Material flow analysis for identifying rare earth element recycling potentials in the EU-27

International audienceRare earth elements (REEs) are essential for high-techology industrial sectors. This paper presents research on material flow analysis (MFA) applied to REEs in the EU-27. Innovative aspects of this research pertain to (i) considering potential lithospheric stocks of REEs in the EU and (ii) accounting for incomplete and imprecise information in MFA data reconciliation. Results obtained to-date provides a history of EU-27 raw rare earth imports and exports and a methodology for data reconciliation which constitutes an alternative to the classical least-squares method

Phenotypic and genotypic characterization of imipenem-resistant Pseudomonas aeruginosa isolated in Buenos Aires

En el presente estudio, que tuvo por objeto analizar los mecanismos involucrados en la resistencia a carbapenemes, se incluyeron 129 aislamientos de Pseudomonas aeruginosa recuperados durante el año 2006 en el Hospital “Eva Perón” de la Provincia de Buenos Aires. La caracterización fenotípica y genotípica de la resistencia permitió reconocer la presencia de metalo-β-lactamasas (MBL) en el 14% de esos aislamientos. En todos ellos se identificó la presencia de la enzima IMP-13; sin embargo, algunos aislamientos resultaron sensibles a carbapenemes de acuerdo a los puntos de corte establecidos por el CLSI e incluso a las sugerencias de la Subcomisión de Antimicrobianos de SADEBAC, AAM. El ensayo de detección fenotípica de MBL de sinergia con doble disco resultó útil en este estudio. Sólo aquellos aislamientos productores de IMP-13 que a su vez presentaron alteraciones en las proteínas de membrana externa resultaron completamente resistentes a imipenem. Los aislamientos productores de MBL correspondieron a varios tipos clonales, lo cual sugiere no sólo la diseminación de una cepa resistente, sino también la diseminación horizontal de este mecanismo de resistencia entre clones diferentesrom 129 P. aeruginosa isolated at a health care centre located in Buenos Aires (Hospital “Eva Perón”), 14% produced IMP-13. Although 18 isolates were metallo-β-lactamases (MBL) producers, only those isolates that displayed altered outer membrane protein profiles correlated with the resistant category according to CLSI or even Subcomisión de Antimicrobianos, SADEBAC, AAM. Phenotypic screening of metallo-β-lactamases proved to be appropriate for detecting MBL producing isolates. IMP-13 producing isolates corresponded to at least five different clonal types, which not only suggests the dissemination of the resistant strain but also of the resistant marker.Fil: Cejas, D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Almuzara, Marisa. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Santella, G.. Universidad de Buenos Aires; ArgentinaFil: Tuduri, A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón". Servicio de Neurología; ArgentinaFil: Palombarani, Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Figueroa, S.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón". Servicio de Neurología; ArgentinaFil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Radice, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Role of transcript and interplay between transcription and replication in triplet-repeat instability in mammalian cells

Triplet-repeat expansions cause several inherited human diseases. Expanded triplet-repeats are unstable in somatic cells, and tissue-specific somatic instability contributes to disease pathogenesis. In mammalian cells instability of triplet-repeats is dependent on the location of the origin of replication relative to the repeat tract, supporting the ‘fork-shift’ model of repeat instability. Disease-causing triplet-repeats are transcribed, but how this influences instability remains unclear. We examined instability of the expanded (GAA•TTC)n sequence in mammalian cells by analyzing individual replication events directed by the SV40 origin from five different locations, in the presence and absence of doxycycline-induced transcription. Depending on the location of the SV40 origin, either no instability was observed, instability was caused by replication with no further increase due to transcription, or instability required transcription. Whereas contractions accounted for most of the observed instability, one construct showed expansions upon induction of transcription. These expansions disappeared when transcript stability was reduced via removal or mutation of a spliceable intron. These results reveal a complex interrelationship of transcription and replication in the etiology of repeat instability. While both processes may not be sufficient for the initiation of instability, transcription and/or transcript stability seem to further modulate the fork-shift model of triplet-repeat instability

