Palma, Carla; Schiavoni, Giovanna; Abalsamo, Laura; Mattei, Fabrizio; Piccaro, Giovanni; Sanchez, Massimo; Fernandez, Carmen; Singh, Mahavir; Gabriele, Lucia
2013-09-01
The immunological mechanisms that modulate protection during Mycobacterium tuberculosis (Mtb) infection or vaccination are not fully understood. Secretion of IFN-γ and, to a lesser extent, of IL-17 by CD4(+) T cells plays a major role both in protection and immunopathology. Few Mtb Ags interacting with DCs affect priming, activation, and regulation of Ag-unrelated CD4(+) T-cell responses. Here we demonstrate that PstS1, a 38 kDa-lipoprotein of Mtb, promotes Ag-independent activation of memory T lymphocytes specific for Ag85B or Ag85A, two immunodominant protective Ags of Mtb. PstS1 expands CD4(+) and CD8(+) memory T cells, amplifies secretion of IFN-γ and IL-22 and induces IL-17 production by effector memory cells in an Ag-unrelated manner in vitro and in vivo. These effects were mediated through the stimulation of DCs, particularly of the CD8α(-) subtype, which respond to PstS1 by undergoing phenotypic maturation and by secreting IL-6, IL-1β and, to a lower extent, IL-23. IL-6 secretion by PstS1-stimulated DCs was required for IFN-γ, and to a lesser extent for IL-22 responses by Ag85B-specific memory T cells. These results may open new perspectives for immunotherapeutic strategies to control Th1/Th17 immune responses in Mtb infections and in vaccinations against tuberculosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Andrade, María Luisa; Vega, Flora A.
2015-01-01
Sorption and desorption experiments were performed by the batch method on the B horizons of five natural soils: Umbric Cambisol, Endoleptic Luvisol, Mollic Umbrisol, Dystric Umbrisol, and Dystric Fluvisol. Individual and competitive sorption and desorption capacity and hysteresis were determined. The results showed that Pb2+ was sorbed and retained in a greater quantity than Cd2+ and that the hysteresis of the first was greater than that of the second. The most influential characteristics of the sorption and retention of Pb2+ were pH, ECEC, Fe and Mn oxides and clay contents. For Cd2+ they were mainly pH and, to a lesser extent, Mn oxides and clay content. The combined use of TOF-SIMS, FE-SEM/EDS and sorption and desorption analyses was suitable for achieving a better understanding of the interaction between soil components and the two heavy metals. They show the preferential association of Pb2+ with vermiculite, chlorite, Fe and Mn oxides, and of Cd2+ with the same components, although to a much lesser extent and intensity. This was due to the latter’s higher mobility as it competed unfavourably with the Pb2+ sorption sites. TOF-SIMS and FE-SEM/EDS techniques confirmed the results of the sorption experiments, and also provided valuable information on whether the soil components (individually or in association) retain Cd2+ and / or Pb2+; this could help to propose effective measures for the remediation of contaminated soils. PMID:25893518
CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception
Sciaranghella, Gaia; Wang, Cuiwei; Hu, Haihong; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z.; Greenblatt, Ruth M.; Cohen, Mardge; Golub, Elizabeth T.; Watts, D. Heather; Alter, Galit; Young, Mary A.; Tsibris, Athe M. N.
2015-01-01
Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4+ and CD8+ T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression. PMID:25895986
Carnec, Xavier; Meertens, Laurent; Dejarnac, Ophélie; Perera-Lecoin, Manuel; Hafirassou, Mohamed Lamine; Kitaura, Jiro; Ramdasi, Rasika; Schwartz, Olivier; Amara, Ali
2016-01-01
Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection. Dengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans and is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM and TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells and mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a-dependent DENV infection relies on the direct recognition of phosphatidylethanolamine and to a lesser extent PtdSer associated with viral particles. This study provides novel insights into the mechanisms that mediate DENV entry and reinforce the concept that DENV uses an apoptotic mimicry strategy for viral entry. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Pillatzki, Angela E.; Neiger, Regg D.; Chipps, Steven R.; Higgins, Kenneth F.; Thiex, Nancy; Afton, Alan D.
2011-01-01
High concentrations of some hepatic elements might be contributing to the decline of the continental lesser scaup (Aythya affinis) population. We evaluated hepatic element concentrations of male and female lesser scaup collected from the upper Midwest (Iowa, Minnesota, North Dakota, and South Dakota) during the 2003 and 2004 spring migrations. We measured concentrations of 24 elements in livers of 117 lesser scaup. We found that only selenium concentrations were at levels (>3.0 μg/g wet weight [ww)]) proposed to adversely affect reproduction. Approximately 49% of females (n = 61) had individual hepatic concentrations >3.0 μg/g ww selenium (Se). Our observed hepatic concentration of Se was similar to that reported in lesser scaup collected from the mid-continental United States but less than Se concentrations reported from the Great Lakes region. We found that the liver cadmium (Cd) concentration for males was significantly higher than that for females. Gender differences in hepatic Cd concentrations have not been previously reported for lesser scaup, but Cd is known to have negative impacts on male reproduction. Our results indicate that lesser scaup migrating through the upper Midwest in spring have elevated Se levels and that males carry a significantly greater Cd burden than females. Moreover, elemental concentrations might be high enough to affect reproduction in both male and female lesser scaup, but controlled laboratory studies are needed to adequately assess the effects of Se and Cd on lesser scaup reproduction.
Pillatzki, A.E.; Neiger, R.D.; Chipps, S.R.; Higgins, K.F.; Thiex, N.; Afton, A.D.
2011-01-01
High concentrations of some hepatic elements might be contributing to the decline of the continental lesser scaup (Aythya affinis) population. We evaluated hepatic element concentrations of male and female lesser scaup collected from the upper Midwest (Iowa, Minnesota, North Dakota, and South Dakota) during the 2003 and 2004 spring migrations. We measured concentrations of 24 elements in livers of 117 lesser scaup. We found that only selenium concentrations were at levels (>3.0 ??g/g wet weight [ww)]) proposed to adversely affect reproduction. Approximately 49% of females (n = 61) had individual hepatic concentrations >3.0 ??g/g ww selenium (Se). Our observed hepatic concentration of Se was similar to that reported in lesser scaup collected from the mid-continental United States but less than Se concentrations reported from the Great Lakes region. We found that the liver cadmium (Cd) concentration for males was significantly higher than that for females. Gender differences in hepatic Cd concentrations have not been previously reported for lesser scaup, but Cd is known to have negative impacts on male reproduction. Our results indicate that lesser scaup migrating through the upper Midwest in spring have elevated Se levels and that males carry a significantly greater Cd burden than females. Moreover, elemental concentrations might be high enough to affect reproduction in both male and female lesser scaup, but controlled laboratory studies are needed to adequately assess the effects of Se and Cd on lesser scaup reproduction. ?? 2010 Springer Science+Business Media, LLC.
Molecular mechanism for cadmium-induced anthocyanin accumulation in Azolla imbricata.
Dai, Ling-Peng; Dong, Xin-Jiao; Ma, Hai-Hu
2012-04-01
Anthocyanins inducibly synthesized by Cd treatment showed high antioxidant activity and might be involved in internal detoxification mechanisms of Azolla imbricata against Cd toxicity. In order to understand anthocyanin biosynthesis mechanism during Cd stress, the cDNAs encoding chalcone synthase (CHS) and dihydroflavonol reductase (DFR), two key enzymes in the anthocyanin synthesis pathway, were isolated from A. imbricata. Deduced amino acid sequences of the cDNAs showed high homology to the sequences from other plants. Expression of AiDFR, and to a lesser extent AiCHS, was significantly induced in Cd treatment plant in comparison with the control. CHS and DFR enzymatic activities showed similar pattern changes with these genes expression during Cd stress. These results strongly indicate that Cd induced anthocyanin accumulation is probably mediated by up-regulation of structural genes including CHS and DFR, which might further increase the activities of enzymes encoded by these structural genes that control the anthocyanin biosynthetic steps. Copyright © 2011 Elsevier Ltd. All rights reserved.
Manolakis, Anastassios C; Kapsoritakis, Andreas N; Kapsoritaki, Anastasia; Tiaka, Elisavet K; Oikonomou, Konstantinos A; Lotis, Vassilis; Vamvakopoulou, Dimitra; Davidi, Ioanna; Vamvakopoulos, Nikolaos; Potamianos, Spyros P
2013-02-01
Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.
CH stretching overtone spectra of trimethyl amine and dimethyl sulfide
NASA Astrophysics Data System (ADS)
Billinghurst, Brant E.; Gough, Kathleen M.; Low, Geoffrey R.; Kjaergaard, Henrik G.
2004-01-01
Trimethyl amine (TMA) exhibits the largest known difference in CH bond lengths within a methyl group, due to what is known as the lone pair trans effect. Dimethyl sulfide also exhibits this effect, but to a far lesser extent, making it ideal for comparison to TMA. In this paper, the first through fourth overtone spectra of N(CH3)3, N(CD3)3, N(CD2H)(CD3)2, N(CH3)(CD3)2, N(CD3)(CH3)2 and S(CH3)2 are reported and all major bands are assigned. The intensities of the observed bands are compared to intensities predicted by the harmonically coupled anharmonic oscillator local mode model. Good correlation is found between the experimental intensities and those predicted with the local mode model and HF/6-311++G(2d,2p) calculated dipole moment functions. An increase in the ability to resolve peaks as methyl groups are deuterated suggests that the lone pair mediates increased coupling between methyl groups.
Neutrophilic infiltration within the airway smooth muscle in patients with COPD
Baraldo, S; Turato, G; Badin, C; Bazzan, E; Beghe, B; Zuin, R; Calabrese, F; Casoni, G; Maestrelli, P; Papi, A; Fabbri, L; Saetta, M
2004-01-01
Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation. PMID:15047950
A cyclodextrin-capped histone deacetylase inhibitor.
Amin, Jahangir; Puglisi, Antonino; Clarke, James; Milton, John; Wang, Minghua; Paranal, Ronald M; Bradner, James E; Spencer, John
2013-06-01
We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission
Gross, Christine; Thoma-Kress, Andrea K.
2016-01-01
The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID:27005656
NASA Astrophysics Data System (ADS)
Isaure, Marie-Pierre; Leyh, Benjamin; Salomé, Murielle; Krauss, Gerd-Joachim; Schaumlöffel, Dirk; Dobritzsch, Dirk
2017-11-01
Aquatic fungi can be used to evaluate the functioning of natural ecosystems. Heliscus lugdunensis is an early colonizer of allochthone leafs. Since this aquatic hyphomycete is able to develop in metal contaminated habitats and tolerates cadmium, it appears to be a good candidate to investigate adaptation to metal pollution. This study aimed at examining the sequestration of Cd in the hyphae of H. lugdunensis, and particularly the role of the tip cells. For that, H. lugdunensis growth was evaluated under various Cd concentrations, and a combination of synchrotron micro X-ray fluorescence and X-ray absorption near edge structure spectroscopy was carried out to determine the compartments of Cd accumulation and the Cd chemical species, respectively. Results showed that the hyphal tip cells were depleted in Cd, and that the metal was stored in older cells. Cd was mainly associated with sulfur ligands and to a lesser extent bound to phosphates and carboxyl/hydroxyl groups from cell wall and/or organic acids. Finally, the aquatic fungus was able to maintain the tip cell as a functional system, thus allowing the colonization of contaminated environments.
Saeedi, Mohsen; Li, Loretta Y; Salmanzadeh, Mahdiyeh
2012-08-15
50 street dust samples from four major streets in eastern and southern Tehran, the capital of Iran, were analyzed for metal pollution (Cu, Cr, Pb, Ni, Cd, Zn, Fe, Mn and Li). Hakanson's method was used to determine the Risk Index (RI) and ecological risks. Amongst these samples, 21 were also analyzed for polycyclic aromatic hydrocarbons (PAHs). Correlation, cluster and principal component analyses identified probable natural and anthropogenic sources of contaminants. The dust had elevated concentrations of Pb, Cd, Cu, Cr, Ni, Zn, Fe and PAHs. Enrichment factors of Cu, Pb, Cd and Zn showed that the dust is extremely enriched in these metals. Multivariate statistical analyses revealed that Cu, Pb, Zn, Fe and PAHs and, to a lesser extent, Cr and Ni have common anthropogenic sources. While Mn and Li were identified to have natural sources, Cd may have different anthropogenic origins. All samples demonstrated high ecological risk. Traffic and related activities, petrogenic and pyrogenic sources are likely to be the main anthropogenic sources of heavy metals and PAHs in Tehran dust. Copyright © 2012 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stadler, K.; Frey, B.; Munoz, L.E.
2009-08-14
Background: Extracorporeal photopheresis is a therapy for treatment of autoimmune diseases, cutaneous T-cell lymphoma, organ graft rejection as well as graft-versus-host diseases. The exact mechanism how the combination of 8-methoxypsoralen plus UV-A irradiation (PUVA) acts is still unclear. We investigated the cell death of activated and non-activated lymphocytes after PUVA treatment as well as the rate of released blebs and their antigen composition. Results: In presence of 8-MOP, UV-A light highly significantly increased the cell death of activated lymphocytes. The same was observed to a lesser extent in non-activated cells. Blebs derived from activated lymphocytes after PUVA treatment showed themore » highest surface exposition of phosphatidylserine. These blebs also displayed a high exposure of the antigens CD5 and CD8 as well as a low exposure of CD28 and CD86. Conclusion: PUVA treatment exerts anti-inflammatory effects by inducing apoptosis and apoptotic cell-derived blebs with immune suppressive surface composition.« less
Keane, N M; Price, P; Lee, S; Stone, S F; French, M A
2001-01-01
This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-γ production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-γ production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-γ production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD. PMID:11678906
Tabak, Benjamin A.; Vrshek-Schallhorn, Suzanne; Zinbarg, Richard E.; Prenoveau, Jason M.; Mineka, Susan; Redei, Eva E.; Adam, Emma K.; Craske, Michelle G.
2015-01-01
Variation in the CD38 gene, which regulates secretion of the neuropeptide oxytocin, has been associated with several social phenotypes. Specifically, rs3796863 A allele carriers have demonstrated increased social sensitivity. In 400 older adolescents, we used trait-state-occasion modeling to investigate how rs3796863 genotype, baseline ratings of chronic interpersonal stress, and their gene-environment (GxE) interaction predicted trait social anxiety and depression symptoms over six years. We found significant GxE effects for CD38 A-carrier genotypes and chronic interpersonal stress at baseline predicting greater social anxiety and depression symptoms. A significant GxE effect of smaller magnitude was also found for C/C genotype and chronic interpersonal stress predicting greater depression; however, this effect was small compared to the main effect of chronic interpersonal stress. Thus, in the context of chronic interpersonal stress, heightened social sensitivity associated with the rs3796863 A allele may prospectively predict risk for social anxiety and (to a lesser extent) depression. PMID:26958455
NASA Astrophysics Data System (ADS)
Breton, Jérôme; Daniel, Catherine; Vignal, Cécile; Body-Malapel, Mathilde; Garat, Anne; Plé, Coline; Foligné, Benoît
2016-01-01
Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.
Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M.; Planer, Shannon L.; Legasse, Alfred W.; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Sodora, Donald L.; Villinger, Francois; Axthelm, Michael K.; Schmitz, Joern E.
2009-01-01
Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production. PMID:19546246
Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik
2014-01-01
Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.
Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.
Orlova-Fink, Nina; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias
2017-10-23
The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.
Sato, Shoko; Hirayama, Koichi; Koyama, Akio; Harano, Teruo; Nagasawa, Toshiro; Ninomiya, Haruhiko
2004-01-01
Pseudoreticulocytosis in a 25-year-old female patient with hemoglobin Köln is reported. The abnormal hemoglobin, hemoglobin Köln (beta chain, Val98-->Met), had previously been confirmed in the patient at the age of 21 years, as well as in her mother, by polymerase chain reaction-based direct sequence analysis of the beta globin gene. The patient underwent splenectomy at the age of 22 years. On her admission to our hospital for treatment of an immunoglobulin A nephropathy, an analysis by an automated hematology analyzer, the Abbott Cell-Dyn 4000 (CD4000), reported a marked reticulocytosis. Staining by the Brecher method with new methylene blue indicated a moderate reticulocytosis (5.7%) of a lesser extent than that indicated by the CD4000 (51.1%). The frequencies of red blood cells (RBC) with Pappenheimer bodies (13.8%), Heinz bodies (32.7%), and Howell-Jolly bodies (0.3%) were increased. The CD4000 detects RBC with RNA fluorescently stained with CD4K530 as reticulocytes. Autofluorescence of RBC with hemoglobin Köln, as we demonstrated by flow cytometry and fluorescent microscopy, was considered to have caused the pseudoreticulocytosis on the fully automated reticulocyte enumeration by the CD4000.
