inclusion and analysis. When assessing the use of 3D models in doctor-patient communication, there is a need for larger studies and studies including a long-term follow up. Furthermore, there are forms of communication that are yet to be researched and provide a niche that may be beneficial to explore

Modeling interactions between transposable elements and the plant epigenetic response: a surprising reliance on element retention

Transposable elements (TEs) compose the majority of angiosperm DNA. Plants counteract TE activity by silencing them epigenetically. One form of epigenetic silencing requires 21-22 nt small interfering RNAs that act to degrade TE mRNA and may also trigger DNA methylation. DNA methylation is reinforced by a second mechanism, the RNA-dependent DNA methylation (RdDM) pathway. RdDM relies on 24 nt small interfering RNAs and ultimately establishes TEs in a quiescent state. These host factors interact at a systems level, but there have been no system level analyses of their interactions. Here, we define a deterministic model that represents the propagation of active TEs, aspects of the host response and the accumulation of silenced TEs. We describe general properties of the model and also fit it to biological data in order to explore two questions. The first is why two overlapping pathways are maintained, given that both are likely energetically expensive. Under our model, RdDM silenced TEs effectively even when the initiation of silencing was weak. This relationship implies that only a small amount of RNAi is needed to initiate TE silencing, but reinforcement by RdDM is necessary to efficiently counter TE propagation. Second, we investigated the reliance of the host response on rates of TE deletion. The model predicted that low levels of deletion lead to few active TEs, suggesting that silencing is most efficient when methylated TEs are retained in the genome, thereby providing one explanation for the large size of plant genomes

Mechanistic and evolutionary questions about epigenetic conflicts between transposable elements and their plant hosts

Transposable elements (TEs) constitute the majority of plant genomes, but most are epigenetically inactivated by their host. Research over the last decade has elucidated many of the molecular components that are required for TE silencing. In contrast, the evolutionary dynamics between TEs and silencing pathways are less clear. Here, we discuss current information about these dynamics from both mechanistic and evolutionary perspectives. We highlight new evidence that palindromic sequences within TEs may act as signals for host recognition and that cis-regulatory regions of TEs may be sites of ongoing arms races with host defenses. We also discuss patterns of TE aging after they are silenced; while there is not yet a consensus, it appears that TEs are removed more rapidly near genes, such that older TE insertions tend to be farther from genes. We conclude by discussing the energetic costs for maintaining silencing pathways, which appear to be substantive. The maintenance of silencing pathways across many species suggests that epigenetic emergencies are frequent

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Kicking against the PRCs - a domesticated transposase antagonises silencing mediated by polycomb group proteins and is an accessory component of polycomb repressive complex 2

The Polycomb group (PcG) and trithorax group (trxG) genes play crucial roles in development by regulating expression of homeotic and other genes controlling cell fate. Both groups catalyse modifications of chromatin, particularly histone methylation, leading to epigenetic changes that affect gene activity. The trxG antagonizes the function of PcG genes by activating PcG target genes, and consequently trxG mutants suppress PcG mutant phenotypes. We previously identified the ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN1 (ALP1) gene as a genetic suppressor of mutants in the Arabidopsis PcG gene LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Here, we show that ALP1 interacts genetically with several other PcG and trxG components and that it antagonizes PcG silencing. Transcriptional profiling reveals that when PcG activity is compromised numerous target genes are hyper-activated in seedlings and that in most cases this requires ALP1. Furthermore, when PcG activity is present ALP1 is needed for full activation of several floral homeotic genes that are repressed by the PcG. Strikingly, ALP1 does not encode a known chromatin protein but rather a protein related to PIF/Harbinger class transposases. Phylogenetic analysis indicates that ALP1 is broadly conserved in land plants and likely lost transposase activity and acquired a novel function during angiosperm evolution. Consistent with this, immunoprecipitation and mass spectrometry (IP-MS) show that ALP1 associates, in vivo, with core components of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a widely conserved PcG protein complex which functions as a H3K27me3 histone methyltransferase. Furthermore, in reciprocal pulldowns using the histone methyltransferase CURLY LEAF (CLF), we identify not only ALP1 and the core PRC2 components but also plant-specific accessory components including EMBRYONIC FLOWER 1 (EMF1), a transcriptional repressor previously associated with PRC1-like complexes. Taken together our data suggest that ALP1 inhibits PcG silencing by blocking the interaction of the core PRC2 with accessory components that promote its HMTase activity or its role in inhibiting transcription. ALP1 is the first example of a domesticated transposase acquiring a novel function as a PcG component. The antagonistic interaction of a modified transposase with the PcG machinery is novel and may have arisen as a means for the cognate transposon to evade host surveillance or for the host to exploit features of the transposition machinery beneficial for epigenetic regulation of gene activity.Fil: Liang, Shih Chieh. University of Edinburgh; Reino UnidoFil: Hartwig, Ben. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Perera, Pumi. University of Edinburgh; Reino UnidoFil: Mora Garcia, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: de Leau, Erica. University of Edinburgh; Reino UnidoFil: Thornton, Harry. University of Edinburgh; Reino UnidoFil: Lima de Alves, Flavia. University of Edinburgh; Reino UnidoFil: Rapsilber, Juri. University of Edinburgh; Reino UnidoFil: Yang, Suxin. University of Edinburgh; Reino UnidoFil: James, Geo Velikkakam. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Schneeberger, Korbinian. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Finnegan, E. Jean. University of Edinburgh; Reino UnidoFil: Turck, Franziska. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Goodrich, Justin. Mc Gill University; Canad

SERBP1 is a component of the Liver Receptor Homolog-1 transcriptional complex

<p>Liver receptor homolog-1 (NR5A2) is an orphan nuclear receptor whose expression is essential for normal liver, intestine, and pancreas function. Nuclear receptors are ligand regulated transcription factors and NR5A2 has been shown to play a role in the transcriptional regulation of pathways involved in cancer. Elucidating the components of the NR5A2 transcriptional complex to better understand endogenous regulation of the receptor as well as its role in cancer remains a high priority. A sub-cellular enrichment strategy coupled with proteomic approaches was employed to identify putative NR5A2 coregulators. Nuclear fractionation protocol was essential for detection of NR5A2 peptides by MS, with most peptides being observed in the insoluble fraction (receptor bound to DNA). Duplicate data-dependent MS/MS runs using an inclusion/exclusion list improved the number of NR5A2 peptide identifications, including isoform-specific and fusion-specific peptides. Moreover, increased NR5A2 sequence coverage and a greater number of protein hits were observed with on-bead trypsin digestion of affinity captured protein. SERBP1 and ILF3 were identified as NR5A2 interacting partners. Both western blot and MS/MS analysis of endogenous receptor confirmed these binding partners are present in the NR5A2 transcriptional complex in established cell lines. Receptor knockdown by siRNA showed an increased in SERBP1 expression while ILF3 expression was unchanged. In contrast, receptor overexpression decreased only SERBP1 mRNA levels. Consistent with these data, in a promoter:reporter assay, binding of NR5A2 to the promoter region of SERBP1 resulted in a decrease in the expression level of the reporter gene, and subsequently, inhibiting transcription. In conclusion, using a sub-cellular enrichment strategy coupled with proteomic approaches, functionally relevant NR5A2 coregulators were identified. Given the receptor’s role in cancer progression, the study here elucidates additional transcriptional machinery involved in NR5A2 signaling and potentially provides new targets for therapeutics development.</p