Inhibitory Effects of Leptin on Pancreatic α-Cell Function

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE-Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in a-cell function has not been studied in detail. In the present study, we have investigated this functional interaction. RESEARCH DESIGN AND METHODS-The presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp and Ca(2+) signals by confocal microscopy. Exocytosis and glucagon secretion were assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS-The expression of several ObR isoforms (a-e) was detected in glucagon-secreting alpha TC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in alpha TC1-9 cells as well as in mouse and human alpha-cells. The application of leptin (6.25 nmol/l) hyperpolarized the alpha-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l glucose. Additionally, leptin inhibited Ca(2+) signaling in alpha TC1-9 cells and in mouse and human alpha-cells within intact islets. A similar result occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and were counteracted by the phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement of this pathway in leptin action. CONCLUSIONS-These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipo-insular communication. Diabetes 58:1616-1624, 200958716161624Ministerio de Educacion y Ciencia [BFU2007-67607, PCI2005-A7-0131, BFU2008-01492, SAF2006-07382]Ministerio de Ciencia a InnovacionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Ministerio de Educacion y Ciencia [BFU2007-67607, PCI2005-A7-0131, BFU2008-01492, SAF2006-07382]FAPESP [2008/53811-8

Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX

THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO in these processes is uncertain, which suggests a differential implication of mRNP biogenesis factors in genome integrity in yeast and humans. We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and γH2AX and 53BP1 foci accumulation. This is accompanied by replication alteration as determined by DNA combing. Genome instability is R-loop–dependent, as deduced from the ability of the AID enzyme to increase DNA damage and of RNaseH to reduce it, or from the enhancement of R-loop–dependent class-switching caused by THOC1-depletion in CH12 murine cells. Therefore, mammalian THO prevents R-loop formation and has a role in genome dynamics and function consistent with an evolutionary conservation of the functional connection between these mRNP biogenesis factors and genome integrity that had not been anticipated

Innovative tools and modeling methodology for impact prediction and assessment of the contribution of materials on indoor air quality

International audienceBackground: The combination of more and more airtight buildings and the emission of formaldehyde and other volatile organic compounds (VOCs) by building, decoration and furniture materials lead to lower indoor air quality. Hence, it is an important challenge for public health but also for the preservation of cultural heritage, as for example, artworks in museum showcases and other cultural objects. Indeed, some VOCs such as organic acids or carbonyl compounds may play a role in the degradation of some metallic objects or historic papers. Thus, simple and cost effective sampling tools are required to meet the recent and growing demand of on-site diagnostic of indoor air quality , including emission source identification and their ranking.Results: In this aim, we developed new tools based on passive sampling (Solid-Phase Micro Extraction, SPME) to measure carbonyls compounds (including formaldehyde) and other VOCs and both in indoor air and at the material/ air interface. On one hand, the coupling of SPME with a specially designed emission cell allows the screening and the quantification of the VOCs emitted by building, decoration or furniture materials. On the other hand, indoor air is simply analysed using new vacuum vial sampling combined with VOCs pre-concentration by SPME. These alternative sampling methods are energy free, compact, silent and easy to implement for on-site measurements. They show satisfactory analytical performance as detection limits range from 0.05 to 0.1 µg m −3 with an average Relative Standard Deviation (RSD) of 18 %. They already have been applied to monitoring of indoor air quality and building material emissions for a 6 months period. The data obtained were in agreement with the prediction of a physical monozonal model which considers building materials both as VOC sources and sinks and air exchange rate in one single room ("box model").Conclusion: Results are promising, even if more data are required to complete validation, and the model could be envisaged as a predictive tool for indoor air quality. This new integrated approach involving measurements and mod-eling could be easily transposed to historic environments and to the preservation of cultural heritage

The SR Protein B52/SRp55 Is Required for DNA Topoisomerase I Recruitment to Chromatin, mRNA Release and Transcription Shutdown

DNA- and RNA-processing pathways are integrated and interconnected in the eukaryotic nucleus to allow efficient gene expression and to maintain genomic stability. The recruitment of DNA Topoisomerase I (Topo I), an enzyme controlling DNA supercoiling and acting as a specific kinase for the SR-protein family of splicing factors, to highly transcribed loci represents a mechanism by which transcription and processing can be coordinated and genomic instability avoided. Here we show that Drosophila Topo I associates with and phosphorylates the SR protein B52. Surprisingly, expression of a high-affinity binding site for B52 in transgenic flies restricted localization, not only of B52, but also of Topo I to this single transcription site, whereas B52 RNAi knockdown induced mis-localization of Topo I in the nucleolus. Impaired delivery of Topo I to a heat shock gene caused retention of the mRNA at its site of transcription and delayed gene deactivation after heat shock. Our data show that B52 delivers Topo I to RNA polymerase II-active chromatin loci and provide the first evidence that DNA topology and mRNA release can be coordinated to control gene expression

Increased cortical surface area and gyrification following long-term survival from early monocular enucleation

AbstractPurposeRetinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation.MethodsNine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined.ResultsEarly monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation.ConclusionsAltered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss