A Bacterial Shortcut to Amyloidosis

21 p.-10 fig.The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible amyloid proteinopathy in Escherichia coli that inhibits growth and eventually kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through model lipid membranes, suggesting a possible mechanism for bacterial cell death. By comparing acutely (A31V) and mildly (ΔN37) cytotoxic mutant variants of the protein, we report here that RepA-WH1(A31V) expression decreases the intracellular osmotic pressure and compromise bacterial viability under either aerobic or anaerobic conditions. Both are effects expected from threatening membrane integrity and are in agreement with findings on the impairment by RepA-WH1(A31V) of the proton motive force (PMF)-dependent transport of ions (Fe3+) and ATP1 synthesis. Systems approaches reveal that, in aerobiosis, the PMF-independent respiratory dehydrogenase NdhII is induced in response to the reduction in intracellular levels of iron. While NdhII is known to generate H2O2 as a by-product of the autoxidation of its FAD cofactor, key proteins in the defense against oxidative stress (OxyR, KatE), together with other stress-resistance factors, are sequestered by co-aggregation with the RepA-WH1(A31V) amyloid. Our findings suggest a route for RepA-WH1 toxicity in bacteria: a primary hit of damage to the membrane, compromising bionergetics, triggers a stroke of oxidative stress, which is exacerbated due to the aggregation-dependent inactivation of enzymes and transcription factors that enable the cellular response to such injury. The proteinopathy caused by the prion-like protein RepA-WH1 in bacteria recapitulates some of the core hallmarks of human amyloid diseases.This work has been supported by grants from Spanish AEI / EU-FEDER (BIO2012-30852, BIO2015- 68730-R and CSD2009-00088) and CSIC (i-LINK0889) to R.G. We acknowledge support of the publication fee by the CSIC Open Access Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Are the health messages in schoolbooks based on scientific evidence? A descriptive study

<p>Abstract</p> <p>Background</p> <p>Most textbooks contains messages relating to health. This profuse information requires analysis with regards to the quality of such information. The objective was to identify the scientific evidence on which the health messages in textbooks are based.</p> <p>Methods</p> <p>The degree of evidence on which such messages are based was identified and the messages were subsequently classified into three categories: Messages with high, medium or low levels of evidence; Messages with an unknown level of evidence; and Messages with no known evidence.</p> <p>Results</p> <p>844 messages were studied. Of this total, 61% were classified as messages with an unknown level of evidence. Less than 15% fell into the category where the level of evidence was known and less than 6% were classified as possessing high levels of evidence. More than 70% of the messages relating to "Balanced Diets and Malnutrition", "Food Hygiene", "Tobacco", "Sexual behaviour and AIDS" and "Rest and ergonomics" are based on an unknown level of evidence. "Oral health" registered the highest percentage of messages based on a high level of evidence (37.5%), followed by "Pregnancy and newly born infants" (35%). Of the total, 24.6% are not based on any known evidence. Two of the messages appeared to contravene known evidence.</p> <p>Conclusion</p> <p>Many of the messages included in school textbooks are not based on scientific evidence. Standards must be established to facilitate the production of texts that include messages that are based on the best available evidence and which can improve children's health more effectively.</p

Human occupations of Northern Morocco, Middle and Upper Palaeolithic. New data on the basis of archaeological research projects from 2005 to 2020

