The lead and copper isotopic composition of copper ores from the Sierra Morena (Spain)

The paper presents lead and copper isotope analyses of 51 copper ore samples from the Sierra Morena, South of Spain. They are from ancient mines of the Iberian Peninsula collected by Claude Domergue during various field campaigns in the central Sierra Morena from 1965 to 1975. Most samples consist of copper oxide minerals such as malachite, azurite and chrysocolla and stem from the surficial sections of the ore deposits. The aim of the study was to supplement the existing reference data bank on lead isotopic compositions of ancient copper mines from the Iberian Peninsula. This is particularly important for the Sierra Morena for which data exist mostly for lead-zinc but not for copper ores. The lead isotope ratios range from 18.165 to 19.712 (206Pb/204Pb), 0.797 to 0.859 (207Pb/206Pb) and 1.955 to 2.108 (208Pb/206Pb). Two separate fields can be distinguished with a major field intermediate between the ore deposits from SW and SE Spain and a second at higher 208Pb/206Pb values. Copper isotopes were analysed additionally to provide further constraints for provenance studies. The copper isotope ratios δ65Cu of the copper oxide samples are mostly positive and higher on average than those of sulphide minerals. They are a potential tool to distinguish between either sulphide ore or oxide ore deposit derived artefacts.En este artículo, presentamos los resultados de los análisis isotópicos (plomo y cobre) llevados a cabo sobre 51 muestras de mineral de cobre de Sierra Morena, Sur de España. Las muestras provienen de minas antiguas de la Península Ibérica, que habían sido recogidas por Claude Domergue en el curso de sus prospecciones en Sierra Morena central, entre 1965 y 1975. La mayoría de las muestras consiste de minerales de óxido de cobre como malaquita, azurita y crisocola que se encuentran en la superficie de los depósitos. El objetivo de este estudio es de contribuir a la base hoy disponible de datos de isótopos de plomo de las antiguas minas de cobre en la Península Ibérica. Este objetivo es particularmente importante puesto que la mayoría de los datos publicados de Sierra Morena se refieren a minerales de plomo-zinc. Las proporciones de isótopos de plomo varían entre 18.165 y 19.713 206Pb/204Pb, de 0.797 a 0.859 207Pb/206Pb, y de 1.955 a 2.108 208Pb/206Pb. Se pueden distinguir dos zonas independientes: una zona principal que se sitúa entre los depósitos de España del sudoeste y sudeste y una segunda zona con las proporciones de isótopos de plomo más altas. Además, los isótopos del cobre fueron analizados para suplir restricciones adicionales en los estudios de proveniencia. Las proporciones de isótopos de cobre, δ65Cu/63Cu, fueron analizadas en los óxidos de cobre y son en la mayor parte positivas y mas altas en medio que las proporciones δ65Cu de los sulfuros de cobre. Los resultados presentan un instrumento eficiente para distinguir los artefactos elaborados de minerales de sulfuros de cobre o de minerales de óxido de cobre

The Arabidopsis cer26 mutant, like the cer2 mutant, is specifically affected in the very long chain fatty acid elongation process

Plant aerial organs are covered by cuticular waxes, which form a hydrophobic crystal layer that mainly serves as a waterproof barrier. Cuticular wax is a complex mixture of very long chain lipids deriving from fatty acids, predominantly of chain lengths from 26 to 34 carbons, which result from acyl-CoA elongase activity. The biochemical mechanism of elongation is well characterized; however, little is known about the specific proteins involved in the elongation of compounds with more than 26 carbons available as precursors of wax synthesis. In this context, we characterized the three Arabidopsis genes of the CER2-like family: CER2, CER26 and CER26-like . Expression pattern analysis showed that the three genes are differentially expressed in an organ- and tissue-specific manner. Using individual TDNA insertion mutants, together with a cer2 cer26 double mutant, we characterized the specific impact of the inactivation of the different genes on cuticular waxes. In particular, whereas the cer2 mutation impaired the production of wax components longer than 28 carbons, the cer26 mutant was found to be affected in the production of wax components longer than 30 carbons. The analysis of the acyl-CoA pool in the respective transgenic lines confirmed that inactivation of both genes specifically affects the fatty acid elongation process beyond 26 carbons. Furthermore, ectopic expression of CER26 in transgenic plants demonstrates that CER26 facilitates the elongation of the very long chain fatty acids of 30 carbons or more, with high tissular and substrate specificity

