A collimated, ionized bipolar structure and a high density torus in the young planetary nebula IRAS 17347-3139

We present observations of continuum (lambda = 0.7, 1.3, 3.6 and 18 cm) and OH maser (lambda = 18 cm) emission toward the young planetary nebula IRAS 17347-3139, which is one of the three planetary nebulae that are known to harbor water maser emission. From the continuum observations we show that the ionized shell of IRAS 17347-3139 consists of two main structures: one extended (size ~1". 5) with bipolar morphology along PA=-30 degrees, elongated in the same direction as the lobes observed in the near-infrared images, and a central compact structure (size ~0". 25) elongated in the direction perpendicular to the bipolar axis, coinciding with the equatorial dark lane observed in the near-infrared images. Our image at 1.3 cm suggests the presence of dense walls in the ionized bipolar lobes. We estimate for the central compact structure a value of the electron density at least ~5 times higher than in the lobes. A high resolution image of this structure at 0.7 cm shows two peaks separated by about 0". 13 (corresponding to 100-780 AU, using a distance range of 0.8-6 kpc). This emission is interpreted as originating in an ionized equatorial torus-like structure, from whose edges the water maser emission might be arising. We have detected weak OH 1612 MHz maser emission at VLSR ~ -70 km/s associated with IRAS 17347-3139. We derive a 3 sigma upper limit of < 35% for the percentage of circularly polarized emission. Within our primary beam, we detected additional OH 1612 MHz maser emission in the LSR velocity ranges -5 to -24 and -90 to -123 km/s, associated with the sources 2MASS J17380406-3138387 and OH 356.65-0.15, respectively.Comment: 26 pages, 8 figures. Accepted for publication in Ap

Spectral index of the H2O-maser emitting planetary nebula IRAS 17347-3139

We present radio continuum observations of the planetary nebula (PN) IRAS 17347-3139 (one of the only two known to harbour water maser emission), made to derive its spectral index and the turnover frequency of the emission. The spectrum of the source rises in the whole frequency range sampled, from 2.4 to 24.9 GHz, although the spectral index seems to decrease at the highest frequencies (0.79+-0.04 between 4.3 and 8.9 GHz, and 0.64+-0.06 between 16.1 and 24.9 GHz). This suggests a turnover frequency around 20 GHz (which is unusual among PNe, whose radio emission usually becomes optically thin at frequencies < 10 GHz), and a relatively high emission measure (1.5 x 10^9 cm^{-6} pc). The radio continuum emission has increased by a factor of ~1.26 at 8.4 GHz in 13 years, which can be explained as expansion of the ionized region by a factor of ~1.12 in radius with a dynamical age of ~120 yr and at an expansion velocity of ~5-40 km/s. These radio continuum characteristics, together with the presence of water maser emission and a strong optical extinction suggest that IRAS 17347-3139 is one of the youngest PNe known, with a relatively massive progenitor star.Comment: Five pages, 2 figures, accepted by MNRA

Therapeutic Strategies of Secretome of Mesenchymal Stem Cell

Great progress has been made in the therapeutic strategies of multiple diseases that lack curative treatments with the transplantation of mesenchymal stem cells (MSC), such as in onco-hematological diseases, myocardial infarction (MI), cerebrovascular diseases, degenerative diseases of the nervous system (multiple sclerosis, Alzheimer’s disease), and diseases of the immune system, among others. Stem cells (SC) participate in the biological processes of tissue regeneration and repair through cell replication. Recently, the beneficial therapeutic effects of SCs that are generated by the release of proteins with paracrine actions and not by cell differentiation are more well known, and 80% of the therapeutic effect of SC is attributed to paracrine actions. The MSCs release large amounts of proteins and growth factors (GF), nucleic acids, proteasomes, exosomes, and microRNA, and membrane vesicles known as the secretome are released into the extracellular space, regulating multiple biological processes. Currently, the therapeutic strategies in tissue engineering (TE) and regenerative medicine (RM) are focused on the management of products derived from cells that act, both locally and remotely, in the affected tissue or organ, achieving regenerative actions. The application of new knowledge of the secretome initiates a change in the paradigm of regenerative therapy by knowing more about and using cell products derived from cells as a “factory” for biological drugs

Stimulation of TLR3 Triggers Release of Lysosomal ATP in Astrocytes and Epithelial Cells That Requires TRPML1 Channels

Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and non-targeting scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1-/- cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways. © 2018 The Author(s)

Production and purification of immunologically active core protein p24 from HIV-1 fused to ricin toxin B subunit in E. coli

