Parásitos gastrointestinales de loros habladores silvestres en Chaco, Argentina

Desde su captura hasta el destino final, los loros silvestres experimentan diferentes condiciones durante el transporte, originando así oportunidades de infección y transmisión de enfermedades. Conocer la prevalencia de parásitos en loros habladores silvestres (Amazona aestiva) permitirá un control más eficiente de las parasitosis en aquellos individuos destinados al cautiverio. Además, este trabajo ayudará a determinar qué parásitos son específicos del loro hablador, y cuales son los resultados de infecciones desde otras especies hospedadoras durante el proceso de comercialización. El objetivo de este estudio fue describir los parásitos gastrointestinales de los loros habladores en la región del Impenetrable Chaqueño, en Argentina. Fueron colectadas muestras de heces de 38 pichones y cuatro adultos. También se examinaron cuatro pichones muertos. Un tercio de los nidos inspeccionados (n=21) y un cuarto de los individuos examinados fueron positivos a la presencia de protozoos y helmintos. A nivel individual, Eimeria sp fue el parasito más prevalente (25%), seguido de Isospora sp (5%), Giardia lamblia (5%), Capillaria sp (2%) y Ascaridia sp (2%). Las inspecciones en busca de parásitos en las vísceras de los cuatro pichones hallados muertos por causas naturales, fueron negativas. Como en la mayoría de los estudios con loros silvestres, la prevalencia de parásitos intestinales en el loro hablador fue baja, si se compara con los valores reportados para loros en cautiverio. Debido a que los pichones de este loro son capturados frecuentemente para el tráfico de mascotas, conocer el ensamble de parásitos intestinales y su prevalencia en individuos silvestres, puede ser útil para el tratamiento de pichones destinados al cautiverio.From capture to final destination, wild parrots experience several conditions during transport which enhance/promote chances of infections and transmission of diseases. A better understanding of the prevalence of parasites in wild blue-fronted amazons (Amazona aestiva) will allow a more efficient control of the parasitosis in those individuals destined to captivity. Furthermore, it will be helpful in determining which parasites are specific to the blue-fronted amazons and which are the result of infections from other host species during the commercialization process. The objective of this study was to establish the baseline of gastrointestinal parasites of wild blue-fronted amazons in the Chaco region. We collected fecal samples of 38 nestlings and 4 adults, andexamined four dead nestlings. One-third of examined nests (n=21) and one quarter of the individuals examined were positive for protozoa and helminths. At the individual level, Eimeria sp was the most prevalent (25%), followed by Isospora sp (5%), Giarda lamblia (5%), Capillaria sp (2%) and Ascaridia sp (2%). The tests for parasites in theviscera of the four nestlings found dead from natural causes were negative. As in most wild studies, the prevalence of intestinal parasites in blue-fronted amazons was low, when compared to the parasitic infection levels reported for parrots in captivity. Because the nestlings of this parrot are frequently captured for pet trade, knowledge of theassemblage and prevalence of intestinal parasites of the species in wild individuals can be useful for the treatment of nestlings destined for captivity.Fil: Berkunsky, Igor. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto Multidisciplinario de Ecosistemas y Desarrollo Sustentable; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruggera, Román Alberto. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: López, M. S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Faegre, S. I.. University of Washington; Estados UnidosFil: Aramburu, Rosana Mariel. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Zoología; Argentin

Benchmark study for the application of density functional theory to the prediction of octahedral tilting in perovskites

The results of a systematic study of octahedral tilting in oxo- and fluoroperovskites by density functional theory (DFT) calculations are presented and discussed. Eleven perovskites displaying different structural, magnetic, and metallic properties have been studied by means of nine exchange-correlation functionals, ranging from the basic local density approximation to more advanced hybrid functionals, in order to determine the accuracy of these methods for the prediction of octahedral rotation angles. Octahedral tilting has attracted much attention lately due to the possibility of using them to trigger improper ferroelectricity and new families of multiferroic materials. We show that all DFT methods tend to overestimate the octahedral rotation angles by approximately 20 %, with this quantity being only slightly corrected by hybrids, including, at least, 25% of the Hartree?Fock exchange. We propose a correction to the prediction of these angles based on quantum fluctuations and the anharmonic nature of the energy surface around the minimum but find that it is only important for very small rotation angles appearing in systems like SrTiO3.We acknowledge economic support from the Spanish Ministerio de Ciencia y Tecnolog´ıa under Project No. FIS2012-30996 and the Science Foundation Ireland (SFI) Research Frontiers Programme (Reference No. 10/RFP/MTR2868

Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

Background Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio

Chronic obstructive pulmonary disease subtypes. transitions over time

Background Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time. Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year. Methods Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics. Results Four subtypes were identified. Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity. Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C. Subtype D had higher rates of hospitalization the previous year, and comorbidities. After 1 year, all clusters remained stable. Generally, patients continued in the same subtype but 28% migrated to another cluster. Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to Conclusions Chronic obstructive pulmonary disease clusters remained stable over 1 year. Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes

Lattice models and Landau theory for type II incommensurate crystals

Ground state properties and phonon dispersion curves of a classical linear chain model describing a crystal with an incommensurate phase are studied. This model is the DIFFOUR (discrete frustrated phi4) model with an extra fourth-order term added to it. The incommensurability in these models may arise if there is frustration between nearest-neighbor and next-nearest-neighbor interactions. We discuss the effect of the additional term on the phonon branches and phase diagram of the DIFFOUR model. We find some features not present in the DIFFOUR model such as the renormalization of the nearest-neighbor coupling. Furthermore the ratio between the slopes of the soft phonon mode in the ferroelectric and paraelectric phase can take on values different from -2. Temperature dependences of the parameters in the model are different above and below the paraelectric transition, in contrast with the assumptions made in Landau theory. In the continuum limit this model reduces to the Landau free energy expansion for type II incommensurate crystals and it can be seen as the lowest-order generalization of the simplest Lifshitz-point model. Part of the numerical calculations have been done by an adaption of the Effective Potential Method, orginally used for models with nearest-neighbor interaction, to models with also next-nearest-neighbor interactions.Comment: 33 pages, 7 figures, RevTex, submitted to Phys. Rev.

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Reshaping Silica Particles: Mesoporous Nanodiscs for Bimodal Delivery and Improved Cellular Uptake

The role played by the shape of mesoporous silica nanoparticles has been investigated for intra- and extracellular delivery. Specifically, we have developed the bottom-up synthesis of flat disc-shaped mesoporous silica nanoparticles, the Nanodiscs (NDs). Due to their peculiar shape and large porous system, NDs present a higher cellular uptake than commonly investigated spherical mesoporous nanoparticles. Moreover, NDs are able to efficiently perform exhaustive delivery of their therapeutic cargo when loaded with the anticancer drug Doxorubicin and administered in vitro to cancerous HeLa cells. Thanks to their aspect ratio, NDs can also be readily assembled into well-organized monolayers to be employed in HeLa cells adhesion experiments upon preliminary functionalization with a specific targeting ligand. In these conditions NDs are able to deliver a hydrophobic dye to adhered cells via the highly accessible vertically aligned pores and their flat surface that ensures optimal cell contact. This initial investigation on the performance of NDs in both intra- and extracellular delivery activities suggests the great potential of these particles.This work was financially supported by the European Research Council (ERC) Advanced Grant “MAGIC” (grant N° 247365), the Marie Skłodowska-Curie fellowship (MSCA-IEF) “POP-SILICA” (grant N° 627788) and the SACS Project (grant N° 310651), the Foundation ARC through the project “Thera-HCC” (grant N° IHU201301187), the Région Alsace, and the Département du Bas-Rhin. LDC especially acknowledges AXA Research funds. PHS and SVA acknowledge the Max Planck Society for generous funding

Exclusion of NFAT5 from Mitotic Chromatin Resets Its Nucleo-Cytoplasmic Distribution in Interphase