Enhanced Expression of CD13 in Vessels of Inflammatory and Neoplastic Tissues
Matteo, Paola Di; Arrigoni, Gian Luigi; Alberici, Luca; Corti, Angelo; Gallo-Stampino, Corrado; Traversari, Catia; Doglioni, Claudio; Rizzardi, Gian-Paolo
2011-01-01
Aminopeptidase-N (CD13) is an important target of tumor vasculature-targeting drugs. The authors investigated its expression by immunohistochemistry with three anti-CD13 monoclonal antibodies (WM15, 3D8, and BF10) in normal and pathological human tissues, including 58 normal, 32 inflammatory, and 149 tumor tissue specimens. The three antibodies stained vessels in most neoplastic tissues, interestingly with different patterns. As a matter of fact, WM15 stained almost all intratumor and peritumor capillaries and only partially large vessels, whereas BF10 and 3D8 reacted with arteries and venules and to a lesser extent with capillaries. These antibodies also stained the stroma in about half of neoplastic tissues. In inflammatory lesions, the three antibodies stained vessels and stroma, whereas in normal tissues, they stained a small percentage of blood vessels. Finally, the three antibodies failed to stain endothelial cells of normal colon, whereas they reacted with activated human umbilical vein endothelial cells and with endothelial cells of colon adenocarcinoma vessels. Overall, WM15 was the most specific antibody for angiogenic tumor vessels, suggesting that it may be a good tool for detecting the CD13 form associated with the tumor vasculature. This finding may be relevant for CD13-mediated vascular targeting therapies. PMID:21339174
Long, Meixiao; Higgins, Amy D.; Mihalyo, Marianne A.; Adler, Adam J.
2010-01-01
It has recently been shown that effector/memory T cells can undergo peripheral tolerization in response to self-antigen. In the present study, we found that within 24 h self-antigen profoundly impairs the ability of CD4 effectors to express TNF-α (and to a lesser extent IFN-γ); however, several days of self-antigen exposure is required to impair non-effector functions such as IL-2 expression and proliferation. Since only half of the initial effector CD4 cell population expresses effector cytokines following brief antigenic stimulation, tolerization might have been mediated either through functional inactivation of effector-competent cells, or alternatively by the selective deletion of competent and expansion of non-competent cells. When briefly stimulated effectors were fractionated based on their expression of IFN-γ, the IFN-γ− sub-population was able to express IFN-γ following secondary stimulation, indicating that all effector CD4 cells are functionally competent. Furthermore, both IFN-γ+ and IFN-γ− sub-populations underwent tolerization in response to self-HA (although the former was slightly more prone to deletion at later time points). Thus, effector CD4 cell tolerization is mediated primarily through the functional inactivation of effector-competent cells. PMID:14609577
Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M; Planer, Shannon L; Legasse, Alfred W; Sylwester, Andrew W; Piatak, Michael; Lifson, Jeffrey D; Sodora, Donald L; Villinger, Francois; Axthelm, Michael K; Schmitz, Joern E; Picker, Louis J
2009-07-06
Depletion of CD8(+) lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8(+) lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8(+) lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4(+) effector memory T (T(EM)) cells and, to a lesser extent, transitional memory T (T(TrM)) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4(+)/CCR5(+) SIV "target" cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8(+) lymphocytes in SIV(-) RMs led to a sustained increase in the number of potential CD4(+) SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4(+) T(EM) cell proliferation of CD8(+) lymphocyte-depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4(+) T(EM) and T(TrM) cell proliferation, it did not recapitulate the viral dynamics of CD8(+) lymphocyte depletion. These data suggest that CD8(+) lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.
Lapostolle, Véronique; Chevaleyre, Jean; Duchez, Pascale; Rodriguez, Laura; Vlaski-Lafarge, Marija; Sandvig, Ioanna; Brunet de la Grange, Philippe; Ivanovic, Zoran
2018-06-01
Feasibility of ex vivo expansion allows us to consider the steady-state peripheral blood as an alternative source of hematopoietic stem progenitor cells for transplantation when growth factor-induced cell mobilization is contraindicated or inapplicable. Ex vivo expansion dramatically enhances the in vivo reconstituting cell population from steady-state blood. In order to investigate phenotype and the expression of homing molecules, CD34, CD133, CD90, CD45RA, CD26 and CD9 expression was determined on sorted CD34+ cells according to CXCR4 (neg, low, bright) and CD133 expression before and after ex vivo expansion. Hematopoietic stem cell activity was determined in vivo on the basis of hematopoietic repopulation of primary and secondary recipients - NSG immuno-deficient mice. In vivo reconstituting cells in steady-state blood CD34+ cell fraction before expansion belong to the CD133+ population and are CXCR4low or, to a lesser extent, CXCR4neg, while after ex vivo expansion they are contained in only the CD133+CXCR4low cells. The failure of CXCR4bright population to engraft is probably due to the exclusive expression of CD26 by these cells. The limiting-dilution analysis showed that both repopulating cell number and individual proliferative capacity were enhanced by ex vivo expansion. Thus, steady-state peripheral blood cells exhibit a different phenotype compared to mobilized and cord blood ones, as well as to those issued from the bone marrow. This data represent the first phenotypic characterization of steady-state blood cells exhibiting short and long term hematopoietic reconstituting potential, which can be expanded ex vivo, a sine qua non for their subsequent use for transplantation. Copyright © 2018, Ferrata Storti Foundation.
Drent, Esther; Groen, Richard W J; Noort, Willy A; Themeli, Maria; Lammerts van Bueren, Jeroen J; Parren, Paul W H I; Kuball, Jürgen; Sebestyen, Zsolt; Yuan, Huipin; de Bruijn, Joost; van de Donk, Niels W C J; Martens, Anton C M; Lokhorst, Henk M; Mutis, Tuna
2016-05-01
Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody sequences to generate second-generation retroviral CD38-chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite becoming CD38-negative during culture. CD38-chimeric antigen receptor-transduced T cells also displayed significant anti-tumor effects in a xenotransplant model, in which multiple myeloma tumors were grown in a human bone marrow-like microenvironment. CD38-chimeric antigen receptor-transduced T cells also appeared to lyse the CD38(+) fractions of CD34(+) hematopoietic progenitor cells, monocytes, natural killer cells, and to a lesser extent T and B cells but did not inhibit the outgrowth of progenitor cells into various myeloid lineages and, furthermore, were effectively controllable with a caspase-9-based suicide gene. These results signify the potential importance of CD38-chimeric antigen receptor-transduced T cells as therapeutic tools for CD38(+) malignancies and warrant further efforts to diminish the undesired effects of this immunotherapy using appropriate strategies. Copyright© Ferrata Storti Foundation.
1945-02-01
found t; a great extent on thn ueed cylinder barrel ( SAE 4140 steel) and to a lesser extent on the top ohrmne- plated ring of the aesembl.yafter it had...on the used cylinder barrel (W 4140 steel) used in the tests and, to a lesser extent, on the used top chrome-platedring of the piston assembly. The
Gaspéri, Johnny; Ayrault, Sophie; Moreau-Guigon, Elodie; Alliot, Fabrice; Labadie, Pierre; Budzinski, Hélène; Blanchard, Martine; Muresan, Bogdan; Caupos, Emilie; Cladière, Mathieu; Gateuille, David; Tassin, Bruno; Bordier, Louise; Teil, Marie-Jeanne; Bourges, Catherine; Desportes, Annie; Chevreuil, Marc; Moilleron, Régis
2016-11-10
Soils are playing a central role in the transfer and accumulation of anthropogenic pollutants in urbanized regions. Hence, this study aimed at examining the contamination levels of selected soils collected within and around the Paris conurbation (France). This also evaluated factors controlling contamination. Twenty-three trace and major elements as well as 82 organic micropollutants including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), phthalates (PAEs), polybrominated diphenyl ethers (PBDEs), alkylphenols (APs), and perfluoroalkylated substances (PFASs) were analyzed. Results reinforced the concern raised by the occurrence and levels of metals such as Zn, Pb, Cu, and Hg, identified as metallic markers of anthropogenic activities, but also pointed out the ubiquitous contamination of soils by organic micropollutants in the 0.2-55,000-μg/kg dw range. For well-documented compounds like PAHs, PCBs, and to a lesser extent PBDEs, contents were in the range of background levels worldwide. The pollutant stock in tested soil was compared to the annual atmospheric input. For PAHs; Pb; and to a lesser extent Zn, Cu, Cd, Hg, Sb, PAEs, and APs, a significant stock was observed, far more important than the recent annual atmospheric fluxes. This resulted from both (i) the persistence of a fraction of pollutants in surface soils and (ii) the cumulative atmospheric inputs over several decades. Regarding PBDEs and PFASs, stronger atmospheric input contributions were observed, thereby highlighting their recent dispersal into the environment.
Stimulatory role of interleukin 10 in CD8+ T cells through STATs in gastric cancer.
Xi, Jianjun; Xu, Mingzheng; Song, Zongchang; Li, Hongqiang; Xu, Shumin; Wang, Chunmei; Song, Haihan; Bai, Jianwen
2017-05-01
CD8 + T cells are considered to be critical in tumor surveillance and elimination. Increased CD8 + T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8 + T cell-mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8 + T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II-IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10-expressing cells in both CD4 + and CD8 + T cells compared to healthy controls. But distinctive from the interleukin 10-expressing CD4 + T cells, which increased in frequency in advanced cancer, the interleukin 10-expressing CD8 + T cells did not increase with cancer stage in the peripheral blood and actually decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10 receptor expression was also enriched in interferon gamma-expressing activated CD8 + T cells. Compared to interleukin 10-nonexpressing CD8 + T cells, interleukin 10 receptor-expressing CD8 + T cells secreted significantly elevated interferon gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8 + T cells with interleukin 10 alone could significantly enhance CD8 + T cell survival, an effect dependent on interleukin 10 receptor expression. Interleukin 10 also increased CD8 + T cell proliferation synergistically with interferon gamma but not alone. Analysis of downstream signal transducer and activator of transcription molecules showed that interleukin 10 treatment significantly increased the phosphorylation of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 1 to lesser extent. Together, these results demonstrate that interleukin 10 possessed stimulatory roles in activated CD8 + T cells from gastric cancer patients.
Evolution of oxygenated cadmium sulfide (CdS:O) during high-temperature CdTe solar cell fabrication
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meysing, Daniel M.; Reese, Matthew O.; Warren, Charles W.
Oxygenated cadmium sulfide (CdS:O) produced by reactive sputtering has emerged as a promising alternative to conventional CdS for use as the n-type window layer in CdTe solar cells. Here, complementary techniques are used to expose the window layer (CdS or CdS:O) in completed superstrate devices and combined with a suite of materials characterization to elucidate its evolution during high temperature device processing. During device fabrication amorphous CdS:O undergoes significant interdiffusion with CdTe and recrystallization, forming CdS1-yTey nanocrystals whose Te fraction approaches solubility limits. Significant oxygen remains after processing, concentrated in sulfate clusters dispersed among the CdS1-yTey alloy phase, accounting formore » ~30% of the post-processed window layer based on cross-sectional microscopy. Interdiffusion and recrystallization are observed in devices with un-oxygenated CdS, but to a much lesser extent. Etching experiments suggest that the CdS thickness is minimally changed during processing, but the CdS:O window layer is reduced from 100 nm to 60-80 nm, which is confirmed by microscopy. Alloying reduces the band gap of the CdS:O window layer to 2.15 eV, but reductions in thickness and areal density improve its transmission spectrum, which is well matched to device quantum efficiency. The changes to the window layer in the reactive environments of device fabrication are profoundly different than what occurs by thermal annealing in an inert environment, which produced films with a band gap of 2.4 eV for both CdS and CdS:O. These results illustrate for the first time the significant changes that occur to the window layer during processing that are critical to the performance of CdTe solar cells.« less
Esch, Kevin J; Juelsgaard, Rachel; Martinez, Pedro A; Jones, Douglas E; Petersen, Christine A
2013-12-01
Control of Leishmania infantum infection is dependent upon Th1 CD4(+) T cells to promote macrophage intracellular clearance of parasites. Deficient CD4(+) T cell effector responses during clinical visceral leishmaniasis (VL) are associated with elevated production of IL-10. In the primary domestic reservoir of VL, dogs, we define occurrence of both CD4(+) and CD8(+) T cell exhaustion as a significant stepwise loss of Ag-specific proliferation and IFN-γ production, corresponding to increasing VL symptoms. Exhaustion was associated with a 4-fold increase in the population of T cells with surface expression of programmed death 1 (PD-1) between control and symptomatic populations. Importantly, exhausted populations of CD8(+) T cells and to a lesser extent CD4(+) T cells were present prior to onset of clinical VL. VL-exhausted T cells did not undergo significant apoptosis ex vivo after Ag stimulation. Ab block of PD-1 ligand, B7.H1, promoted return of CD4(+) and CD8(+) T cell function and dramatically increased reactive oxygen species production in cocultured monocyte-derived phagocytes. As a result, these phagocytes had decreased parasite load. To our knowledge, we demonstrate for the first time that pan-T cell, PD-1-mediated, exhaustion during VL influenced macrophage-reactive oxygen intermediate production. Blockade of the PD-1 pathway improved the ability of phagocytes isolated from dogs presenting with clinical VL to clear intracellular parasites. T cell exhaustion during symptomatic canine leishmaniasis has implications for the response to vaccination and therapeutic strategies for control of Leishmania infantum in this important reservoir species.
Guney, Mert; Zagury, Gerald J
2013-06-04
Toys and children's jewelry may contain metals to which children can be orally exposed. The objectives of this research were (1) to determine total concentrations (TC's) of As, Ba, Cd, Cr, Cu, Mn, Ni, Pb, Sb, and Se in toys and jewelry (n = 72) bought on the North American market and compare TC's to regulatory limits, and (2) to estimate oral metal bioavailability in selected items (n = 4) via bioaccessibility testing. For metallic toys and children's jewelry (n = 24) 20 items had TC's exceeding migratable concentration limits (European Union). Seven of seventeen jewelry items did not comply with TC limits in U.S. and Canadian regulations. Samples included articles with very high Cd (37% [w/w]), Pb (65%), and Cu (71%) concentrations. For plastic toys (n = 18), toys with paint or coating (n = 12), and brittle or pliable toys (n = 18), TC's were below the EU migration limits (except in one toy for each category). Bioaccessibility tests showed that a tested jewelry item strongly leached Pb (gastric: 698 μg, intestinal: 705 μg) and some Cd (1.38 and 1.42 μg). Especially in metallic toys and jewelry, contamination by Pb and Cd, and to a lesser extent by Cu, Ni, As, and Sb, still poses an acute problem in North America.
Ardestani, Masoud M; Ortiz, Maria Diez; van Gestel, Cornelis A M
2013-08-01
The present study sought to quantify the components of a biotic ligand model (BLM) for the effects of Cd on Folsomia candida (Collembola). Assuming that soil porewater is the main route of exposure and to exclude the effects of soil particles on metal availability, animals were exposed for 7 d to different Cd concentrations between 0.1 mM and 100 mM in simplified soil solutions at different Ca concentrations (0.2 mM, 0.8 mM, 3.2 mM, and 12.8 mM) or at different pH (5.0, 6.0, and 7.0). Higher Ca concentrations decreased the toxicity of Cd (adult survival) in test solutions, whereas toxicity was slightly lower at pH 7 and 6 than at pH 5, suggesting a mitigating effect of Ca and to a lesser extent pH on Cd toxicity to F. candida. Internal Cd concentrations in the animals increased with increasing exposure level but were significantly reduced by increasing Ca concentrations and were not significantly affected by pH. By using Langmuir isotherms, binding constants for Cd, Ca, and protons and the fraction of binding sites occupied by Cd were calculated and used to predict effects of Cd on survival. Predicted toxicity showed a good agreement with measured responses when Ca and pH were used as separate factors or combined together. The present study shows indications of protective effects of Ca but less of protons on the toxicity and uptake of Cd in F. candida on exposure to simplified soil solutions, which can be described using the principles of a biotic ligand model. Copyright © 2013 SETAC.
Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Forghieri, Fabio; Zanetti, Eleonora; Quadrelli, Chiara; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Paolini, Ambra; Maccaferri, Monica; Del Giovane, Cinzia; D'Amico, Roberto; Rumpianesi, Fabio; Pecorari, Monica; Cavalleri, Francesca; Marasca, Roberto; Narni, Franco; Luppi, Mario
2011-11-17
Mucorales-specific T cells were investigated in 28 hematologic patients during the course of their treatment. Three developed proven invasive mucormycosis (IM), 17 had infections of known origin but other than IM, and 8 never had fever during the period of observation. Mucorales-specific T cells could be detected only in patients with IM, both at diagnosis and throughout the entire course of the IM, but neither before nor for long after resolution of the infection. Such T cells predominantly produced IL-4, IFN-γ, IL-10, and to a lesser extent IL-17 and belonged to either CD4(+) or CD8(+) subsets. The specific T cells that produced IFN-γ were able to directly induce damage to Mucorales hyphae. None of the 25 patients without IM had Mucorales-specific T cells. Specific T cells contribute to human immune responses against fungi of the order Mucorales and could be evaluated as a surrogate diagnostic marker of IM.
Selleri, Silvia; Dieng, Mame Massar; Nicoletti, Simon; Louis, Isabelle; Beausejour, Christian; Le Deist, Françoise
2013-01-01
The mechanisms by which mesenchymal stromal cells (MSCs) induce immunomodulation are still poorly understood. In the current work, we show by a combination of polymerase chain reaction (PCR) array, flow cytometry, and multiplex cytokine data analysis that during the inhibition of an alloantigen-driven CD4+ T-cell response, MSCs induce a fraction of CD4+ T-cells to coexpress interferon-γ (IFNγ) and interleukin-10 (IL-10). This CD4+ IFNγ+ IL-10+ cell population shares properties with recently described T-cells originating from switched Th1 cells that start producing IL-10 and acquire a regulatory function. Here we report that IL-10-producing Th1 cells accumulated with time during T-cell stimulation in the presence of MSCs. Moreover, MSCs caused stimulated T-cells to downregulate the IFNγ receptor (IFNγR) without affecting IL-10 receptor expression. Further, the inhibitory effect of MSCs could be reversed by an anti-IFNγR-blocking antibody, indicating that IFNγ is one of the major players in MSC-induced T-cell suppression. Stimulated (and, to a lesser extent, resting) CD4+ T-cells treated with MSCs were able to inhibit the proliferation of autologous CD4+ T-cells, demonstrating their acquired regulatory properties. Altogether, our results suggest that the generation of IL-10-producing Th1 cells is one of the mechanisms by which MSCs can downmodulate an immune response. PMID:23167734
Impact of representation of hydraulic structures in modelling a Severn barrage
NASA Astrophysics Data System (ADS)
Bray, Samuel; Ahmadian, Reza; Falconer, Roger A.
2016-04-01
In this study, enhancements to the numerical representation of sluice gates and turbines were made to the hydro-environmental model Environmental Fluid Dynamics Code (EFDC), and applied to the Severn Tidal Power Group Cardiff-Weston Barrage. The extended domain of the EFDC Continental Shelf Model (CSM) allows far-field hydrodynamic impact assessment of the Severn Barrage, pre- and post-enhancement, to demonstrate the importance of accurate hydraulic structure representation. The enhancements were found to significantly affect peak water levels in the Bristol Channel, reducing levels by nearly 1 m in some areas, and even affect predictions as far-field as the West Coast of Scotland, albeit to a far lesser extent. The model was tested for sensitivity to changes in the discharge coefficient, Cd, used in calculating discharge through sluice gates and turbines. It was found that the performance of the Severn Barrage is not sensitive to changes to the Cd value, and is mitigated through the continual, rather than instantaneous, discharge across the structure. The EFDC CSM can now be said to be more accurately predicting the impacts of tidal range proposals, and the investigation of sensitivity to Cd improves the confidence in the modelling results, despite the uncertainty in this coefficient.
Kuhn, Chantal; Rezende, Rafael Machado; M'Hamdi, Hanane; da Cunha, Andre Pires; Weiner, Howard L.
2016-01-01
Oral administration of antigen induces regulatory T cells that express latent membrane-bound TGF-beta (LAP) and that have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP+ on CD4+ T cells. The combination of anti-CD3 mAb, anti-CD28 mAb and recombinant IL-2 induced expression of LAP on naïve CD4+ T cells, independent of FoxP3 or exogenous TGF-β. In vitro generated CD4+LAP+FoxP3− T cells were suppressive in vitro, inhibiting proliferation of naïve CD4+ T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing antibodies against cytokines we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNFα. IL-6 abrogated the in vitro induction of CD4+LAP+ T cells by STAT3 dependent inhibition of Lrrc32 (GARP), the adapter protein that tethers TGF-beta to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4+ T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that pro-inflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases. PMID:28039301
Kuhn, Chantal; Rezende, Rafael Machado; M'Hamdi, Hanane; da Cunha, Andre Pires; Weiner, Howard L
2017-02-01
Oral administration of Ag induces regulatory T cells that express latent membrane-bound TGF-β (latency-associated peptide [LAP]) and have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP + on CD4 + T cells. The combination of anti-CD3 mAb, anti-CD28 mAb, and recombinant IL-2 induced expression of LAP on naive CD4 + T cells, independent of Foxp3 or exogenous TGF-β. In vitro generated CD4 + LAP + Foxp3 - T cells were suppressive in vitro, inhibiting proliferation of naive CD4 + T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing Abs against cytokines, we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNF-α. IL-6 abrogated the in vitro induction of CD4 + LAP + T cells by STAT3-dependent inhibition of Lrrc32 (glycoprotein A repetitions predominant [GARP]), the adapter protein that tethers TGF-β to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4 + T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that proinflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.
Li, Changlin; Wang, Yibing; Gao, Li; Zhang, Jingsong; Shao, Jie; Wang, Shengnian; Feng, Weiguo; Wang, Xingyu; Li, Minglie; Chang, Zongliang
2002-01-01
Macrophages form a crucial bridge between the innate and adaptive immune response. One of their most important functions is to recognize infectious microorganisms. Toll-like receptors (TLRs) are key elements in pathogen recognition, and among them, TLR2 and TLR4 are most discussed. However, expression patterns of TLRs during myeloid cell differentiation to macrophage are unknown. In this study, we examined differentiation in the model human myeloid cell line, HL-60, treated with phorbol 12-myristate 13-acetate (PMA) or VitD(3). Expression of TLR2, TLR4, and CD14 were measured by reverse transcription-PCR, RNase protection assay, and fluorescence-activated cell sorter assays. After treatment by PMA (1, 10, and 100 nM) for 12, 24, and 48 h, expression of TLR2 and CD14 mRNA was increased in a time- and dose-dependent manner. However, VitD(3) only induced expression of CD14 but not TLR2 in HL-60 cells. TLR4 was expressed constitutively before differentiation and increased slightly after that. Thus, PMA-mediated differentiation of HL-60 cells to macrophages is associated largely with TLR2 expression and, to a much lesser extent, with TLR4. Furthermore, up-regulation of TLR2 and CD14 mRNA expression by PMA was abrogated by a protein kinase C inhibitor, Calphostine C, suggesting the up-regulation of TLR2 and CD14 mRNA is dependent on the activation of protein kinase C. Coexpression of CD14/TLR2 and/or CD14/TLR4 may be essential but not sufficient for the production of tumor necrosis factor-alpha in response to lipopolysaccharide in our system.
Collaboration between tumor-specific CD4+ T cells and B cells in anti-cancer immunity.
Guy, Thomas V; Terry, Alexandra M; Bolton, Holly A; Hancock, David G; Zhu, Erhua; Brink, Robert; McGuire, Helen M; Shklovskaya, Elena; Fazekas de St. Groth, Barbara
2016-05-24
The role of B cells and antibodies in anti-tumor immunity is controversial, with both positive and negative effects reported in animal models and clinical studies. We developed a murine B16.F10 melanoma model to study the effects of collaboration between tumor-specific CD4+ T cells and B cells on tumor control. By incorporating T cell receptor transgenic T cells and B cell receptor isotype switching B cells, we were able to track the responses of tumor-reactive T and B cells and the development of anti-tumor antibodies in vivo. In the presence of tumor-specific B cells, the number of tumor-reactive CD4+ T cells was reduced in lymphoid tissues and the tumor itself, and this correlated with poor tumor control. B cells had little effect on the Th1 bias of the CD4+ T cell response, and the number of induced FoxP3+ regulatory cells (iTregs) generated from within the original naive CD4+ T cell inoculum was unrelated to the degree of B cell expansion. In response to CD4+ T cell help, B cells produced a range of isotype-switched anti-tumor antibodies, principally IgG1, IgG2a/c and IgG2b. In the absence of CD4+ T cells, B cells responded to agonistic anti-CD40 administration by switching to production of IgG2a/c and, to a lesser extent, IgG1, IgG3, IgA and IgE, which reduced the number of lung metastases after i.v. tumor inoculation but had no effect on the growth of subcutaneous tumors.
George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash
2014-01-01
Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4+ and CD8+ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections—Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4+ and CD8+ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial–specific frequencies of mono- and multi–functional CD4+ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4+ and CD8+ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4+ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4+ Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4+ T cell responses as well as protective systemic cytokine responses in active pulmonary TB. PMID:25211342
Copper, zinc, and cadmium in various fractions of soil and fungi in a Swedish forest.
Vinichuk, Mykhailo M
2013-01-01
Ectomycorrhizal fungi profoundly affect forest ecosystems through mediating nutrient uptake and maintaining forest food webs. The accumulation of metals in each transfer step from bulk soil to fungal sporocarps is not well known. The accumulation of three metals copper (Cu), zinc (Zn) and cadmium (Cd) in bulk soil, rhizosphere, soil-root interface, fungal mycelium and sporocarps of mycorrhizal fungi in a Swedish forest were compared. Concentrations of all three metals increased in the order: bulk soil < soil-root interface (or rhizosphere) < fungal mycelium < fungal sporocarps. The uptake of Cu, Zn and Cd during the entire transfer process in natural conditions between soil and sporocarps occurred against a concentration gradient. In fungal mycelium, the concentration of all three metals was about three times higher than in bulk soil, and the concentration in sporocarps was about two times higher than in mycelium. In terms of accumulation, fungi (mycelium and sporocarps) preferred Cd to Zn and Cu. Zinc concentration in sporocarps and to a lesser extent in mycelium depended on the concentration in soil, whereas, the uptake of Cu and Cd by both sporocarps and mycelium did not correlate with metal concentration in soil. Heavy metal accumulation within the fungal mycelium biomass in the top forest soil layer (0-5 cm) might account for ca. 5-9% of the total amount of Cu, 5-11% of Zn, and 16-32% of Cd. As the uptake of zinc and copper by fungi may be balanced, this implied similarities in the uptake mechanism.
