Evidence of an efflux pump in Serratia marcescens

Spontaneous mutants resistant to fluoroquinolones were obtained by exposing Serratia marcescens NIMA (wild-type strain) to increasing concentrations of ciprofloxacin both in liquid and on solid media. Frequencies of mutation ranged from 10-7 to 10-9. Active expulsion of antibiotic was explored as a possible mechanism of resistance in mutants as well as changes in topoisomerase target genes. The role of extrusion mechanisms in determining the emergence of multidrug-resistant bacteria was also examined. Mutants resistant to high concentrations of fluoroquinolones had a single mutation in their gyrA QRDR sequences, whereas the moderate resistance in the rest of mutants was due to extrusion of the drug

Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin-clavulanate and ceftriaxone

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of penicillin ≥2 µg/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance

Gallery districts of Barcelona: the strategic play of art dealers

This article focuses on Barcelona"s art market to explore the underlying factors behind the clustering of art dealers in several of the city"s districts. Drawing upon quantitative and qualitative data, the article analyses how such clustering reveals a strategic action in the sense attributed to it by Crozier and Friedberg (1981). Gallery districts are not a reflection of structural factors (economic, urban development-related or social) but the result of a combination of strategic choices either individual or collective which explain the permanence of leading gallery districts or the emergence of new ones.

Exploration of the social dimension of corporate responsibility in a welfare state

This study focuses on corporate social responsibility (or CSR)as the latest dimension to emerge in the corporate responsibility and sustainability agenda, which in the recent past has rapidly risen to the top of the list of concerns for civil societies worldwide. Despite the continuing debates and discussions about the scope, benefits, and impacts of CSR to business and community in various sectors, levels, and types of society, many companies have moved forward to confront the opportunities and challenges of CSR. Thus, this study is about those proactive companies with a focus on the importance of CSR and its management inside and outside the company. It is an exploration and learning from the experience of Finnish companies, as well as other actors interested or involved in shaping the course of CSR, locally and globally. It also looks closely at how national culture affects the views, thinking, and management of CSR in a welfare state. This dissertation primarily draws on the analyses of information collected from a series of qualitative interviews and the existing literature in the area. This is complemented by an analysis of written and published documents on CSR from various sources. The results of the study give insightful information and detailed descriptions of a roadmap useful in learning and understanding CSR in Finnish companies. Despite the varying conceptual connotations, essential roadmap indicators point to the importance of framing CSR within the corporate responsibility concept, Finnish development and the welfare state system, globalization, stakeholders, and the pursuit of sustainable development as the main drivers of CSR, the remarkable progress of CSR in companies, and identification of key management areas and practices relevant to CSR. Similarly,the study reveals the importance of culture as essential in understanding and learning CSR. Finnish culture has a positive influence on the views, thinking, and management practices of CSR issues. Such a positive influence of culture, therefore, makes it easy for business people to discuss and understand CSR, because those CSR issues are already considered common and taken-for-granted by Finns and are implicit in the welfare state provisions. The experience of Finnish companies in implementing CSR policies in the supply chain is a concrete proactive step in advancing the message of CSR, that is, to bring companies and suppliers together to work on improving and strengthening relationships towards socially responsible practices worldwide. Such a forward step to deal with CSR issues in the supply chain reflects the companies' commitments and belief that CSR can be managed with the suppliers and gain positive benefits. Despite the problems and complexities, particularly in the global supply chain, managing CSR for Finnish companies presents new opportunities and challenges that are expected to intensify in the near future. The focus on CSR policy implementation inthe supply chain points to the importance of companies taking initiatives and forging cooperation with suppliers with the aim of addressing and improving CSR questions in the supply chains. The proactive stance of Finnish companies toward CSR is complemented by the active supporting role of important societalactors such as the government and NGOs. These actors carry out various promotional efforts and campaigns, thus bringing CSR into the mainstream of Finnish companies and strengthening the synergistic learning about CSR within the Finnish business and civil circles. The efforts of the government and NGOs to promote CSR are indicative of the importance of multipartite involvement and the emergence of better civil regulations. Likewise, their drive to learn from each other, exchange experiences, and contribute in CSR debates facilitated the evolution of CSRnetworks in the country. The results of this study add to the mounting evidence that CSR, in general, has created a new dimension in managing corporate sustainability. This study provides compelling empirical evidence and some direct quotations about CSR in the Finnish context. This information can be used to learn and gain new useful insights, approaches, and concepts for managing CSR.

