Unravelling metabolic mechanisms behind chloroplast desiccation tolerance: chlorophyllous fern spore as a new promising unicellular model

Se sustituye el preprint por el postprint el 23-11-2020Fern spores are unicellular structures produced by the sporophyte generation that give rise to the haploid gametophyte. When released from the sporangium, spores are desiccation tolerant (DT) in the royal fern (Osmunda regalis) and contain fully developed chloroplasts. As a consequence this type of spores are called chlorophyllous spores (CS). Upon transfer to germination conditions, CS initiate a process of imbibition that suppress DT in 72h, before the germination starts. In parallel to such change in DT, thylakoids undergo a profound remodelling in composition and function. Firstly, sustained quenching of chlorophyll fluorescence is relaxed, giving rise to photochemically active CS, while lipid composition shifts from that of a resting structure to a metabolically active cell. Basically trigalactolipids decreased in favour of monogalactolipids, with a parallel desaturation of fatty acids. Storage lipids such as triacylglycerol were quickly depleted. These results highlight the importance of the structure of thylakoids lipid as a key to protect membrane integrity during desiccation, together with the saturation of fatty acids and the constitutive chlorophyll quenching to prevent oxidative damage. The CS used here, in which the same cell shifts from DT to sensitive strategy in 72h, reveal its their potential as unicellular models for future studies on DT.This work was funded by (i) the Basque Government (research project UPV/EHU IT-1018-16; and Predoctoral Fellowship to MLP); (ii) the Spanish Ministry of Economy and Competitiveness (MINECO) and the ERDF (FEDER) (research project CTM2014-53902-C2-2-P, and Juan de la Cierva-Incorporation fellowship IJCI-2014-22489 to BFM)

Budgetary impact for the National Health System of Apixaban Prophylaxis of venous thromboembolism in patients undergoing yotal knee or hip replacement

Fundamentos: Debido al elevado coste sanitario del tromboembolismo venoso (TEV) es necesario realizar análisis económicos que determinen la eficiencia de sus diferentes tratamientos farmacológicos. El objetivo del trabajo es estimar el impacto presupuestario para el Sistema Nacional de Salud (SNS) de la prevención del tromboembolismo venoso (TEV) con apixaban en artroplastia total de cadera (ATC) o rodilla (ATR). Métodos: Se consideraron los costes de los diferentes fármacos para la prevención del TEV (apixaban, dabigatrán, enoxaparina, fondaparinux, otras heparinas, rivaroxaban y warfarina) y los de las complicaciones del TEV a corto plazo (90 días) y a 5 años (trombosis venosa profunda, embolismo pulmonar, sangrados y síndrome postrombótico). La eficacia de la prevención se estimó mediante un metaanálisis. Las tasas de TEV y muerte con apixaban fueron inferiores en ATC y ATR a las observadas con enoxaparina (-3,5% y -10,0%, respectivamente) y tuvo menos acontecimientos hemorrágicos (-0,7% y -1,6%, respectivamente). Los datos poblacionales y los costes se obtuvieron de fuentes españolas. Horizonte temporal: 5 años. Todos los costes se descontaron anualmente un 3,5%. Se estimó que a los cinco años de su comercialización el consumo de apixaban supondría el 23% de la prevención del TEV y el de enoxaparina descendería del 60% hasta el 33%. Resultados: La introducción de apixaban para la prevención del TEV produciría un ahorro para el SNS de 547.422 € en un periodo de 5 años. En el caso de considerar sin coste la administración ambulatoria de las heparinas, el ahorro quinquenal para el SNS ascendería a 270.068 €. Conclusiones: La introducción de apixaban podría reducir la tasa de TEV y sangrados en comparación con enoxaparina, reduciéndose el gasto del SNS en la prevención del TEVDue to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of € 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis € 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxisEstudio financiado, sin restricciones, por Bristol-Myers Squibb y Pfize

Trehalose polyphleates, external cell wall lipids in mycobacterium abscessus, are associated with the formation of clumps with cording morphology, which have been associated with virulence

Mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by Mycobacterium tuberculosis. When grown in agar medium, M. abscessus strains generate rough (R) or smooth colonies (S). R morphotypes are more virulent than S morphotypes. In searching for the virulence factors responsible for this difference, R morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. Furthermore, the aggregates released to the extracellular space by damaged macrophages grow, forming unphagocytosable structures that resemble cords. In contrast, bacilli of the S morphotype, which do not form aggregates, do not damage macrophages after phagocytosis and do not form cords. Cording has also been related to the virulence of M. tuberculosis. In this species, the presence of mycolic acids and surface-exposed cell wall lipids has been correlated with the formation of cords. The objective of this work was to study the roles of the surface-exposed cell wall lipids and mycolic acids in the formation of cords in M. abscessus. A comparative study of the pattern and structure of mycolic acids was performed on R (cording) and S (non-cording) morphotypes derived from the same parent strains, and no differences were observed between morphotypes. Furthermore, cords formed by R morphotypes were disrupted with petroleum ether (PE), and the extracted lipids were analyzed by thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry. Substantial amounts of trehalose polyphleates (TPP) were recovered as major lipids from PE extracts, and images obtained by transmission electron microscopy suggested that these lipids are localized to the external surfaces of cords and R bacilli. The structure of M. abscessus TPP was revealed to be similar to those previously described in Mycobacterium smegmatis. Although the exact role of TPP is unknown, our results demonstrated that TPP are not toxic by themselves and have a function in the formation of clumps and cords in M. abscessus, thus playing an important role in the pathogenesis of this species

The veil of flor’s structure, composition and interactions in biological ageing wines

Biological ageing occurs after fermentation of the grape must and it is due to the appearance of a biofilm on the surface of the wine called "veil of flor". Yeast involved in veil formation are mainly Saccharomyces cerevisiae and they have traditionally been divided into four races according to their ability to metabolize different sugars. The growth of flor yeasts depends on different factors, such as the aerobic assimilation of the wine ethanol, since the medium is deficient in both sugars and nitrogen. Actually, flor yeast metabolism is different from wine S. cerevisiae yeast, but it hasn't been analysed yet. Thus, the aim of this work is to study the diversity of flor yeast strains and to analyse the composition and the structure of the veil of flor in Jerez-Xeres-Sherry D.O. The results of this work revealed 14 different genotypes of S. cerevisiae strains using multiplex-microsatellite PCR and these strains showed 8 different biochemical profiles using a similar procedure than traditionally. In addition, mannose and glucose were found in veil of flor complex using UHPLC-MS

Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats.Fil: Fernandez, Marina Olga. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bianchi, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Tyramine biosynthesis is transcriptionally induced at low pH and improves the fitness of Enterococcus faecalis in acidic environments

© 2014, Springer-Verlag Berlin Heidelberg. Enterococcus faecalis is a commensal bacterium of the human gut that requires the ability to pass through the stomach and therefore cope with low pH. E. faecalis has also been identified as one of the major tyramine producers in fermented food products, where they also encounter acidic environments. In the present work, we have constructed a non-tyramine-producing mutant to study the role of the tyramine biosynthetic pathway, which converts tyrosine to tyramine via amino acid decarboxylation. Wild-type strain showed higher survival in a system that mimics gastrointestinal stress, indicating that the tyramine biosynthetic pathway has a role in acid resistance. Transcriptional analyses of the E. faecalis V583 tyrosine decarboxylase cluster showed that an acidic pH, together with substrate availability, induces its expression and therefore the production of tyramine. The protective role of the tyramine pathway under acidic conditions appears to be exerted through the maintenance of the cytosolic pH. Tyramine production should be considered important in the adaptability of E. faecalis to acidic environments, such as fermented dairy foods, and to survive passage through the human gastrointestinal tract.This work was funded by the Ministry of Economy and Competitiveness, Spain (AGL2013-45431-R) and the Spanish National Research Council (CSIC201270E144). M.P. is beneficiary of an FPU fellowship from the Spanish Ministry of Education.Peer Reviewe

Transmission dynamics of an iridescent virus in an experimental mosquito population: the role of host density.

1. The transmission of insect pathogens cannot be adequately described by direct linear functions of host and pathogen density due to heterogeneity generated from behavioural or physiological traits, or from the spatial distribution of pathogen particles. Invertebrate iridescent viruses (IIVs) can cause patent and lethal infection or a covert sub-lethal infection in insects. Aedes aegypti larvae were exposed to suspensions of IIV type 6 at two densities. High larval density increased the prevalence of aggression resulting in potentially fatal wounding. 2. The overall prevalence of infection (patent + covert) was positively influenced by host density and increased with exposure time in both densities. The survival time of patently infected insects was extended by ≈ 5 days compared with non-infected insects. 3. Maximum likelihood models based on the binomial distribution were fitted to empirical results. A model incorporating heterogeneity in host susceptibility by inclusion of a pathogen-free refuge was a significantly better fit to data than an all-susceptible model, indicating that transmission is non-linear. The transmission coefficient (υ) did not differ with host density whereas the faction of the population that occupied the pathogen-free refuge (ΠR) was significantly reduced at high host density compared with the low density treatment. 4. The transmission of free-living infective stages of an IIV in Ae. aegypti larvae is non-linear, probably because of density-related changes in the frequency of aggressive encounters between hosts. This alters host susceptibility to infection and effectively reduces the proportion of hosts that occupy the pathogen-free refuge