Castro-Manrreza, Marta E.; Mayani, Hector; Monroy-García, Alberto; Flores-Figueroa, Eugenia; Chávez-Rueda, Karina; Legorreta-Haquet, Victoria; Santiago-Osorio, Edelmiro
2014-01-01
Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM—the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BM-MSCs and UCB-MSCs significantly inhibited the proliferation of both CD4+ and CD8+ activated T cells in a cell–cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-γ, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4+CD25+CTLA-4+. Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications. PMID:24428376
Mascarell, L; Rak, S; Worm, M; Melac, M; Soulie, S; Lescaille, G; Lemoine, F; Jospin, F; Paul, S; Caplier, L; Hasséus, B; Björhn, C; Zeldin, R K; Baron-Bodo, V; Moingeon, P
2015-04-01
A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey S; Hwu, Patrick; Radvanyi, Laszlo G
2011-04-01
Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.
Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C.; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey; Hwu, Patrick; Radvanyi, Laszlo
2011-01-01
Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose IL-2 is a promising form of immunotherapy for Stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8+ T cells to differentiate into effector cells losing key co-stimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8+ TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative co-stimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Post-REP TIL were found to be highly sensitive to activation-induced cell death (AICD) when re-activated through the TCR with low levels of OKT3 antibody. However, co-ligation of 4-1BB using two different agonistic anti-4-1BB antibodies potently prevented AICD of post-REP CD8+ TIL, including those specific for MART-1, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB-co-stimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced CTL activity against melanoma cells. Lastly, post-REP CD8+ TIL were protected from cell death by anti-4-1BB ligation when exposed to HLA-matched melanoma cells. Our results indicate that 4-1BB co-stimulation may significantly improve TIL survival during melanoma ACT and boost anti-tumor cytolytic activity. PMID:21389874
Custer, T.W.; Custer, Christine M.; Hines, R.K.; Sparks, D.W.
2000-01-01
During the winter of 1993a??94, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal (IHC), East Chicago, IN, USA, and examined for tissue contaminant levels. Lesser scaup collected on the IHC had higher concentrations of cadmium (Cd), mercury (Hg), selenium (Se), polychlorinated biphenyls (PCBs), selected organchlorine pesticides, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polycyclic aromatic hydrocarbons, and aliphatic hydrocarbons than reference birds. Of the scaup collected on the IHC, 44% had Cd concentrations in the liver considered above background for freshwater waterfowl (>3 I?g/g dry wt.), 50% had Se concentrations in the liver above a level possibly harmful to the health of young and adult birds (>33 I?g/g dry wt.), and 88% of the scaup carcasses exceeded the PCB human consumption guidelines for edible poultry in the USA (>3.0 I?g/g lipid wt.). The ratio of pristane:n-heptadecane concentrations in 47% of lesser scaup collected on IHC was elevated above 1.0, which is indicative of chronic exposure to petroleum hydrocarbons. Copyright A? 2009 Elsevier B.V.
Custer, T W; Custer, C M; Hines, R K; Sparks, D W
2000-12-01
During the winter of 1993-94, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal (IHC), East Chicago, IN, USA, and examined for tissue contaminant levels. Lesser scaup collected on the IHC had higher concentrations of cadmium (Cd), mercury (Hg), selenium (Se), polychlorinated biphenyls (PCBs), selected organchlorine pesticides, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polycyclic aromatic hydrocarbons, and aliphatic hydrocarbons than reference birds. Of the scaup collected on the IHC, 44% had Cd concentrations in the liver considered above background for freshwater waterfowl (>3 microg/g dry wt.), 50% had Se concentrations in the liver above a level possibly harmful to the health of young and adult birds (>33 microg/g dry wt.), and 88% of the scaup carcasses exceeded the PCB human consumption guidelines for edible poultry in the USA (>3.0 microg/g lipid wt.). The ratio of pristane:n-heptadecane concentrations in 47% of lesser scaup collected on IHC was elevated above 1.0, which is indicative of chronic exposure to petroleum hydrocarbons.
Ciazela, Jakub; Siepak, Marcin
2016-06-01
We determined the Cd, Cr, Cu, Ni, Pb, and Zn concentrations in soil samples collected along the eight main outlet roads of Poznań. Samples were collected at distances of 1, 5, and 10 m from the roadway edges at depth intervals of 0-20 and 40-60 cm. The metal content was determined in seven grain size fractions. The highest metal concentrations were observed in the smallest fraction (<0.063 mm), which were up to four times higher than those in sand fractions. Soil Pb, Cu, and Zn (and to a lesser extent Ni, Cr, and Cd) all increased in relation to the geochemical background. At most sampling sites, metal concentrations decreased with increasing distance from roadway edges and increasing depth. In some locations, the accumulation of metals in soils appears to be strongly influenced by wind direction. Our survey findings should contribute in predicting the behavior of metals along outlet road, which is important by assessing sources for further migration of heavy metals into the groundwater, plants, and humans.
Fabbiano, Salvatore; Menacho-Márquez, Mauricio; Robles-Valero, Javier; Pericacho, Miguel; Matesanz-Marín, Adela; García-Macías, Carmen; Sevilla, María A; Montero, M J; Alarcón, Balbino; López-Novoa, José M; Martín, Pilar; Bustelo, Xosé R
2015-10-01
Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39(+) regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
NASA Astrophysics Data System (ADS)
Othmani, M. A.; Soussi, F.; Ferreira da Silva, E.; Moussi, A.; Oueslati, W.; Jebali, R.
2012-04-01
The former mining district of Touiref (1901-1958), located North-West of Tunisia, and where the activities have stopped 50 years ago, gave rise to large volumes of mine (extraction, flotation) tailings containing sulphides (galena, sphalerite, jordanite, pyrite, marcasite) associated with a carbonate gangue. Analysis of a hundred samples of soil has been used to develop isoconcentration maps of Pb, Zn, Cd and As across the study area, beyond the local geochemical background (LGB). The drawing of these maps has allowed the delineation of the contaminated areas using Geographic Information Systems (GIS). In addition, the soils of the study area were characterized in terms physico-chemical (pH and Corg), grain size, mineralogical and chemical means. Their neutral to slightly alkaline pH is (7.91 to 8.81), and their clay (32 and 57%)-silt (26 and 42%) texture, are characteristic of soils developed on carbonate bedrocks. The percentages in organic carbon (Corg) are between 0.71 and 5.6%. From a mineralogical point of view, mainly Pb-Fe sulphides associated with their alteration products have been observed within these soils. The levels of Pb, Zn, Cd and As, may go up 0.99%, 1.99%, 140 ppm and 409 ppm, respectively. These high concentrations were recorded around the extraction, processing and storage sites on the one hand and through the flood zones and the prevailing wind direction (NW-SSE) on the other. These soils have also been subjected to sequential extraction tests in order to characterize the metal-bearing phases and assess the mobility and bioavailability of heavy metals. The results have shown that Pb is mainly associated with the acid-soluble fraction (carbonates) and to a lesser extent with the Fe-(oxy)hydroxides, whereas Zn and Cd are mainly associated with Fe-(oxy)hydroxides and to a lesser degree with sulphides. Metals associated with these phases can be easily mobilized in response to physico-chemical changes and become phytoaccessible.