A germination study of herbicide-resistant field poppies in Spain

Field poppy, Papaver rhoeas L., is a very common weed in winter cereals in North-Eastern Spain. Its control is becoming difficult due to expanding herbicide resistance. To control field poppies there are alternative strategies such as non-chemical control that take into account the weed emergence period. However, there is a lack of knowledge of P. rhoeas emergence patterns in semi-arid conditions. Thus, here we conducted pot experiments on the emergence of P. rhoeas. We aimed to describe the emergence period and to quantify the emergence of a susceptible and of a herbicide-resistant P. rhoeas population at two locations in Catalonia, Spain, from 1998 to 2001 and until 2004 at one of them. Therefore, pots containing seeds of both populations were established at the two locations and emergence was recorded monthly. We studied the origin of the population, the sowing location, the effect of cultivation and the sowing year. First, we found that the main emergence peaks in our experiments occurred in autumn, accounting for between 65.7 and 98.5% of the annual emergence from October to December, and only little emergence was recorded in spring. This emergence pattern is different from those found in the literature corresponding to Northern European countries, where in some cases main flushes occur only in autumn, in spring and winter or only in spring. The emergence was mainly affected by cultivation, but the effect of light stimulus was observed several months later. As a consequence, cultivation should be done in early autumn, promoting emergence during the whole autumn and winter so that emerged seedlings can be controlled before sowing a spring crop. Second, most experiments showed that the emergence was significantly higher in the first autumn than in the following seasons, e.g. 4.1% emergence in the first year and only 2.1, 2.3, 0.5 and 0.6% new emergence at one of the locations for the second, third, fourth and fifth years. Thus, after having a severe P. rhoeas infestation causing a big seed rain, emergence should be stimulated by autumn cultivation in the following season and seedlings controlled by trying to deplete the soil seed bank as much as possible. Despite the fact that emergence will be staggered throughout several years and that there was a significant relationship between rainfall and emergence, so that dry years will cause a smaller emergence rate of the weed, these findings define a cultural management strategy to reduce P. rhoeas infestations and to contribute to integrated weed management strategies combining it with other tools.

Barley development as affected by rate of change of photoperiod

The rate of leaf appearance of barley varies substantially with time of sowing. This variation has been related to both the length and the rate of change of photoperiod at the time of plant emergence. An outdoor pot experiment was conducted to test if rate of change of photoperiod directly affects phasic development and rate of leaf emergence of spring barley. Two photoperiod-sensitive cultivars (Bandulla and Galleon) were subjected to five photoperiod regimes: two constant photoperiods, of 14 and 15·5 h, and three different rates of change of photoperiod of c. 2, 9 and 13 min/day from seedling emergence to awn initiation. Photoperiod treatments significantly affected the duration from seedling emergence to awn initiation in both cultivars. Rate of change of photoperiod did not affect the rate of development towards awn initiation independently of the absolute daylength it produced. Although Bandulla had a longer duration than Galleon at any photoperiod regime, the cultivars did not vary in their sensitivity to photoperiod. When this phase was divided into the leaf initiation (LI) and spikelet initiation (SI) phases, it was evident that the sensitivity to photoperiod was not constant, being in general higher during the SI than during the LI phase. However, the magnitude of the change in sensitivity was cultivar-dependent, indicating that sensitivity to photoperiod during the different phases could be under independent genetic control. Final numbers of primordia (leaves together with maximum spikelet number) were negatively affected by increasing photoperiods, but once again, there was no evidence of any effect of the rate of change of photoperiod which was independent of the average photoperiod. Both cultivars showed similar sensitivities for final leaf number but maximum spikelet number was more sensitive to photoperiod in Galleon than in Bandulla. Highly significant linear relationships between leaf number and thermal time were found for all combinations of cultivars and photoperiod regimes (r2 > 0·98). The rate of leaf appearance (RLA) was similar for both cultivars (c. 0·0185 leaves/°Cd) and did not alter during plant development or in response to the change in photoperiod at awn initiation. The range in RLA was greater for Galleon (0·0170–0·0205 leaves/°Cd) than for Bandulla (0·0173–0·0186 leaves/°Cd). Neither of these cultivars exhibited a significant relationship between rate of leaf emergence and photoperiod or rate of change of photoperiod. The lack of significant relationships between RLA and length or rate of change of photoperiod is in contrast with previous reports using time of sowing as a main treatment.

