When It Strikes, Are We Ready? Lessons Identified at the 7th Planetary Defense Conference in Preparing for a Near-Earth Object Impact Scenario

Abstract Near-Earth object (NEO) impact is one of the examples of high impact and low probability (HILP) event, same as the Covid-19 pandemic the world faces since the beginning of 2020. The 7th Planetary Defense Conference held by the International Academy of Astronautics (IAA) in April 2021 included an exercise on a hypothetical NEO impact event, allowing the planetary defense community to discuss potential responses. Over the span of the 4-day conference this exercise connected disaster response and management professionals to participate in a series of panels, providing feedback and perspective on the unfolding crisis scenario. The hypothetical but realistic asteroid threat scenario illustrated how such a short-warning threat might evolve. The scenario utilized during the conference indicates a need to prepare now for what might come in the future, because even with advance notice, preparation time might be minimal. This scenario chose Europe for the impact, which may likely cope with such a disaster, through the Union Civil Protection Mechanism (UCPM) and other solidarity and support mechanisms within the European Union (EU), as well as with potential support from international partners. This short article raises concern about other areas in the world on how they may access NEO impact information and cope with such disasters. It also provides an idea on vast scale of such disaster vis-à-vis the current capacity of response systems to cope with a larger event in Europe or elsewhere. This scenario showed that planetary defense is a global endeavor. Constant engagement of the planetary defense and disaster response communities is essential in order to keep the world safe from potential disasters caused by NEO impacts.</jats:p

Orthorexic tendencies are linked with difficulties with emotion identification and regulation.

Background: Orthorexia nervosa (ON) is characterised by an unhealthy obsession with healthy eating and while it is not recognised as an eating disorder (or any disorder), current research is exploring similarities and differences with such disorders. The literature has shown that individuals with eating disorders have difficulties identifying and describing emotions (known as alexithymia) as well as regulating them. However no research to date has looked at whether people with orthorexic tendencies also suffer from difficulties with emotions. In this paper, we refer to people with orthorexic tendencies but do not assume that their healthy eating is at a pathological level needing clinical attention. Methods: The current study examined this by asking 196 healthy adults with an interest in healthy eating to complete four questionnaires to measure ON (ORTO-15 - reduced to ORTO-7CS), eating psychopathology (EAT-26), alexithymia (TAS-20) and emotion dysregulation (DERS-16). Results: We found that difficulties identifying and regulating emotions was associated with symptoms of ON, similar to what is found in other eating disorders. We suggest that ON behaviours may be used as a coping strategy in order to feel in control in these participants who have poor emotion regulation abilities. Conclusions: Our results show that individuals with ON tendencies may share similar difficulties with emotions compared to other eating disorders. While important, our results are limited by the way we measured ON behaviours and we recommend that further research replicate our findings once a better and more specific tool is developed and validated to screen for ON characteristics more accurately

Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death

This work was supported by Agencia Aragonesa para la Investigación y Desarrollo (ARAID), Ministerio de Economía y Competitividad (CTQ2013-44367-C2-2-P to R.H.-G.) and Diputación General de Aragón (DGA; B89 to R.H.-G.) and the EU Seventh Framework Programme (2007–2013) under BioStruct-X (grant agreement 283570 and BIOSTRUCTX 5186, to R.H.-G.). T.K.S. was supported by the Wellcome Trust grant 093228 and European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED).Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite’s growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.Publisher PDFPeer reviewe

Involvement of the exomer complex in the polarized transport of Ena1 required for Saccharomyces cerevisiae survival against toxic cations