Serum periostin levels in fibrous dysplasia: Its usefulness as disease biomarker. An exploratory study

Objective: Fibrous dysplasia (FD) is a rare, non-hereditary bone disease caused by a somatic mutation of GNAS gene. Periostin (Postn) is a new marker, linked to bone repair processes. We aimed to assess Postn sensitivity as disease activity marker of FD.Methods: An exploratory case-control study was led, with 15 FD patients, paired by age and gender with healthy subjects (controls). Postn serum levels were gauged in FD patients and controls, also according to clinical manifestation. In the same assay, with serum samples stored at -80°C, Postn was measured by the ELISA method (Sigma Aldrich; St. Louis, USA), [coefficient of variation (%CV) intra-assay <10% and interassay<12%]. Statistical analysis: an R Core Team 2018 processor wasused (https://www.R-project.org). A nonparametric test (MannWhitney)was used to compared Postn serum levels between the groups. ROC curves were used to find optimal cut-off points andanalyze Postn sensitivity (predictive value).Results: 15 FD patients (polyostotic 40%, monostotic 33% and McCune-Albright syndrome 27%), with an average age (X±DS) of 44.3±10 y. In our FD patient cohort, no statistically significantdifferences were observed between Postn and control group (FD: 51.1±10 ng/ml vs. control: 44.2±15 ng/ml; p=0.15) nor by FD clinical form (polyostotic: 51.8±9.1 ng/ml vs. monostotic:49.6±13 ng/ml; p=0.66). Figure 1 shows the ROC curve obtained and optimal cut-off points.Conclusion: Postn serum levels did not show statistically significant differences compared to control group or by clinical manifestation, showing low sensitivity as disease activity markerof FD.Funding: UBACYT 2018 (#0113).Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: González, Diana. Mautalen Salud e Investigación ; ArgentinaFil: Tetzlaff, T. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gianotti, G. R.. Mautalen Salud e Investigación ; ArgentinaFil: Fernández, F. C.. Mautalen Salud e Investigación ; ArgentinaFil: Gómez Glorioso, G. G. D.. Mautalen Salud e Investigación ; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaWorld Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesBarcelonaEspañaInternational Osteoporosis FoundationEuropean Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease

SrMnO3 thermochromic behavior governed by size-dependent structural distortions

The influence of particle size in both the structure and thermochromic behavior of 4H-SrMnO related perovskite is described. Microsized SrMnO suffers a structural transition from hexagonal (P6/mmc) to orthorhombic (C222) symmetry at temperature close to 340 K. The orthorhombic distortion is due to the tilting of the corner-sharing MnO units building the 4H structural type. When temperature decreases, the distortion becomes sharper reaching its maximal degree at ∼125 K. These structural changes promote the modification of the electronic structure of orthorhombic SrMnO phase originating the observed color change. nano-SrMnO adopts the ideal 4H hexagonal structure at room temperature, the orthorhombic distortion being only detected at temperature below 170 K. A decrease in the orthorhombic distortion degree, compared to that observed in the microsample, may be the reason why a color change is not observed at low temperature (77 K)

Mycobacteria clumping increase their capacity to damage macrophages

The rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. This idea is consistent with the fact that Mycobacterium tuberculosis presents a stable rough morphotype. Unlike smooth morphotypes, the bacilli of rough morphotypes grow close together, leaving no spaces among them and forming large aggregates (clumps). Currently, the initial interaction of macrophages with clumps remains unclear. Thus, we infected J774 macrophages with bacterial suspensions of rough morphotypes of M. abscessus containing clumps and suspensions of smooth morphotypes, primarily containing isolated bacilli. Using confocal laser scanning microscopy and electron microscopy, we observed clumps of at least five rough-morphotype bacilli inside the phagocytic vesicles of macrophages at 3 h post-infection. These clumps grew within the phagocytic vesicles, killing 100% of the macrophages at 72 h post-infection, whereas the proliferation of macrophages infected with smooth morphotypes remained unaltered at 96 h post-infection. Thus, macrophages phagocytose large clumps, exceeding the bactericidal capacities of these cells. Furthermore, proinflammatory cytokines and granuloma-like structures were only produced by macrophages infected with rough morphotypes. Thus, the present study provides a foundation for further studies that consider mycobacterial clumps as virulence factors