Formulation and Physical Properties of Cyanate Ester Nanocomposites Based on Graphene
2014-03-01
during cure. The addition of GO, and, to a lesser extent, TRGO, resulted in improved mechanical properties, particularly fracture toughness, with the...a lesser extent, TRGO, resulted in improved mechanical proper- ties, particularly fracture toughness, with the addition of TRGO having a modestly...LECy. However, the mechanism of fracture toughness improvement may be different with each form of graphene. In the case of GO, the high degree of oxi
Hartman, Deborah S; Tracey, Daniel E; Lemos, Brenda R; Erlich, Emma C; Burton, Randall E; Keane, David M; Patel, Rutvij; Kim, Skaison; Bhol, Kailash C; Harris, M Scott; Fox, Barbara S
2016-06-01
AVX-470 is an orally administered, bovine-derived, anti-tumour necrosis factor (TNF) antibody with local activity in the gastrointestinal tract. In the first-in-human clinical trial of AVX-470 in active ulcerative colitis, we evaluated inflammatory biomarkers in colon tissue as measures of disease activity and early response to treatment. Thirty-six patients received active drug (AVX-470 at 0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Colon biopsy samples were collected from 5 regions of colon at baseline and week 4. Tissue inflammatory biomarkers were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), epithelial cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and bovine immunoglobulin by immunohistochemistry and mass spectrometry. Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]) at colonoscopy was assessed in each colonic region by a central reader. Bovine immunoglobulin was observed in mucosal tissue before and after dosing in lamina propria and submucosal layers of biopsy tissue. Baseline levels of TNF, myeloperoxidase (MPO), CD68 and interleukin (IL)-1β and, to a lesser extent, IL-6 mRNA were 2- to 3-fold higher in distal vs proximal colon tissue, corresponding to the 2- to 3-fold differences in baseline severities of endoscopic scores. Reductions of >10-fold in TNF and, to lesser extents, in MPO and epithelial cell apoptosis were observed in proximal and distal colon biopsies after 4 weeks of AVX-470 3.5g/day treatment. Reductions in TNF scores were correlated with changes in MPO and CD3 immunohistochemistry scores. These results are consistent with anti-TNF activity of orally administered AVX-470 in colon mucosal tissue in ulcerative colitis patients and demonstrate the utility of tissue biomarkers in assessing disease and treatment response in early clinical studies. This trial was registered with Clinicaltrials.gov as study NCT01759056 and with EudraCT as study 2012-004859-27. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Upadhyay, Ravi K; Rohatgi, Leena; Chaubey, Mukesh K; Jain, Subhash C
2006-12-27
Extracts of Capparis decidua stems and flowers showed insecticidal and oviposition inhibitory activities against Bruchus chinensis. The LC50 values of these extracts were found to increase with the increase in the polarity of the extract at different exposure periods. For instance, after 96 h, the LC50 values were found to be 3.619, 7.319, and 10.151 microg for CD1, CD2, and CD3, respectively. Extract CD7 was effective only at higher doses. The toxicity was found to be dose- and time-dependent. The females laid lesser number of eggs, when exposed to sublethal doses of different extracts and pure compounds, as compared to control. The maximum oviposition deterrence index was found for extract CD1 followed in decreasing order by CD2, CD3, and CD7. From extract CD1, two compounds were isolated and characterized as triacontanol (C1) and 2-carboxy-1,1-dimethylpyrrolidine (C2). When the females were exposed to sublethal doses of these compounds, they laid lesser number of eggs as compared to the control. C2 was found to have a slightly greater oviposition inhibition effect than C1. From fraction CD7, one novel compound labeled as CDF1 has been isolated and identified as 6-(1-hydroxy-non-3-enyl)tetrahydropyran-2-one. CDF1 has also shown insecticidal and oviposition inhibitory activities against B. chinensis at low concentrations.
Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Lackner, Andrew A.
2013-01-01
Although increased lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been reported in blood, there is little information on cell turnover in tissues, particularly in primary SIV infection. Here we examined the levels of proliferating T cell subsets in mucosal and peripheral lymphoid tissues of adult macaques throughout SIV infection. To specifically label cells in S-phase division, all animals were inoculated with bromodeoxyuridine 24 h prior to sampling. In healthy macaques, the highest levels of proliferating CD4+ and CD8+ T cells were in blood and, to a lesser extent, in spleen. Substantial percentages of proliferating cells were also found in intestinal tissues, including the jejunum, ileum, and colon, but very few proliferating cells were detected in lymph nodes (axillary and mesenteric). Moreover, essentially all proliferating T cells in uninfected animals coexpressed CD95 and many coexpressed CCR5 in the tissues examined. Confocal microscopy also demonstrated that proliferating cells were substantial viral target cells for SIV infection and viral replication. After acute SIV infection, percentages of proliferating CD4+ and CD8+ T cells were significantly higher in tissues of chronically infected macaques and macaques with AIDS than in those of the controls. Surprisingly, however, we found that proliferating CD4+ T cells were selectively decreased in very early infection (8 to 10 days postinoculation [dpi]). In contrast, levels of proliferating CD8+ T cells rapidly increased after SIV infection, peaked by 13 to 21 dpi, and thereafter remained significantly higher than those in the controls. Taken together, these findings suggest that SIV selectively infects and destroys dividing, nonspecific CD4+ T cells in acute infection, resulting in homeostatic changes and perhaps continuing loss of replication capacity to respond to nonspecific and, later, SIV-specific antigens. PMID:23596288
Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Lackner, Andrew A; Veazey, Ronald S
2013-06-01
Although increased lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been reported in blood, there is little information on cell turnover in tissues, particularly in primary SIV infection. Here we examined the levels of proliferating T cell subsets in mucosal and peripheral lymphoid tissues of adult macaques throughout SIV infection. To specifically label cells in S-phase division, all animals were inoculated with bromodeoxyuridine 24 h prior to sampling. In healthy macaques, the highest levels of proliferating CD4(+) and CD8(+) T cells were in blood and, to a lesser extent, in spleen. Substantial percentages of proliferating cells were also found in intestinal tissues, including the jejunum, ileum, and colon, but very few proliferating cells were detected in lymph nodes (axillary and mesenteric). Moreover, essentially all proliferating T cells in uninfected animals coexpressed CD95 and many coexpressed CCR5 in the tissues examined. Confocal microscopy also demonstrated that proliferating cells were substantial viral target cells for SIV infection and viral replication. After acute SIV infection, percentages of proliferating CD4(+) and CD8(+) T cells were significantly higher in tissues of chronically infected macaques and macaques with AIDS than in those of the controls. Surprisingly, however, we found that proliferating CD4(+) T cells were selectively decreased in very early infection (8 to 10 days postinoculation [dpi]). In contrast, levels of proliferating CD8(+) T cells rapidly increased after SIV infection, peaked by 13 to 21 dpi, and thereafter remained significantly higher than those in the controls. Taken together, these findings suggest that SIV selectively infects and destroys dividing, nonspecific CD4(+) T cells in acute infection, resulting in homeostatic changes and perhaps continuing loss of replication capacity to respond to nonspecific and, later, SIV-specific antigens.
Fismes, Joëlle; Echevarria, Guillaume; Leclerc-Cessac, Elisabeth; Morel, Jean Louis
2005-01-01
Knowledge of radionuclide or trace element retention and translocation to plants following an aerial contamination event, for example, sprinkling with contaminated water, is necessary for the evaluation of human exposure through consumption of contaminated vegetables. The fate of 63Ni and 109Cd in all plant parts of three different vegetables after wet deposition on leaves or on fruits was studied. Lettuce (Lactuca sativa L.), radish (Raphanus sativus L.), and bean (Phaseolus vulgaris L.) grown under controlled conditions in a growth chamber were contaminated with 63Ni and 109Cd either on leaves, by means of two different contamination methods (a single early contamination and a repetitive one), or on bean husks (third contamination method: a single contamination at a late stage). Spiked and nonspiked organs were harvested at maturity and radionuclide contents were measured. The fraction retained was on average 56% of the initially administered doses of 63Ni and 87% of 109Cd. The leaf-to-other organ translocation factor was considerably higher for 63Ni (on average 43% of retained radioactivity) than for 109Cd (8%). Nickel-63 migrated throughout the whole plant following foliar contamination, and mainly toward young leaves, seeds in formation, and sink organs, whereas 109Cd migrated to a much lesser extent and only to the organs that were closest to the spiked one, and not at all into fruit. After a fruit contamination event, both radionuclides were translocated into the seeds of spiked fruits. Radionuclide retention and translocation were not affected by plant species, but principally by the type of organ contaminated.
Ziebolz, D; Jahn, C; Pegel, J; Semper-Pinnecke, E; Mausberg, R F; Waldmann-Beushausen, R; Schöndube, F A; Danner, B C
2018-01-15
The aim of the study was to detect periodontal pathogens DNA in atrial and myocardial tissue, and to investigate periodontal status and their connection to cardiac tissue inflammation. In 30 patients, biopsy samples were taken from the atrium (A) and the ventricle myocardium (M) during aortic valve surgery. The dental examination included the dental and periodontal status (PS) and a collection of a microbiological sample. The detection of 11 periodontal pathogens DNA in oral and heart samples was carried out using PCR. The heart samples were prepared for detecting the LPS-binding protein (LBP), and for inflammation scoring on immunohistochemistry (IHC), comprising macrophages (CD68), LPS-binding protein receptor (CD14), and LBP (big42). 28 (93%) patients showed moderate to severe periodontitis. The periodontal pathogens in the oral samples of all patients revealed a similar distribution (3-93%). To a lesser extent and with a different distribution, these bacteria DNA were also detected in atrium and myocardium (3-27%). The LBP was detected in higher amount in atrium (0.22±0.16) versus myocardium (0.13±0.13, p=0.001). IHC showed a higher inflammation score in atrial than myocardial tissue as well as for CD14, CD68 and for LBP. Additional, periodontal findings showed a significant correlation to CD14 and CD68. The results provide evidence of the occurrence of oral bacteria DNA at the cardiac tissue, with a different impact on atrial and myocardial tissue inflammation. Influence of periodontal findings was identified, but their relevance is not yet distinct. Therefore further clinical investigations with long term implication are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.
Kwon, Douglas S.; Angin, Mathieu; Hongo, Tomoyuki; Law, Kenneth M.; Johnson, Jessica; Porichis, Filippos; Hart, Meghan G.; Pavlik, David F.; Tighe, Daniel P.; Kavanagh, Daniel G.; Streeck, Hendrik; Addo, Marylyn M.