The transcription factor NFAT5 is a major inducer of osmoprotective genes and is required to maintain the proliferative capacity of cells exposed to hypertonic stress. In response to hypertonicity, NFAT5 translocates to the nucleus, binds to regulatory regions of osmoprotective genes and activates their transcription. Besides stimulus-specific regulatory mechanisms, the activity of transcription factors in cycling cells is also regulated by the passage through mitosis, when most transcriptional processes are downregulated. It was not known whether mitosis could be a point of control for NFAT5.Using confocal microscopy we observed that NFAT5 was excluded from chromatin during mitosis in both isotonic and hypertonic conditions. Analysis of NFAT5 deletions showed that exclusion was mediated by the carboxy-terminal domain (CTD). NFAT5 mutants lacking this domain showed constitutive binding to mitotic chromatin independent of tonicity, which caused them to localize in the nucleus and remain bound to chromatin in the subsequent interphase without hypertonic stimulation. We analyzed the contribution of the CTD, DNA binding, and nuclear import and export signals to the subcellular localization of this factor. Our results indicated that cytoplasmic localization of NFAT5 in isotonic conditions required both the exclusion from mitotic DNA and active nuclear export in interphase. Finally, we identified several regions within the CTD of NFAT5, some of them overlapping with transactivation domains, which were separately capable of causing its exclusion from mitotic chromatin.Our results reveal a multipart mechanism regulating the subcellular localization of NFAT5. The transactivating module of NFAT5 switches its function from an stimulus-specific activator of transcription in interphase to an stimulus-independent repressor of binding to DNA in mitosis. This mechanism, together with export signals acting in interphase, resets the cytoplasmic localization of NFAT5 and prevents its nuclear accumulation and association with DNA in the absence of hypertonic stress

Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice

<p>Abstract</p> <p>Background</p> <p>The transcription factor NFAT5/TonEBP regulates the response of mammalian cells to hypertonicity. However, little is known about the physiopathologic tonicity thresholds that trigger its transcriptional activity in primary cells. Wilkins et al. recently developed a transgenic mouse carrying a luciferase reporter (9xNFAT-Luc) driven by a cluster of NFAT sites, that was activated by calcineurin-dependent NFATc proteins. Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells.</p> <p>Results</p> <p>The 9xNFAT-Luc reporter was activated by hypertonicity in an NFAT5-dependent manner in different types of non-transformed transgenic cells: lymphocytes, macrophages and fibroblasts. Activation of this reporter by the phorbol ester PMA plus ionomycin was independent of NFAT5 and mediated by NFATc proteins. Transcriptional activation of NFAT5 in T lymphocytes was detected at hypertonic conditions of 360–380 mOsm/kg (isotonic conditions being 300 mOsm/kg) and strongly induced at 400 mOsm/kg. Such levels have been recorded in plasma in patients with osmoregulatory disorders and in mice deficient in aquaporins and vasopressin receptor. The hypertonicity threshold required to activate NFAT5 was higher in bone marrow-derived macrophages (430 mOsm/kg) and embryonic fibroblasts (480 mOsm/kg). Activation of the 9xNFAT-Luc reporter by hypertonicity in lymphocytes was insensitive to the ERK inhibitor PD98059, partially inhibited by the PI3-kinase inhibitor wortmannin (0.5 μM) and the PKA inhibitor H89, and substantially downregulated by p38 inhibitors (SB203580 and SB202190) and by inhibition of PI3-kinase-related kinases with 25 μM LY294002. Sensitivity of the reporter to FK506 varied among cell types and was greater in primary T cells than in fibroblasts and macrophages.</p> <p>Conclusion</p> <p>Our results indicate that NFAT5 is a sensitive responder to pathologic increases in extracellular tonicity in T lymphocytes. Activation of NFAT5 by hypertonicity in lymphocytes was mediated by a combination of signaling pathways that differed from those required in other cell types. We propose that the 9xNFAT-Luc transgenic mouse model might be useful to study the physiopathological regulation of both NFAT5 and NFATc factors in primary cells.</p