Non-minimally coupled tachyon field with Noether symmetry under the Palatini approach

A model for a homogeneous, isotropic, flat Universe composed by dark energy and matter is investigated. Dark energy is considered to behave as a tachyon field, which is non-minimally coupled to gravity. The connection is treated as metric independent when varying the action, providing an extra term to the Lagrangian density. The self-interaction potential and coupling are naturally found by imposing a Noether symmetry to the system. We analyze the evolution of the density parameters and we compare the results obtained for the deceleration parameter, luminosity distance and Hubble parameter with those found in literature from observational data.Comment: 6 pages, 4 figures to be published in the AIP Conference Proceeding

Campos taquiônicos não-minimamente acoplados, abordagem de Palatini e simetrias de Noether

Orientador: Prof. Dr. Gilberto Medeiros KremerDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Exatas, Programa de Pós-Graduação em Física. Defesa: Curitiba, 25/07/2014Inclui referênciasResumo: Neste trabalho, analisamos três modelos cosmológicos com uma ação primária em comum. A energia-escura e interpretada como um campo taquiônico não-minimamente acoplado a gravidade. Em todos os casos, consideramos um Universo composto por energia- escura e matéria, e em um deles, admitimos também a radiação. A conexão afim não e previamente assumida como compatível com a métrica, mas encontrada independentemente através da variação da ação com seu respeito: abordagem de Palatini. As funções que definem o acoplamento não-mínimo e o potencial de auto-interação são obtidas por um gerador de simetria, que restringe a ação a uma que possui determinadas invariâncias sob transformações pontuais. Os resultados obtidos são confrontados com recentes dados observacionais.Abstract: In this work, three models described by a common general action are analyzed. Dark energy is interpreted as a tachyon field non-minimally coupled to gravity. We consider a Universe composed by matter and dark energy in all of the three cases, plus a radiation field in one of them. The affine connection is taken to be metric independent and we find it by the Palatini approach. The functions that define the non-minimally coupling and the self-interaction potential are not set by an ad-hoc manner, but by imposing the system to present any Noether symmetry instead. The systems’ behavior and the results obtained from them are then compared to recent observational data

Chemotherapeutic Candidate Inducing Immunological Death of Human Tumor Cell Lines

The immunological death induction by EY-6 on the human tumor cell lines was screened. Human colon carcinoma (HCT15, HCT116), gastric carcinoma (MKN74, SNU668), and myeloma (KMS20, KMS26, KMS34) cells were died by EY-6 treatment with dose-dependent manner. CRT expression, a typical marker for the immunological death, was increased on the EY-6-treated colorectal and gastric cancer cells. Interestingly, the effects on the myeloma cell lines were complicated showing cell line dependent differential modulation. Cytokine secretion from the EY-6 treated tumor cells were dose and cell-dependent. IFN-γ and IL-12 secretion was increased in the treated cells (200% to over 1000% of non-treated control), except HCT116, SNU668 and KMS26 cells which their secretion was declined by EY-6. Data suggest the potential of EY-6 as a new type of immuno-chemotherapeutics inducing tumor-specific cell death. Further studies are planned to confirm the efficacy of EY-6 including in vivo study

Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line

This article is made available through the Brunel Open Access Publishing Fund. Copyright: © 2013 Mahajan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and timedependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2) showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SPD in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host’s immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.Department of Biotechnology, Indi

Differential expression of collectins in human placenta and role in inflammation during spontaneous Labor.

© 2014 Yadav et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Collectins, collagen-containing Ca2+ dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (p<0.05). In addition, the MMP-9-cleaved form of SP-D (25 kDa) was significantly higher in the placentae of 'SLv' group compared to the 'NLc' group (p = 0.002). Labor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (p<0.05) in a dose dependent manner in the placental explants treated with nSP-D and rhSP-D. In conclusion, the study emphasizes that SP-A and SP-D proteins associate with the spontaneous labor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.Funding provided by BT/PR15227/BRB/10/906/2011) Department of Biotechnology (DBT), Government of India http://dbtindia.nic.in/index.asp (TM) and Indian Council of Medical Research (ICMR) Junior Research Fellowship (JRF)/Senior Research Fellowship (SRF), Government of India, www.icmr.nic.in (AKY)

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

A role for calreticulin in the pathogenesis of rheumatoid arthritis

Calreticulin (CRT) plays a role in the clearance of dying cells and has been implicated in autoimmunity. Recent evidence indicates that cell surface CRT (csCRT) acts as a signal transducing receptor for the rheumatoid arthritis (RA) shared epitope (SE). The SE binding site on CRT has been mapped to amino acid residues 217–223 in the P-domain. Upon interaction with dendritic cells (DCs), the SE activates potent immune regulatory events. In CD8α + DCs, which express higher abundance of csCRT, the SE inhibits the tolerogenic enzyme indoleamine 2,3 dioxygenase with resultant inhibition of regulatory T (Treg) cell differentiation. In CD8α − DCs, the SE ligand increases secretion of IL-6 and IL-23 and facilitates generation of Th17 cells, a T cell subset known to play a role in autoimmunity. On the basis of these recent findings, we discuss the possibility that the csCRT may play a pathogenic role in RA by transducing SE-activated Th17-polarizing signals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79357/1/j.1749-6632.2010.05745.x.pd

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)