The political ecology of ecosystem services

The dominance of ''ecosystem services'' as a guiding concept for environmental management - where it appears as a neutral, obvious, taken-for-granted concept - hides the fact that there are choices implicit in its framing and in its application. In other words, it is a highly political concept, and its utility depends on the arena in which it is used and what it is used for. Following a political ecology framework, and based on a literature review, bibliometric analyses, and brief examples from two tropical rainforest countries, this review investigates four moments in the construction and application of the ecosystem services idea: socio-historical (the emergence of the discourse), ontological (what knowledge does the concept allow?), scientific (difficulties in its practical application), and political (who wins, who loses?). We show how the concept is a boundary object with widespread appeal, trace the discursive and institutional context within which it gained traction, and argue that choices of scale, definition, and method in measuring ecosystem services frustrate its straightforward application. As a result, it is used in diverse ways by dif- ferent interests to justify different kinds of interventions that at times might be totally opposed. In Madagascar, the ecosystem services idea is mainly used to justify forest conservation in ways open to cri- tique for its neoliberalization of nature or disempowerment of communities. In contrast, in the Brazilian Amazon, the discourse of ecosystem services has served the agendas of traditional populations and family farm lobbies. Ecosystem services, as an idea and tool, are mobilized by diverse actors in real-life situa- tions that lead to complex, regionally particular and fundamentally political outcomes.

Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells.

BACKGROUND: Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4',6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays. RESULTS: The FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 μg/mL and 1.7 μg/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells. CONCLUSION: Our findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs.

Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Use and availability of scholarly journals in Catalan academic libraries

This paper presents the results of a survey of academics affiliated to the universities that are members of the Consortium of Academic Libraries of Catalonia (CBUC) and an analysis of the availability in the libraries of these universities of the references cited in a sample of articles published by these academics. The results reflect the major importance that researchers assign to scholarly journals as the main source of scientific information. Most state that they use electronic journals either exclusively or in any case more than print journals, a preference that is higher among younger scholars. With regard to frequency of reading, four out of ten researchers state that they read journals virtually every day, while nine out of ten report that they do so at least once a week. Scholars claim that the obstacles they face when trying to download an article are related to the lack of subscriptions. However, the availability study showed that most of the articles cited in their publications are available at least at one of the CBUC libraries. Though most researchers keep a copy of the articles they consult, just over a third of them use some kind of reference management software.

From trade to industry. The wine production sector in the Penedès Denomination of Origin, 1940-2000

[cat] Aquest treball té com a objectiu mostrar el grau en què el sector de la producció de vi a la Denominació d'Origen Penedès ha respost als reptes que s’han plantejat tant en termes de l'oferta (de consolidació i sorgiment dels països productors fora de l'esfera europea tradicional) i de la demanda (caiguda de la el consum de vi i els nous hàbits de consum) durant la segona meitat del segle XX. El document analitza l'evolució del sector a la regió des del començament de la dècada de 1940 fins a la fi del segle. Amb la fi de la Guerra Civil de 1936-1939 el sector va haver d'afrontar una caiguda de la producció, la qual va continuar concentrant-se en la comercialització de vins tradicionals. Aquesta situació va canviar quan, a finals de la dècada de 1960, la demanda es va girar cada vegada més als vins de major qualitat embotellats. Des del punt de vista legislatiu, la resposta es va centrar en la innovació tecnològica i la reestructuració de l'empresa. Aquest període va ser testimoni de la introducció de nous equips i processos, com ara l’acer inoxidable i tancs de fermentació a temperatura controlada, amb els vins embotellats expulsant el vi a granel i la transformació dels grans magatzemistes en cellers i caves. A més, una de les principals característiques del període 1970-1985 va ser la formació dels grans conglomerats empresarials dels vins i del cava. L’entrada d'Espanya a la Unió Europea el 1986 va impulsar una acceleració d'aquest procés de transformació, deixant el sector format principalment per empreses que produeixen vins i caves, que han introduït els vins negres i varietals en la seva oferta de productes, que posseeixen moltes hectàrees de vinyes i en molts casos, que han mostrat una clara intenció de penetrar en el mercat internacional.