[EN] Exomer is an adaptor complex required for the direct transport of a selected number of cargoes from the trans-Golgi network (TGN) to the plasma membrane in Saccharomyces cerevisiae However, exomer mutants are highly sensitive to increased concentrations of alkali metal cations, a situation that remains unexplained by the lack of transport of any known cargoes. Here we identify several HAL genes that act as multicopy suppressors of this sensitivity and are connected to the reduced function of the sodium ATPase Ena1. Furthermore, we find that Ena1 is dependent on exomer function. Even though Ena1 can reach the plasma membrane independently of exomer, polarized delivery of Ena1 to the bud requires functional exomer. Moreover, exomer is required for full induction of Ena1 expression after cationic stress by facilitating the plasma membrane recruitment of the molecular machinery involved in Rim101 processing and activation of the RIM101 pathway in response to stress. Both the defective localization and the reduced levels of Ena1 contribute to the sensitivity of exomer mutants to alkali metal cations. Our work thus expands the spectrum of exomer-dependent proteins and provides a link to a more general role of exomer in TGN organization.We acknowledge Emma Keck for English language revision. We also thank members of the Translucent group, J. Arino, J. Ramos, and L. Yenush, for many useful discussions throughout this work and especially L. Yenush for her generous gift of strains and reagents. The help of O. Vincent was essential for developing the work involving RIM101. We also thank R. Valle for her technical assistance at the CR Laboratory. M. Trautwein is acknowledged for data acquisition and discussions during the early stages of the project. C.A. is supported by a USAL predoctoral fellowship. Work at the Spang laboratory was supported by the University of Basel and the Swiss National Science Foundation (31003A-141207 and 310030B-163480). C.R. was supported by grant SA073U14 from the Regional Government of Castilla y Leon and by grant BFU2013-48582-C2-1-P from the CICYT/FEDER Spanish program. J.M.M. acknowledges the financial support from Universitat Politecnica de Valencia project PAID-06-10-1496.Anton, C.; Zanolari, B.; Arcones, I.; Wang, C.; Mulet, JM.; Spang, A.; Roncero, C. (2017). Involvement of the exomer complex in the polarized transport of Ena1 required for Saccharomyces cerevisiae survival against toxic cations. Molecular Biology of the Cell. 28(25):3672-3685. https://doi.org/10.1091/mbc.E17-09-0549S367236852825Ariño, J., Ramos, J., & Sychrová, H. (2010). Alkali Metal Cation Transport and Homeostasis in Yeasts. Microbiology and Molecular Biology Reviews, 74(1), 95-120. doi:10.1128/mmbr.00042-09Bard, F., & Malhotra, V. (2006). The Formation of TGN-to-Plasma-Membrane Transport Carriers. Annual Review of Cell and Developmental Biology, 22(1), 439-455. doi:10.1146/annurev.cellbio.21.012704.133126Barfield, R. M., Fromme, J. C., & Schekman, R. (2009). The Exomer Coat Complex Transports Fus1p to the Plasma Membrane via a Novel Plasma Membrane Sorting Signal in Yeast. Molecular Biology of the Cell, 20(23), 4985-4996. doi:10.1091/mbc.e09-04-0324Bonifacino, J. S. (2014). Adaptor proteins involved in polarized sorting. Journal of Cell Biology, 204(1), 7-17. doi:10.1083/jcb.201310021Bonifacino, J. S., & Glick, B. S. (2004). The Mechanisms of Vesicle Budding and Fusion. Cell, 116(2), 153-166. doi:10.1016/s0092-8674(03)01079-1Bonifacino, J. S., & Lippincott-Schwartz, J. (2003). Coat proteins: shaping membrane transport. Nature Reviews Molecular Cell Biology, 4(5), 409-414. doi:10.1038/nrm1099Carlson, M., & Botstein, D. (1982). Two differentially regulated mRNAs with different 5′ ends encode secreted and intracellular forms of yeast invertase. Cell, 28(1), 145-154. doi:10.1016/0092-8674(82)90384-1Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E. D., Sevier, C. S., … Mostafavi, S. (2010). The Genetic Landscape of a Cell. Science, 327(5964), 425-431. doi:10.1126/science.1180823De Matteis, M. A., & Luini, A. (2008). Exiting the Golgi complex. Nature Reviews Molecular Cell Biology, 9(4), 273-284. doi:10.1038/nrm2378De Nadal, E., Clotet, J., Posas, F., Serrano, R., Gomez, N., & Arino, J. (1998). The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase. Proceedings of the National Academy of Sciences, 95(13), 7357-7362. doi:10.1073/pnas.95.13.7357Drubin, D. G., & Nelson, W. J. (1996). Origins of Cell Polarity. Cell, 84(3), 335-344. doi:10.1016/s0092-8674(00)81278-7Fell, G. L., Munson, A. M., Croston, M. A., & Rosenwald, A. G. (2011). Identification of Yeast Genes Involved in K+Homeostasis: Loss of Membrane Traffic Genes Affects K+Uptake. G3&amp;#58; Genes|Genomes|Genetics, 1(1), 43-56. doi:10.1534/g3.111.000166Ferrando, A., Kron, S. J., Rios, G., Fink, G. R., & Serrano, R. (1995). Regulation of cation transport in Saccharomyces cerevisiae by the salt tolerance gene HAL3. Molecular and Cellular Biology, 15(10), 5470-5481. doi:10.1128/mcb.15.10.5470Forsmark, A., Rossi, G., Wadskog, I., Brennwald, P., Warringer, J., & Adler, L. (2011). Quantitative Proteomics of Yeast Post-Golgi Vesicles Reveals a Discriminating Role for Sro7p in Protein Secretion. Traffic, 12(6), 740-753. doi:10.1111/j.1600-0854.2011.01186.xGaber, R. F., Styles, C. A., & Fink, G. R. (1988). TRK1 encodes a plasma membrane protein required for high-affinity potassium transport in Saccharomyces cerevisiae. Molecular and Cellular Biology, 8(7), 2848-2859. doi:10.1128/mcb.8.7.2848Galindo, A., Calcagno-Pizarelli, A. M., Arst, H. N., & Penalva, M. A. (2012). An ordered pathway for the assembly of fungal ESCRT-containing ambient pH signalling complexes at the plasma membrane. Journal of Cell Science, 125(7), 1784-1795. doi:10.1242/jcs.098897Goldstein, A. L., & McCusker, J. H. (1999). Three new dominant drug resistance cassettes for gene disruption inSaccharomyces cerevisiae. Yeast, 15(14), 1541-1553. doi:10.1002/(sici)1097-0061(199910)15:143.0.co;2-kHayashi, M., Fukuzawa, T., Sorimachi, H., & Maeda, T. (2005). Constitutive Activation of the pH-Responsive Rim101 Pathway in Yeast Mutants Defective in Late Steps of the MVB/ESCRT Pathway. Molecular and Cellular Biology, 25(21), 9478-9490. doi:10.1128/mcb.25.21.9478-9490.2005Herrador, A., Herranz, S., Lara, D., & Vincent, O. (2009). Recruitment of the ESCRT Machinery to a Putative Seven-Transmembrane-Domain Receptor Is Mediated by an Arrestin-Related Protein. Molecular and Cellular Biology, 30(4), 897-907. doi:10.1128/mcb.00132-09Herrador, A., Livas, D., Soletto, L., Becuwe, M., Léon, S., & Vincent, O. (2015). Casein kinase 1 controls the activation threshold of an α-arrestin by multisite phosphorylation of the interdomain hinge. Molecular Biology of the Cell, 26(11), 2128-2138. doi:10.1091/mbc.e14-11-1552Herranz, S., Rodriguez, J. M., Bussink, H.-J., Sanchez-Ferrero, J. C., Arst, H. N., Penalva, M. A., & Vincent, O. (2005). Arrestin-related proteins mediate pH signaling in fungi. Proceedings of the National Academy of Sciences, 102(34), 12141-12146. doi:10.1073/pnas.0504776102Hoya, M., Yanguas, F., Moro, S., Prescianotto-Baschong, C., Doncel, C., de León, N., … Valdivieso, M.-H. (2016). Traffic Through theTrans-Golgi Network and the Endosomal System Requires Collaboration Between Exomer and Clathrin Adaptors in Fission Yeast. Genetics, 205(2), 673-690. doi:10.1534/genetics.116.193458Huranova, M., Muruganandam, G., Weiss, M., & Spang, A. (2016). Dynamic assembly of the exomer secretory vesicle cargo adaptor subunits. EMBO reports, 17(2), 202-219. doi:10.15252/embr.201540795Kung, L. F., Pagant, S., Futai, E., D’Arcangelo, J. G., Buchanan, R., Dittmar, J. C., … Miller, E. A. (2011). Sec24p and Sec16p cooperate to regulate the GTP cycle of the COPII coat. The EMBO Journal, 31(4), 1014-1027. doi:10.1038/emboj.2011.444Lamb, T. M., & Mitchell, A. P. (2003). The Transcription Factor Rim101p Governs Ion Tolerance and Cell Differentiation by Direct Repression of the