Unveiling the Role of the Integrated Endoplasmic Reticulum Stress Response in Leishmania Infection - Future Perspectives.

The integrated endoplasmic reticulum stress response (IERSR) is an evolutionarily conserved adaptive mechanism that ensures endoplasmic reticulum (ER) homeostasis and cellular survival in the presence of stress including nutrient deprivation, hypoxia, and imbalance of Ca(+) homeostasis, toxins, and microbial infection. Three transmembrane proteins regulate integrated signaling pathways that comprise the IERSR, namely, IRE-1 that activates XBP-1, the pancreatic ER kinase (PERK) that phosphorylates the eukaryotic translation initiation factor 2 and transcription factor 6 (ATF6). The roles of IRE-1, PERK, and ATF4 in viral and some bacterial infections are well characterized. The role of IERSR in infections by intracellular parasites is still poorly understood, although one could anticipate that IERSR may play an important role on the host's cell response. Recently, our group reported the important aspects of XBP-1 activation in Leishmania amazonensis infection. It is, however, necessary to address the relevance of the other IERSR branches, together with the possible role of IERSR in infections by other Leishmania species, and furthermore, to pursue the possible implications in the pathogenesis and control of parasite replication in macrophages

Effects of landscape metrics and land-use variables on macroinvertebrate communities and habitat characteristics

ABSTRACT: The growing number of studies establishing links between stream biota, environmental factors and river classification has contributed to a better understanding of fluvial ecosystem function. Environmental factors influencing river systems are distributed over hierarchically organised spatial scales. We used a nested hierarchical sampling design across four catchments to assess how benthic macroinvertebrate community composition and lower spatial scale habitat descriptors were shaped by landscape and land-use patterns. We found that benthic macroinvertebrate community structure and composition varied significantly from catchment to habitat level. We assessed and identified fractal metrics of landscape descriptors capable of explaining compositional and functional change in the benthic faunal indicators and compared them with the traditional variables describing land use and reach level habitat descriptors within a 1 km radius of each sampling site. We found that fractal landscape metrics were the best predictor variables for benthic macroinvertebrate community composition, function, instream habitat and river corridor characteristics

Kinin B2 receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice

BACKGROUND: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)35-55-induced EAE in mice. METHODS: In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT) and kinin B2 receptor knockout (B2-/-) mice subjected to MOG35-55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B2-/- and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA. RESULTS: Clinical parameters of disease were reduced in B2-/- mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B2-/- mice when compared to WT. CONCLUSION: Our results suggest that B2 receptors have two major effects in the control of EAE severity: (i) B2 regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B2 modulates leukocyte recruitment and inflammatory lesions in the CNS

Morphological and microstructural characterization of laser-glazedplasma-sprayed thermal barrier coatings

Laser glazing has been revealing a high potential for the improvement of plasma-sprayed (PS) thermal barrier coatings (TBCs) by reducing surface roughness, eliminating open porosity on the surface and generating a controlled segmented crack network, although the relationship of the processing parameters with the resultant properties has not yet been completely established. In this investigation, TBCs consisting of atmospheric plasma-sprayed (APS) ZrO2–8wt.%Y2O3 were subjected to a CO2 continuous wave laser-glazing process in order to seal its surface porosity, generating an external dense layer. For that purpose, different amounts of radiation resulting from different scanning speeds were applied to the specimens as well as different track overlapping. Results have shown a significant decrease of the surface roughness after the laser treatment. All specimens presented a fully dense and porous free external layer with a polyfaceted columnar microstructure highly adherent to the plasma-sprayed coating. Controlled surface crack networks, extremely dependent on the laser scanning speed and track overlapping, were achieved for each set of processing parameters. The cracks were found to have a tendency to be oriented in two perpendicular directions, one in the direction of the laser-beam travel direction, the other perpendicular to it. Moreover, the cracks parallel to the beam travel direction are found to be on the overlapping zone, coinciding with the edge of the subsequent track. The cracks are perpendicular to the surface along the densified layer and tend to branch and deviate from the vertical direction below it, within the porous PS coating. XRD results revealed mainly tV nontransformable tetragonal zirconia with a small percentage of residual monoclinic zirconia for the as-sprayed coating. All glazed coatings presented only tV nontransformable tetragonal zirconia with some variations on preferable crystal orientation. Grain sizes varied from 26 to 52 nm, increasing with an increase of laserirradiated energy; microstrain behaved inversely.Fundação para a Ciência e a Tecnologia (FCT) - Project POCTI/CTM/44590/2002.União Europeia (UE). Fundo Europeu de Desenvolvimento Regional (FEDER)

Beneficial effects of the activation of the Angiotensin-(1-7) MAS receptor in a murine model of adriamycin-induced nephropathy