<p>Abstract</p> <p>Background</p> <p>Gag protein from HIV-1 is a polyprotein of 55 kDa, which, during viral maturation, is cleaved to release matrix p17, core p24 and nucleocapsid proteins. The p24 antigen contains epitopes that prime helper CD4 T-cells, which have been demonstrated to be protective and it can elicit lymphocyte proliferation. Thus, p24 is likely to be an integral part of any multicomponent HIV vaccine. The availability of an optimal adjuvant and carrier to enhance antiviral responses may accelerate the development of a vaccine candidate against HIV. The aim of this study was to investigate the adjuvant-carrier properties of the B ricin subunit (RTB) when fused to p24.</p> <p>Results</p> <p>A fusion between ricin toxin B subunit and p24 HIV (RTB/p24) was expressed in <it>E. coli</it>. Affinity chromatography was used for purification of p24 alone and RTB/p24 from cytosolic fractions. Biological activity of RTB/p24 was determined by ELISA and affinity chromatography using the artificial receptor glycoprotein asialofetuin. Both assays have demonstrated that RTB/p24 is able to interact with complex sugars, suggesting that the chimeric protein retains lectin activity. Also, RTB/p24 was demonstrated to be immunologically active in mice. Two weeks after intraperitoneal inoculation with RTB/p24 without an adjuvant, a strong anti-p24 immune response was detected. The levels of the antibodies were comparable to those found in mice immunized with p24 alone in the presence of Freund adjuvant. RTB/p24 inoculated intranasally in mice, also elicited significant immune responses to p24, although the response was not as strong as that obtained in mice immunized with p24 in the presence of the mucosal adjuvant cholera toxin.</p> <p>Conclusion</p> <p>In this work, we report the expression in <it>E. coli </it>of HIV-1 p24 fused to the subunit B of ricin toxin. The high levels of antibodies obtained after intranasal and intraperitoneal immunization of mice demonstrate the adjuvant-carrier properties of RTB when conjugated to an HIV structural protein. This is the first report in which a eukaryotic toxin produced in <it>E. coli </it>is employed as an adjuvant to elicit immune responses to p24 HIV core antigen.</p

A Boron Dipyrromethene (BODIPY)-Based Cu-II-Bipyridine Complex for Highly Selective NO Detection

[EN] A BODIPY-containing Cu-II-bipyridine complex for the simple selective fluorogenic detection of NO in air and in live cells is reported. The detection mechanism is based on NO-promoted Cu-II to Cu-I reduction, followed by demetallation of the complex, which results in the clearly enhanced emission of the boron dipyrromethene (BODIPY) unit.The authors thank the DGICYT and European FEDER funds (MAT2012-38429-C04-01 and MAT2012-38429-C04-02) and the Generalitat Valenciana (PROMETEOII/2014/047) for support. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed.Juárez, LA.; Barba Bon, A.; Costero Nieto, AM.; Martínez Mañez, R.; Sancenón Galarza, F.; Parra Álvarez, M.; Gaviña Costero, P.... (2015). A Boron Dipyrromethene (BODIPY)-Based Cu-II-Bipyridine Complex for Highly Selective NO Detection. CHEMISTRY-A EUROPEAN JOURNAL. 21(44):15486-15490. https://doi.org/10.1002/chem.201502191S1548615490214

Anisakis pegreffii impacts differentiation and function of human dendritic cells

Human dendritic cells (DCs) show remarkably phenotypic changes when matured in presence of helminth-derived products. These modifications frequently elicited a polarization towards Th2 cells and regulatory T cells thus contributing to immunological tolerance against these pathogens. In this study, the interaction between DCs and larvae of the zoonotic anisakid nematode Anisakis pegreffii was investigated. A. pegreffii larvae were collected from fish hosts and monocyte derived DCs were co-cultured in the presence of the live larvae (L) or its crude extracts (CE). In both experimental conditions A. pegreffii impacted DC viability, hampered DC maturation by reducing the expression of molecules involved in antigen presentation and migration (i.e. HLA-DR, CD86, CD83 and CCR7), increased the phagosomal ROS levels and modulated the phosphorylation of ERK1,2 pathway. These biological changes were accompanied by the impairment of DCs to activate a T cell mediated IFN. Interestingly, live larva appeared to differently modulate DC secretion of cytokines and chemokines as compared to CE. These results demonstrate for the first time the immunomodulatory role of A. pegreffi on DCs biology and functions. In addition, they suggest a dynamic contribution of DCs to the induction and maintenance of the inflammatory response against A. pegreffi

Stimulation of TLR3 Triggers Release of Lysosomal ATP in Astrocytes and Epithelial cells that Requires TRPML1 Channels

Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and “non-targeting” scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1−/− cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways

Stimulation of TLR3 Triggers Release of Lysosomal ATP in Astrocytes and Epithelial Cells that Requires TRPML1 Channels

Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and non-targeting scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1-/- cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways. © 2018 The Author(s)