Regulatory Genes NRG1 and SMP1 in Saccharomyces cerevisiae. Molecular and Cellular Biology, 23(2), 677-686. doi:10.1128/mcb.23.2.677-686.2003Lamb, T. M., Xu, W., Diamond, A., & Mitchell, A. P. (2000). Alkaline Response Genes ofSaccharomyces cerevisiaeand Their Relationship to theRIM101Pathway. Journal of Biological Chemistry, 276(3), 1850-1856. doi:10.1074/jbc.m008381200Madrid, R., Gómez, M. J., Ramos, J., & Rodrı́guez-Navarro, A. (1998). Ectopic Potassium Uptake intrk1 trk2Mutants ofSaccharomyces cerevisiaeCorrelates with a Highly Hyperpolarized Membrane Potential. Journal of Biological Chemistry, 273(24), 14838-14844. doi:10.1074/jbc.273.24.14838Maresova, L., & Sychrova, H. (2004). Physiological characterization of Saccharomyces cerevisiae kha1 deletion mutants. Molecular Microbiology, 55(2), 588-600. doi:10.1111/j.1365-2958.2004.04410.xMarqués, M. C., Zamarbide-Forés, S., Pedelini, L., Llopis-Torregrosa, V., & Yenush, L. (2015). A functional Rim101 complex is required for proper accumulation of the Ena1 Na+-ATPase protein in response to salt stress in Saccharomyces cerevisiae. FEMS Yeast Research, 15(4). doi:10.1093/femsyr/fov017Mulet, J. M., Leube, M. P., Kron, S. J., Rios, G., Fink, G. R., & Serrano, R. (1999). A Novel Mechanism of Ion Homeostasis and Salt Tolerance in Yeast: the Hal4 and Hal5 Protein Kinases Modulate the Trk1-Trk2 Potassium Transporter. Molecular and Cellular Biology, 19(5), 3328-3337. doi:10.1128/mcb.19.5.3328Mulet, J. M., & Serrano, R. (2002). Simultaneous determination of potassium and rubidium content in yeast. Yeast, 19(15), 1295-1298. doi:10.1002/yea.909Murguía, J. R., Bellés, J. M., & Serrano, R. (1996). The YeastHAL2Nucleotidase Is anin VivoTarget of Salt Toxicity. Journal of Biological Chemistry, 271(46), 29029-29033. doi:10.1074/jbc.271.46.29029Obara, K., & Kihara, A. (2014). Signaling Events of the Rim101 Pathway Occur at the Plasma Membrane in a Ubiquitination-Dependent Manner. Molecular and Cellular Biology, 34(18), 3525-3534. doi:10.1128/mcb.00408-14Paczkowski, J. E., & Fromme, J. C. (2014). Structural Basis for Membrane Binding and Remodeling by the Exomer Secretory Vesicle Cargo Adaptor. Developmental Cell, 30(5), 610-624. doi:10.1016/j.devcel.2014.07.014Paczkowski, J. E., Richardson, B. C., & Fromme, J. C. (2015). Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis. Trends in Cell Biology, 25(7), 408-416. doi:10.1016/j.tcb.2015.02.005Paczkowski, J. E., Richardson, B. C., Strassner, A. M., & Fromme, J. C. (2012). The exomer cargo adaptor structure reveals a novel GTPase-binding domain. The EMBO Journal, 31(21), 4191-4203. doi:10.1038/emboj.2012.268Parsons, A. B., Brost, R. L., Ding, H., Li, Z., Zhang, C., Sheikh, B., … Boone, C. (2003). Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nature Biotechnology, 22(1), 62-69. doi:10.1038/nbt919Peñalva, M. A., Lucena-Agell, D., & Arst, H. N. (2014). Liaison alcaline: Pals entice non-endosomal ESCRTs to the plasma membrane for pH signaling. Current Opinion in Microbiology, 22, 49-59. doi:10.1016/j.mib.2014.09.005Ríos, G., Cabedo, M., Rull, B., Yenush, L., Serrano, R., & Mulet, J. M. (2013). Role of the yeast multidrug transporter Qdr2 in cation homeostasis and the oxidative stress response. FEMS Yeast Research, 13(1), 97-106. doi:10.1111/1567-1364.12013RIOS, G., FERRANDO, A., & SERRANO, R. (1997). Mechanisms of Salt Tolerance Conferred by Overexpression of theHAL1 Gene inSaccharomyces cerevisiae. Yeast, 13(6), 515-528. doi:10.1002/(sici)1097-0061(199705)13:63.0.co;2-xRitz, A. M., Trautwein, M., Grassinger, F., & Spang, A. (2014). The Prion-like Domain in the Exomer-Dependent Cargo Pin2 Serves as a trans-Golgi Retention Motif. Cell Reports, 7(1), 249-260. doi:10.1016/j.celrep.2014.02.026Rockenbauch, U., Ritz, A. M., Sacristan, C., Roncero, C., & Spang, A. (2012). The complex interactions of Chs5p, the ChAPs, and the cargo Chs3p. Molecular Biology of the Cell, 23(22), 4402-4415. doi:10.1091/mbc.e11-12-1015Roncero, C. (2002). The genetic complexity of chitin synthesis in fungi. Current Genetics, 41(6), 367-378. doi:10.1007/s00294-002-0318-7Rothfels, K., Tanny, J. C., Molnar, E., Friesen, H., Commisso, C., & Segall, J. (2005). Components of the ESCRT Pathway, DFG16, and YGR122w Are Required for Rim101 To Act as a Corepressor with Nrg1 at the Negative Regulatory Element of the DIT1 Gene of Saccharomyces cerevisiae. Molecular and Cellular Biology, 25(15), 6772-6788. doi:10.1128/mcb.25.15.6772-6788.2005Santos, B., & Snyder, M. (1997). Targeting of Chitin Synthase 3 to Polarized Growth Sites in Yeast Requires Chs5p and Myo2p. Journal of Cell Biology, 136(1), 95-110. doi:10.1083/jcb.136.1.95Sato, M., Dhut, S., & Toda, T. (2005). New drug-resistant cassettes for gene disruption and epitope tagging inSchizosaccharomyces pombe. Yeast, 22(7), 583-591. doi:10.1002/yea.1233Schekman, R., & Orci, L. (1996). Coat Proteins and Vesicle Budding. Science, 271(5255), 1526-1533. doi:10.1126/science.271.5255.1526Sopko, R., Huang, D., Preston, N., Chua, G., Papp, B., Kafadar, K., … Andrews, B. (2006). Mapping Pathways and Phenotypes by Systematic Gene Overexpression. Molecular Cell, 21(3), 319-330. doi:10.1016/j.molcel.2005.12.011Spang, A. (2008). Membrane traffic in the secretory pathway. Cellular and Molecular Life Sciences, 65(18), 2781-2789. doi:10.1007/s00018-008-8349-yStarr, T. L., Pagant, S., Wang, C.-W., & Schekman, R. (2012). Sorting Signals That Mediate Traffic of Chitin Synthase III between the TGN/Endosomes and to the Plasma Membrane in Yeast. PLoS ONE, 7(10), e46386. doi:10.1371/journal.pone.0046386Trautwein, M., Schindler, C., Gauss, R., Dengjel, J., Hartmann, E., & Spang, A. (2006). Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi. The EMBO Journal, 25(5), 943-954. doi:10.1038/sj.emboj.7601007Trilla, J. A., Durán, A., & Roncero, C. (1999). Chs7p, a New Protein Involved in the Control of Protein Export from the Endoplasmic Reticulum that Is Specifically Engaged in the Regulation of Chitin Synthesis in Saccharomyces cerevisiae. Journal of Cell Biology, 145(6), 1153-1163. doi:10.1083/jcb.145.6.1153Valdivia, R. H., Baggott, D., Chuang, J. S., & Schekman, R. W. (2002). The Yeast Clathrin Adaptor Protein Complex 1 Is Required for the Efficient Retention of a Subset of Late Golgi Membrane Proteins. Developmental Cell, 2(3), 283-294. doi:10.1016/s1534-5807(02)00127-2Wadskog, I., Forsmark, A., Rossi, G., Konopka, C., Öyen, M., Goksör, M., … Adler, L. (2006). The Yeast Tumor Suppressor Homologue Sro7p Is Required for Targeting of the Sodium Pumping ATPase to the Cell Surface. Molecular Biology of the Cell, 17(12), 4988-5003. doi:10.1091/mbc.e05-08-0798Wang, C.-W., Hamamoto, S., Orci, L., & Schekman, R. (2006). Exomer: a coat complex for transport of select membrane proteins from the trans-Golgi network to the plasma membrane in yeast. Journal of Cell Biology, 174(7), 973-983. doi:10.1083/jcb.200605106Weiskoff, A. M., & Fromme, J. C. (2014). Distinct N-terminal regions of the exomer secretory vesicle cargo Chs3 regulate its trafficking itinerary. Frontiers in Cell and Developmental Biology, 2. doi:10.3389/fcell.2014.00047Yahara, N., Ueda, T., Sato, K., & Nakano, A. (2001). Multiple Roles of Arf1 GTPase in the Yeast Exocytic and Endocytic Pathways. Molecular Biology of the Cell, 12(1), 221-238. doi:10.1091/mbc.12.1.221Yenush, L., Merchan, S., Holmes, J., & Serrano, R. (2005). pH-Responsive, Posttranslational Regulation of the Trk1 Potassium Transporter by the Type 1-Related Ppz1 Phosphatase. Molecular and Cellular Biology, 25(19), 8683-8692. doi:10.1128/mcb.25.19.8683-8692.2005Yenush, L. (2002). The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression. The EMBO Journal, 21(5), 920-929. doi:10.1093/emboj/21.5.920Zanolari, B., Rockenbauch, U., Trautwein, M., Clay, L., Barral, Y., & Spang, A. (2011). Transport to the plasma membrane is regulated differently early and late in the cell cycle in Saccharomyces cerevisiae. Journal of Cell Science, 124(7), 1055-1066. doi:10.1242/jcs.07237