Angiotensin-(1-7) [Ang-(1-7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-{beta}. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas(+/+)) and Mas knockout (Mas (-/-)) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas(+/+) , but not in Mas (-/-) mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1-7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies

Transcriptional activity, chromosomal distribution and expression effects of transposable elements in Coffea genomes

Plant genomes are massively invaded by transposable elements (TEs), many of which are located near host genes and can thus impact gene expression. In flowering plants, TE expression can be activated (de-repressed) under certain stressful conditions, both biotic and abiotic, as well as by genome stress caused by hybridization. In this study, we examined the effects of these stress agents on TE expression in two diploid species of coffee, Coffea canephora and C. eugenioides, and their allotetraploid hybrid C. arabica. We also explored the relationship of TE repression mechanisms to host gene regulation via the effects of exonized TE sequences. Similar to what has been seen for other plants, overall TE expression levels are low in Coffea plant cultivars, consistent with the existence of effective TE repression mechanisms. TE expression patterns are highly dynamic across the species and conditions assayed here are unrelated to their classification at the level of TE class or family. In contrast to previous results, cell culture conditions per se do not lead to the de-repression of TE expression in C. arabica. Results obtained here indicate that differing plant drought stress levels relate strongly to TE repression mechanisms. TEs tend to be expressed at significantly higher levels in non-irrigated samples for the drought tolerant cultivars but in drought sensitive cultivars the opposite pattern was shown with irrigated samples showing significantly higher TE expression. Thus, TE genome repression mechanisms may be finely tuned to the ideal growth and/or regulatory conditions of the specific plant cultivars in which they are active. Analysis of TE expression levels in cell culture conditions underscored the importance of nonsense-mediated mRNA decay (NMD) pathways in the repression of Coffea TEs. These same NMD mechanisms can also regulate plant host gene expression via the repression of genes that bear exonized TE sequences. (Résumé d'auteur

Pectin as a Biomaterial in Regenerative Endodontics—Assessing Biocompatibility and Antibacterial Efficacy against Common Endodontic Pathogens: An In Vitro Study

Regenerative endodontics (REP) is a new clinical modality aiming to regenerate damaged soft and hard dental tissues, allowing for root completion in young adults’ teeth. Effective disinfection is crucial for REP success, but commonly used antimicrobials often harm the niche dental pulp stem cells (DPSCs). To our knowledge, this is the first study to explore the biocompatibility and antimicrobial potential of pectin as a potential natural intracanal medicament for REPs. Low methoxyl commercial citrus pectin (LM) (pectin CU701, Herbstreith&Fox.de) was used in all experiments. The pectin’s antibacterial activity against single species biofilms (E. faecalis and F. nucleatum) was assessed using growth curves. The pectin’s antimicrobial effect against mature dual-species biofilm was also evaluated using confocal laser scanning microscopy (CLSM) after 30 min and 7 days of treatment. The DPSC biocompatibility with 2% and 4% w/v of the pectin coatings was evaluated using live/dead staining, LDH, and WST-1 assays. Pectin showed a concentration-dependent inhibitory effect against single-species biofilms (E. faecalis and F. nucleatum) but failed to disrupt dual-species biofilm. Pectin at 2% w/v concentration proved to be biocompatible with the HDPSCs. However, 4% w/v pectin reduced both the viability and proliferation of the DPSCs. Low concentration (2% w/v) pectin was biocompatible with the DPSCs and showed an antimicrobial effect against single-species biofilms. This suggests the potential for using pectin as an injectable hydrogel for clinical applications in regenerative endodontics

Gravitational field around a time-like current-carrying screwed cosmic string in scalar-tensor theories

In this paper we obtain the space-time generated by a time-like current-carrying superconducting screwed cosmic string(TCSCS). This gravitational field is obtained in a modified scalar-tensor theory in the sense that torsion is taken into account. We show that this solution is comptible with a torsion field generated by the scalar field $\phi$. The analysis of gravitational effects of a TCSCS shows up that the torsion effects that appear in the physical frame of Jordan-Fierz can be described in a geometric form given by contorsion term plus a symmetric part which contains the scalar gradient. As an important application of this solution, we consider the linear perturbation method developed by Zel'dovich, investigate the accretion of cold dark matter due to the formation of wakes when a TCSCS moves with speed $v$ and discuss the role played by torsion. Our results are compared with those obtained for cosmic strings in the framework of scalar-tensor theories without taking torsion into account.Comment: 21 pages, no figures, Revised Version, presented at the "XXIV- Encontro Nacional de Fisica de Particulas e Campos ", Caxambu, MG, Brazil, to appear in Phys. Rev.