Nous présentons dans ce travail, un panorama synthétique des occupations humaines du Nord du Maroc, en mettant l’accent sur l’association des données anthropologiques et des données culturelles, ceci dans un cadre chronologique compris entre le Paléolithique Moyen (MSA) et le Paléolithique Supérieur. Nous présentons aussi les projets développés, durant ces 15 dernières années, et les résultats les plus intéressants que nous avons obtenus. Pour conclure, nous proposons quelques réflexions sur l’évaluation culturelle et historique des enregistrements archéologiques de la région de Tétouan dans les périodes du Paléolithique Moyen et Supérieur.In this work, we present a synthetic panorama of the human occupations of northern Morocco, with an emphasis on the association of anthropological with cultural records, within the framework of the Middle Palaeolithic (MSA) and the Upper Palaeolithic. We also present the projects developed over the past 15 years and the most interesting results we have obtained. And we conclude bay providing some reflections on the cultural and historical evaluation of the archaeological records from the Tetouan region in the Middle and the Upper Palaeolithic phases.Les résultats et les conclusions de cet article ont été obtenus grâce aux études qui ont été réalisées dans le cadre de la coopération scientifique internationale qui a permis le développement des projets de recherches archéologiques durant les quinze dernières années et qu’on peut résumer comme suit : • Les matières premières dans la préhistoire du détroit de Gibraltar. Code A/2893/05. Entités participantes : Université de Cadix (Espagne) et Université Abdelmalek Essaâdi (Maroc). Durée, de janvier 2006 à décembre 2006. Chercheurs responsables : Salvador Domínguez-Bella et Ali Maate. • Etude des collections du Musée Archéologique de Tétouan (I). Début de l’inventaire général et de l’analyse de certaines collections thématiques. Code : A/6867/06. Entités participantes : Université de Cadix (Espagne), Institut National des Sciences de l’Archéologie et du Patrimoine (Rabat) et Université Abdelmalek Esaâdi (Tanger-Tétouan) (Maroc). Durée, de janvier 2007 à décembre 2007. Chercheurs responsables : Mehdi Zouak et José Ramos-Muñoz. • Les matières premières dans la Préhistoire du détroit de Gibraltar. Code A/6317/06. Entités participantes : Université de Cadix (Espagne) et Université Abdelmalek Essaâdi (Maroc). Durée, de janvier 2007 à décembre 2007. Chercheurs responsables : Salvador Domínguez-Bella et Ali Maate. • Contribution à l’élaboration de la Carte archéologique du Nord du Maroc (Région Tanger-Tétouan). Analyse de faisabilité et conception du projet. Code A/5790/06. Entités participantes : Université de Cadix (Espagne) et Université Abdelmalek Esaâdi (Tanger-Tétouan, Maroc). Durée, de janvier 2007 à décembre 2007. Chercheurs responsables : Darío Bernal et Baraka Raissounni. • Étude des collections du Musée Archéologique de Tétouan (II). Début de l’inventaire général et de l’analyse de certaines collections thématiques. Code A/010823/07. Entités participantes : Université de Cadix (Espagne), Institut National des Sciences de l’Archéologie et du Patrimoine (Rabat) et Université Abdelmalek Essaâdi (Maroc). Durée, de janvier 2008 à décembre 2008. Chercheurs responsables : José Ramos-Muñoz. et Mehdi Zouak. • Proposition pour le remodelage du contenu du Musée Archéologique de Tétouan. Code AP/040139/11. Entités participantes : Université Abdelmalek Esaâdi (Tanger-Tétouan) (Maroc) et Université de Cadix (Espagne). Durée, de janvier 2012 à décembre 2012. Chercheurs responsables : José Ramos-Muñoz. et Ali Maate. • Projet Carte Archéologique du Nord du Maroc. Région de Tanger-Tétouan. Codes : DRCTT/08/328 ; DRCTT/09/267 ; DRCTT/ ; DRCTT/09/279 ; DRCTT/10/314, DRCTT/11/106, IRMHS-TT/12-48, IRMHS-TT/459/12, 0-094-2011 (BOE 314, 30-12-2011). Organismes de financement : AECID, Junta de Andalucía (Groupe PAI-HUM-440), Université de Cadix (Espagne). Entités participantes : Institut Nacional des Sciences de l’Archéologie et du Patrimoine (Rabat), Université Abdelmalek Esaâdi (Tanger-Tétouan) (Maroc) et Université de Cadix (Espagne). Durée, de janvier 2008 à décembre 2012. Chercheurs responsables : Mehdi Zouak, Abdelaziz El Khayari, Baraka Raissouni, Darío Bernal-Casasola et José Ramos-Muñoz. • Convention de collaboration pour la création du Laboratoire d’Archéologie et du Patrimoine Meknassi de la Région Tanger-Tétouan et le développement de la recherche archéologique et patrimoniale. Entités participantes : Université Abdelmalek Essaâdi, Université de Cadix et Direction Régionale de la Culture de la Région Tanger-Tétouan. Durée : du 24 mai 2012 au 24 mai 2017. Chercheurs responsables : Mehdi Zouak, Darío Bernal, José Ramos-Muñoz., Baraka Raissouni, Mostapha Ghottes et Tarek Moujoud. • Análisis de sociedades prehistóricas del Paleolítico Medio al Neolítico Final en las dos orillas del Estrecho de Gibraltar. Relaciones y contactos -HAR2017-8734P- (Ministerio de Economía, Industria y Competitividad -Agencia Estatal de Investigación, co financé par les fonds FEDER. Chercheurs responsables : José Ramos-Muñoz. et Salvador Domínguez-Bella. Nous tennons donc à remercier tous les chercheurs, les experts et les entités scientifiques, financières et administratives, qui ont permis la réalisation de ces projets de recherches archéologiques de 2005 à 2020

Maritime-oriented foragers during the Late Pleistocene on the eastern costa del sol (Southeast Iberia): Cueva Victoria (Málaga, Spain)

The Mediterranean coast of Spain is marked by several clusters of Palaeolithic sites: to the south of the Pyrenees, in the area around the Ebro River, in the central part, and on the south coast, one of the southernmost regions in Europe. The number of sites is small compared with northern Iberia, but like that region, the Palaeolithic occupations are accompanied by several rock art ensembles. The archaeological material (both biotic and abiotic resources) and radiocarbon dates presented here were obtained during archaeological fieldwork of professor J. Fortea in the Late Pleistocene deposits in Cueva Victoria, located near the modern coastline and about 150 km north of the Strait of Gibraltar. In the three occupation phases, marine resources were acquired by shell-fishing (focusing almost exclusively on the clam Ruditapes decussatus), fishing, and the use of beached marine mammals. This contrasts with the limited data about the exploitation of terrestrial resources by hunting and gathering animals and plants. The study is completed by the study of artefacts (lithic and bone industry and objects of adornment) that help to understand the subsistence strategies of the cave occupants and enable a comparison with other groups inhabiting the Mediterranean coasts of the Iberian Peninsula during Greenland Interstadial 1, between ca. 15.1 and 13.6 cal BP.This work was supported by the University of Salamanca GIR PREHUSAL, the Ministry of Science and Innovation-Spanish Government (PaleontheMove-PID2020-114462GB-I00), the Universidad Nacional de Educación a Distancia (Madrid) and Dirección General de Universitat, Investigacio i Ciencia of the Valencian Regional Government (Project Aico/2020/97).Peer reviewe

The genetic interaction network of CCW12, a Saccharomyces cerevisiae gene required for cell wall integrity during budding and formation of mating projections

<p>Abstract</p> <p>Background</p> <p>Mannoproteins construct the outer cover of the fungal cell wall. The covalently linked cell wall protein Ccw12p is an abundant mannoprotein. It is considered as crucial structural cell wall component since in baker's yeast the lack of <it>CCW12 </it>results in severe cell wall damage and reduced mating efficiency.</p> <p>Results</p> <p>In order to explore the function of <it>CCW12</it>, we performed a Synthetic Genetic Analysis (SGA) and identified genes that are essential in the absence of <it>CCW12</it>. The resulting interaction network identified 21 genes involved in cell wall integrity, chitin synthesis, cell polarity, vesicular transport and endocytosis. Among those are <it>PFD1</it>, <it>WHI3</it>, <it>SRN2</it>, <it>PAC10</it>, <it>FEN1 </it>and <it>YDR417C</it>, which have not been related to cell wall integrity before. We correlated our results with genetic interaction networks of genes involved in glucan and chitin synthesis. A core of genes essential to maintain cell integrity in response to cell wall stress was identified. In addition, we performed a large-scale transcriptional analysis and compared the transcriptional changes observed in mutant <it>ccw12</it>Δ with transcriptomes from studies investigating responses to constitutive or acute cell wall damage. We identified a set of genes that are highly induced in the majority of the mutants/conditions and are directly related to the cell wall integrity pathway and cell wall compensatory responses. Among those are <it>BCK1</it>, <it>CHS3</it>, <it>EDE1</it>, <it>PFD1</it>, <it>SLT2 </it>and <it>SLA1 </it>that were also identified in the SGA. In contrast, a specific feature of mutant <it>ccw12</it>Δ is the transcriptional repression of genes involved in mating. Physiological experiments substantiate this finding. Further, we demonstrate that Ccw12p is present at the cell periphery and highly concentrated at the presumptive budding site, around the bud, at the septum and at the tip of the mating projection.</p> <p>Conclusions</p> <p>The combination of high throughput screenings, phenotypic analyses and localization studies provides new insight into the function of Ccw12p. A compensatory response, culminating in cell wall remodelling and transport/recycling pathways is required to buffer the loss of <it>CCW12</it>. Moreover, the enrichment of Ccw12p in bud, septum and mating projection is consistent with a role of Ccw12p in preserving cell wall integrity at sites of active growth.</p> <p>The microarray data produced in this analysis have been submitted to NCBI GEO database and GSE22649 record was assigned.</p

Secuenciación y análisis de 14 fases de lectura abierta en los cromosomas XI y XIV de "Saccharomyces cerevisiae"

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 22-04-199