Histopathological alterations in Senegal sole, Solea Senegalensis, from a polluted Huelva estuary (SW, Spain)

As a component of a large research project to evaluate the effects of contaminants on fish health in the field, histopathological studies have been conducted to help establish causal relationship between pollutants (heavy metals and aromatic polycyclic hydrocarbons—PAHs) and histopathological responses in Senegal sole, Solea senegalensis, from an estuary of SW Spain. Heavy metals (As, Zn, Cd, Pb, Cu and Fe) and 16 PAHs (proprietary USEPA) concentrations in water, sediment and tissues (liver and gills) and histopathological alterations in S. senegalensis from three sampling sites of Ria de Huelva estuary during 2004–2006 years have been analysed. The histopathological studies revealed seasonal and spatial differences in the lesion grade of alterations observing the highest lesion grades in fish from Odiel River and autumn season. No significant differences were observed in the alterations prevalence between sampling sites, but significant differences were observed between seasons observing the highest prevalence in autumn season. However, calculated IPAT demonstrated a low–moderate impact of pollutants on health fish. Correlations between histopathological alterations and pollutants analysed were observed being heavy metals the group that presented a major number of correlations with alterations in several organs of S. senegalensis. In evaluating the general health of fish, the use of histopathological studies in recommended for making more reliable assessment of biochemical responses in fish exposed to a variety of environmental stressors. Statistical analysis using semiquantitative data on pathological lesions can help to establish correlation between cause (stressor) and effect (biomarker)

Two Origins for the Gene Encoding α-Isopropylmalate Synthase in Fungi

BACKGROUND: The biosynthesis of leucine is a biochemical pathway common to prokaryotes, plants and fungi, but absent from humans and animals. The pathway is a proposed target for antimicrobial therapy. METHODOLOGY/PRINCIPAL FINDINGS: Here we identified the leuA gene encoding alpha-isopropylmalate synthase in the zygomycete fungus Phycomyces blakesleeanus using a genetic mapping approach with crosses between wild type and leucine auxotrophic strains. To confirm the function of the gene, Phycomyces leuA was used to complement the auxotrophic phenotype exhibited by mutation of the leu3+ gene of the ascomycete fungus Schizosaccharomyces pombe. Phylogenetic analysis revealed that the leuA gene in Phycomyces, other zygomycetes, and the chytrids is more closely related to homologs in plants and photosynthetic bacteria than ascomycetes or basidiomycetes, and suggests that the Dikarya have acquired the gene more recently. CONCLUSIONS/SIGNIFICANCE: The identification of leuA in Phycomyces adds to the growing body of evidence that some primary metabolic pathways or parts of them have arisen multiple times during the evolution of fungi, probably through horizontal gene transfer events

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Professionals&rsquo; perception on the management of patients with dual disorders

Carlos Roncero,1,2 N&eacute;stor Szerman,3 Antonio Ter&aacute;n,4 Carlos Pino,5 Jos&eacute; Mar&iacute;a V&aacute;zquez,6 Elena Velasco,7 Marta Garc&iacute;a-Dorado,7 Miguel Casas1,2 1Addiction and Dual Diagnosis Unit, CIBERSAM, Hospital Vall Hebron, Barcelona Public Health Agency (ASPB), Barcelona, Spain; 2Department of Psychiatry, Autonomous University of Barcelona, Barcelona, Spain; 3Outpatient Mental Health Clinic El Retiro, Gregorio Mara&ntilde;&oacute;n University Hospital, Madrid, Spain; 4Outpatient Drug Clinic, Hospital San Juan de Dios, Palencia, Spain; 5Pontevedra City Council Drug Dependence Service, Galician Health Service (Xunta de Galicia), Pontevedra, Spain; 6Outpatient Drug Clinic Sants, Barcelona Public Health Agency (ASPB), Barcelona, Spain; 7Medical Affairs Department, Janssen-Cilag S.A., Madrid, Spain Background: There is a need to evaluate the professionals&rsquo; perception about the consequences of the lack of therapeutic adherence in the evolution of patients with co-occurring disorders.Methods: An online survey, released on the Socidrogalcohol [Spanish Scientific Society for Research on Alcohol, Alcoholism and other Drug Addic&shy;tions] and Sociedad Espa&ntilde;ola de Patolog&iacute;a Dual [the Spanish Society of Dual Pathology] web pages, was answered by 250 professionals who work in different types of Spanish health centers where dual diagnosis patients are assisted.Results: Most professionals perceived the existence of noncompliance among dual diagnosis patients. Almost all of these professionals (99%) perceived that noncompliance leads to a worsening of the progression of the patient&rsquo;s disorder, in both the exacerbation of mental disorders and the consumption of addictive substances. Most of the professionals (69.2%) considered therapeutic alliance as the main aspect to take into account to improve the prognosis in this population. The primary purpose of treatment must be the improvement of psychotic-phase positive symptoms, followed by the control of behavior disorders, reduction of craving, improvement of social and personal performances, and reduction of psychotic-phase negative symptoms.Conclusion: Most professionals perceived low adherence among dual diagnosis patients. This lack of adherence is associated with a worsening of their disease evolution, which is reflected in exacerbations of the psychopathology and relapse in substance use. Therefore, we propose to identify strategies to improve adherence. Keywords: dual diagnosis, professionals&rsquo; perception, noncompliance, decompensation, relaps