Contribution of CgPDR1-Regulated Genes in Enhanced Virulence of Azole-Resistant Candida glabrata

In Candida glabrata, the transcription factor CgPdr1 is involved in resistance to azole antifungals via upregulation of ATP binding cassette (ABC)-transporter genes including at least CgCDR1, CgCDR2 and CgSNQ2. A high diversity of GOF (gain-of-function) mutations in CgPDR1 exists for the upregulation of ABC-transporters. These mutations enhance C. glabrata virulence in animal models, thus indicating that CgPDR1 might regulate the expression of yet unidentified virulence factors. We hypothesized that CgPdr1-dependent virulence factor(s) should be commonly regulated by all GOF mutations in CgPDR1. As deduced from transcript profiling with microarrays, a high number of genes (up to 385) were differentially regulated by a selected number (7) of GOF mutations expressed in the same genetic background. Surprisingly, the transcriptional profiles resulting from expression of GOF mutations showed minimal overlap in co-regulated genes. Only two genes, CgCDR1 and PUP1 (for PDR1 upregulated and encoding a mitochondrial protein), were commonly upregulated by all tested GOFs. While both genes mediated azole resistance, although to different extents, their deletions in an azole-resistant isolate led to a reduction of virulence and decreased tissue burden as compared to clinical parents. As expected from their role in C. glabrata virulence, the two genes were expressed as well in vitro and in vivo. The individual overexpression of these two genes in a CgPDR1-independent manner could partially restore phenotypes obtained in clinical isolates. These data therefore demonstrate that at least these two CgPDR1-dependent and -upregulated genes contribute to the enhanced virulence of C. glabrata that acquired azole resistance

The BET bromodomain inhibitor I-BET-151 induces structural and functional alterations of the heart mitochondria in healthy male mice and rats

The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications

SHINE Transcription Factors Act Redundantly to Pattern the Archetypal Surface of Arabidopsis Flower Organs

Floral organs display tremendous variation in their exterior that is essential for organogenesis and the interaction with the environment. This diversity in surface characteristics is largely dependent on the composition and structure of their coating cuticular layer. To date, mechanisms of flower organ initiation and identity have been studied extensively, while little is known regarding the regulation of flower organs surface formation, cuticle composition, and its developmental significance. Using a synthetic microRNA approach to simultaneously silence the three SHINE (SHN) clade members, we revealed that these transcription factors act redundantly to shape the surface and morphology of Arabidopsis flowers. It appears that SHNs regulate floral organs' epidermal cell elongation and decoration with nanoridges, particularly in petals. Reduced activity of SHN transcription factors results in floral organs' fusion and earlier abscission that is accompanied by a decrease in cutin load and modified cell wall properties. SHN transcription factors possess target genes within four cutin- and suberin-associated protein families including, CYP86A cytochrome P450s, fatty acyl-CoA reductases, GSDL-motif lipases, and BODYGUARD1-like proteins. The results suggest that alongside controlling cuticular lipids metabolism, SHNs act to modify the epidermis cell wall through altering pectin metabolism and structural proteins. We also provide evidence that surface formation in petals and other floral organs during their growth and elongation or in abscission and dehiscence through SHNs is partially mediated by gibberellin and the DELLA signaling cascade. This study therefore demonstrates the need for a defined composition and structure of the cuticle and cell wall in order to form the archetypal features of floral organs surfaces and control their cell-to-cell separation processes. Furthermore, it will promote future investigation into the relation between the regulation of organ surface patterning and the broader control of flower development and biological functions

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

The Set3/Hos2 Histone Deacetylase Complex Attenuates cAMP/PKA Signaling to Regulate Morphogenesis and Virulence of Candida albicans

Candida albicans, like other pleiomorphic fungal pathogens, is able to undergo a reversible transition between single yeast-like cells and multicellular filaments. This morphogenetic process has long been considered as a key fungal virulence factor. Here, we identify the evolutionarily conserved Set3/Hos2 histone deacetylase complex (Set3C) as a crucial repressor of the yeast-to-filament transition. Cells lacking core components of the Set3C are able to maintain all developmental phases, but are hypersusceptible to filamentation-inducing signals, because of a hyperactive cAMP/Protein Kinase A signaling pathway. Strikingly, Set3C-mediated control of filamentation is required for virulence in vivo, since set3Δ/Δ cells display strongly attenuated virulence in a mouse model of systemic infection. Importantly, the inhibition of histone deacetylase activity by trichostatin A exclusively phenocopies the absence of a functional Set3C, but not of any other histone deacetylase gene. Hence, our work supports a paradigm for manipulating morphogenesis in C. albicans through alternative antifungal therapeutic strategies

Una inscripción de época republicana dedicada a <i>Salaecus</i> en la región minera de Carthago Nova

In this paper we study an unpublished votive inscription from Mina Mercurio (in Portman, Cartagena), exhibited at the Aguilas Archaeological Museum. It is dedicated by freedmen from the <i>gens Roscia</i>, a well-known family of negotiators who used to sign the argentiferous galena ingot hallmark found in Cabezo Rajao in La Unión around 1846. It is one of the oldest inscriptions found in the area of <i>Carthago Noua</i>, and thus, in the whole Hispania. It is dated at the end of the 2nd century or very beginning of the 1st century b.c., especially with the use of an archaic plural nominative in -es. It is dedicated to <i>Salaecus</i>, a vocative etymologically related to water and the sea. For this reason and because of the place where it was found, it might refer to the Roman god Neptune or to a Hispanic deity related to water.<br><br>Estudiamos una inscripción votiva inédita procedente de Mina Mercurio (Portmán, Cartagena), depositada en el Museo Arqueológico de Águilas. La dedican unos libertos de la <i>gens Roscia</i>, conocida familia de <i>negotiatores</i> que firmaban los sellos de lingotes de galena argentífera que aparecieron en el Cabezo Rajao de La Unión, en torno a 1846. Se trata de una de las inscripciones más antiguas de la zona de <i>Carthago Noua</i>. Se fecha a finales del siglo II o principios del siglo I a. C., fundamentalmente a partir de la utilización de un nominativo plural arcaico en <i>-es</i>. Está dedicada a <i>Salaecus</i>, un apelativo que se relaciona etimológicamente con las aguas y con el mar. Por ello y por el lugar donde apareció, formulamos la hipótesis de que haría alusión al dios romano Neptuno o a una deidad hispánica relacionada con el agua

Production of very long chain polyunsaturated omega-3 and omega-6 fatty acids in plants

We report the production of two very long chain polyunsaturated fatty acids, arachidonic acid (AA) and eicosapentaenoic acid (EPA), in substantial quantities in a higher plant. This was achieved using genes encoding enzymes participating in the ω3/6 Δ8-desaturation biosynthetic pathways for the formation of C20 polyunsaturated fatty acids. Arabidopsis thaliana was transformed sequentially with genes encoding a Δ9-specific elongating activity from Isochrysis galbana, a Δ8-desaturase from Euglena gracilis and a Δ5-desaturase from Mortierella alpina. Instrumental in the successful reconstitution of these C20 polyunsaturated fatty acid biosynthetic pathways was the I. galbana C18-Δ9-elongating activity, which may bypass rate-limiting steps present in the conventional Δ6-desaturase/elongase pathways. The accumulation of EPA and AA in transgenic plants is a breakthrough in the search for alternative sustainable sources of fish oils.&nbsp