From trade to industry. The wine production sector in the Penedès Denomination of Origin, 1940-2000

[cat] Aquest treball té com a objectiu mostrar el grau en què el sector de la producció de vi a la Denominació d'Origen Penedès ha respost als reptes que s’han plantejat tant en termes de l'oferta (de consolidació i sorgiment dels països productors fora de l'esfera europea tradicional) i de la demanda (caiguda de la el consum de vi i els nous hàbits de consum) durant la segona meitat del segle XX. El document analitza l'evolució del sector a la regió des del començament de la dècada de 1940 fins a la fi del segle. Amb la fi de la Guerra Civil de 1936-1939 el sector va haver d'afrontar una caiguda de la producció, la qual va continuar concentrant-se en la comercialització de vins tradicionals. Aquesta situació va canviar quan, a finals de la dècada de 1960, la demanda es va girar cada vegada més als vins de major qualitat embotellats. Des del punt de vista legislatiu, la resposta es va centrar en la innovació tecnològica i la reestructuració de l'empresa. Aquest període va ser testimoni de la introducció de nous equips i processos, com ara l’acer inoxidable i tancs de fermentació a temperatura controlada, amb els vins embotellats expulsant el vi a granel i la transformació dels grans magatzemistes en cellers i caves. A més, una de les principals característiques del període 1970-1985 va ser la formació dels grans conglomerats empresarials dels vins i del cava. L’entrada d'Espanya a la Unió Europea el 1986 va impulsar una acceleració d'aquest procés de transformació, deixant el sector format principalment per empreses que produeixen vins i caves, que han introduït els vins negres i varietals en la seva oferta de productes, que posseeixen moltes hectàrees de vinyes i en molts casos, que han mostrat una clara intenció de penetrar en el mercat internacional.

Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species.

OBJECTIVES: Invasive mould infections are associated with a high mortality rate and the emergence of MDR moulds is of particular concern. Calcineurin and its chaperone, the heat shock protein 90 (Hsp90), represent an important pathway for fungal virulence that can be targeted at different levels. We investigated the antifungal activity of compounds directly or indirectly targeting the Hsp90-calcineurin axis against different mould species. METHODS: The in vitro antifungal activity of the anticalcineurin drug FK506 (tacrolimus), the Hsp90 inhibitor geldanamycin, the lysine deacetylase inhibitor trichostatin A and the Hsp70 inhibitor pifithrin-μ was assessed by the standard broth dilution method against 62 clinical isolates of Aspergillus spp. and non-Aspergillus moulds (Mucoromycotina, Fusarium spp., Scedosporium spp., Purpureocillium/Paecilomyces spp. and Scopulariopsis spp.) RESULTS: FK506 had variable antifungal activity against different Aspergillus spp. and was particularly active against Mucor spp. Geldanamycin had moderate antifungal activity against Fusarium spp. and Paecilomyces variotii. Importantly, trichostatin A had good activity against the triazole-resistant Aspergillus ustus and the amphotericin B-resistant Aspergillus terreus as well as the MDR Scedosporium prolificans. Moreover, trichostatin A exhibited synergistic interactions with caspofungin against A. ustus and with geldanamycin against Rhizopus spp. for which none of the other agents showed activity. Pifithrin-μ exhibited little antifungal activity. CONCLUSIONS: Targeting the Hsp90-calcineurin axis at different levels resulted in distinct patterns of susceptibility among different fungal species. Lysine deacetylase inhibition may represent a promising novel antifungal strategy against emerging resistant moulds.

The Outcry of the Periphery? An Analysis of Ticino's No to Immigration

When the popular initiative "against mass immigration" was accepted by the Swiss people and cantons on 9 February 2014, Ticino had by far the highest approval rate. The Italian-speaking canton thus once more confirmed its singular position, assumed since the 1990s, on popular votes regarding immigration and foreign policy. This seems to be indicative of wider crises and changes in both the economic and political spheres that have favoured the emergence of a political opposition between centre and periphery. The results of a survey among 1400 citizens of Ticino after the vote of 9 February confirm this. In essence, on top of the question of immigration, the vote was influenced by a fearful perception of Ticino as a "double periphery" vis-à-vis both Berne and Lombardy.

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.