2012-01-01
T cell dysfunction in the presence of ongoing antigen exposure is a cardinal feature of chronic viral infections with persistent high viremia, including HIV-1. Although interleukin-10 (IL-10) has been implicated as an important mediator of this T cell dysfunction, the regulation of IL-10 production in chronic HIV-1 infection remains poorly understood. We demonstrated that IL-10 is elevated in the plasma of individuals with chronic HIV-1 infection and that blockade of IL-10 signaling results in a restoration of HIV-1-specific CD4 T cell proliferation, gamma interferon (IFN-γ) secretion, and, to a lesser extent, IL-2 production. Whereas IL-10 blockade leads to restoration of IFN-γ secretion by HIV-1-specific CD4 T cells in all categories of subjects investigated, significant enhancement of IL-2 production and improved proliferation of CD4 T helper cells are restricted to viremic individuals. In peripheral blood mononuclear cells (PBMCs), this IL-10 is produced primarily by CD14+ monocytes, but its production is tightly controlled by regulatory T cells (Tregs), which produce little IL-10 directly. When Tregs are depleted from PBMCs of viremic individuals, the effect of the IL-10 signaling blockade is abolished and IL-10 production by monocytes decreases, while the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), increases. The regulation of IL-10 by Tregs appears to be mediated primarily by contact or paracrine-dependent mechanisms which involve IL-27. This work describes a novel mechanism by which regulatory T cells control IL-10 production and contribute to dysfunctional HIV-1-specific CD4 T cell help in chronic HIV-1 infection and provides a unique mechanistic insight into the role of regulatory T cells in immune exhaustion. PMID:22496237
Kawasaki, Yasufumi; Sato, Kazuya; Hayakawa, Hiroko; Takayama, Norihito; Nakano, Hirofumi; Ito, Ryoji; Mashima, Kiyomi; Oh, Iekuni; Minakata, Daisuke; Yamasaki, Ryoko; Morita, Kaoru; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Fujiwara, Shin-Ichiro; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu
2018-04-17
Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4 + and CD8 + T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rg null mice. CD4 + T cells and, to a lesser extent, CD8 + T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4 + T cells also supported the activation and proliferation of CD8 + T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4 + T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4 + T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC) +/+ mice but not in MHC -/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD. Copyright © 2018. Published by Elsevier Inc.
Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells
Janjanin, Sasa; Djouad, Farida; Shanti, Rabie M; Baksh, Dolores; Gollapudi, Kiran; Prgomet, Drago; Rackwitz, Lars; Joshi, Arjun S; Tuan, Rocky S
2008-01-01
Introduction Mesenchymal progenitor cells (MPCs) are multipotent progenitor cells in adult tissues, for example, bone marrow (BM). Current challenges of clinical application of BM-derived MPCs include donor site morbidity and pain as well as low cell yields associated with an age-related decrease in cell number and differentiation potential, underscoring the need to identify alternative sources of MPCs. Recently, MPC sources have diversified; examples include adipose, placenta, umbilicus, trabecular bone, cartilage, and synovial tissue. In the present work, we report the presence of MPCs in human tonsillar tissue. Methods We performed comparative and quantitative analyses of BM-MPCs with a subpopulation of adherent cells isolated from this lymphoid tissue, termed tonsil-derived MPCs (T-MPCs). The expression of surface markers was assessed by fluorescent-activated cell sorting analysis. Differentiation potential of T-MPCs was analyzed histochemically and by reverse transcription-polymerase chain reaction for the expression of lineage-related marker genes. The immunosuppressive properties of MPCs were determined in vitro in mixed lymphocyte reactions. Results Surface epitope analysis revealed that T-MPCs were negative for CD14, CD31, CD34, and CD45 expression and positive for CD29, CD44, CD90, and CD105 expression, a characteristic phenotype of BM-MPCs. Similar to BM-MPCs, T-MPCs could be induced to undergo adipogenic differentiation and, to a lesser extent, osteogenic and chondrogenic differentiation. T-MPCs did not express class II major histocompatibility (MHC) antigens, and in a similar but less pronounced manner compared with BM-MPCs, T-MPCs were immunosuppressive, inhibiting the proliferation of T cells stimulated by allogeneic T cells or by non-specific mitogenic stimuli via an indoleamine 2,3-dioxygenase-dependent mechanism. Conclusion Human palatine T-MPCs represent a new source of progenitor cells, potentially applicable for cell-based therapies. PMID:18662393
Pakseresht, M; Mead, E; Gittelsohn, J; Roache, C; Sharma, S
2010-10-01
The extent to which awareness of chronic disease (CD) diagnosis affects one's healthy food knowledge, self-efficacy and intentions or healthy dietary and physical activity (PA) behaviours remains unexplored among Inuit in Canada. A food frequency questionnaire and an adult impact questionnaire were used in a cross-sectional study to collect self-reported data on daily energy and nutrient intake, PA and the diagnosis of hypertension, diabetes, heart disease and cancer amongst adult Inuit and their family members. Associations between awareness of personal and family CD status and healthy food knowledge, self-efficacy and intentions, percentage of energy consumed from non-nutrient-dense foods and PA were assessed via ordinal logistic regression. Of the 266 participants, those who self-reported CD for both themselves and their relative(s) were more likely to have high healthy food knowledge [odds ratio (OR)=2.45] than those who did not. Reporting hypertension and heart disease amongst only relatives increased the likelihood of high knowledge (OR=5.20) and intentions (OR=5.10) for healthy eating. Heart disease in both participants and their relatives was associated with high levels of PA (OR=12.24). However, there were no associations when only participants (but not their relatives) reported having CD. A joint effect between a high level of education and awareness of CD was positively related to high food knowledge (OR=38.93). An inverse association between awareness of CD and unhealthy eating was not observed. Awareness of a relative having a CD was a more important factor in increasing knowledge and, to a lesser degree, self-efficacy or intentions to eat healthy than participants' awareness of personal CD. However, awareness was not associated with lower non-nutrient-dense food intake. © 2010 The Authors. Journal compilation © 2010 The British Dietetic Association Ltd.
Isajevs, Sergejs; Liepniece-Karele, Inta; Svirina, Darja; Santare, Daiga; Kaidaks, Sandris; Sivins, Armands; Vikmanis, Uldis; Leja, Marcis
2015-12-01
Appropriate biopsy sampling is important for the classification of gastritis, yet the extent of inflammation and atrophy of different regions of the stomach with chronic gastritis have been addressed only in a few studies. The aim of our study was to analyze the inflammatory, atrophic and metaplastic changes in the greater and lesser curvature of the antrum and corpus mucosa. 420 patients undergoing upper endoscopy were enrolled in the study. Four expert gastrointestinal pathologists graded biopsy specimens according to the updated Sydney classification. The obtained results showed that the mononuclear and granulocyte inflammatory cells were more prominent in the corpus lesser curvature compared to the corpus greater curvature (p=0.01 and p=0.0001, respectively). In addition, the extent and degree of atrophy and intestinal metaplasia were more prominent in the corpus lesser compared to the greater curvature (p=0.002 and p=0.0065, respectively). The frequency of distribution of H. pylori did not differ throughout both the corpus and antrum greater and lesser curvature. However, the degree of H. pylori colonization in the corpus was higher in the lesser than in the greater curvature. The interobserver agreement was significantly higher for corpus atrophy compared to antrum atrophy. These findings demonstrated that the more severe atrophic, metaplastic and inflammatory changes were observed in the lesser compared to the greater curvature of the stomach. In routine clinical settings, corpus and antral biopsies should be obtained from both lesser and greater curvature. Analysis of the incisura biopsy is also important.
Inhibitor of endocytosis impairs gene electrotransfer to mouse muscle in vivo.
Markelc, Bostjan; Skvarca, Eva; Dolinsek, Tanja; Kloboves, Veronika Prevodnik; Coer, Andrej; Sersa, Gregor; Cemazar, Maja
2015-06-01
Application of electric pulses (electroporation/electropermeabilization) is an effective method for gene transfer (i.e. gene electrotransfer (GET)) in vitro and in vivo. Currently, the mechanisms by which the DNA enters the cell are not yet fully understood. Experimental evidence is building up that endocytosis is the main mechanism by which the DNA, which is later expressed, enters the cell. Therefore the aim of our study was to elucidate whether inhibitors of endocytosis, methyl-β-cyclodextrin (MβCD), Concanavalin A (ConA) and Dynasore, can impair the transfection efficacy of GET in vitro in B16F1 murine melanoma and in vivo in m. tibialis cranialis in mice. We show that MβCD--general inhibitor of endocytosis--can almost prevent GET of EGFP-N1 plasmid in vitro, that ConA--inhibitor of clathrin mediated endocytosis--also abrogates GET but to a lesser extent, and when using Dynasore--reversible inhibitor of dynamin--there is no effect on GET efficacy, if endocytosis is blocked for only 5 min after GET. Moreover, MβCD also reduced GET efficacy in vivo in m. tibialis cranialis and this effect was long lasting. The results of this study show that endocytosis is probably the main mechanism of entrance of DNA after GET in vitro and also in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.
van Schie, Rob C. A. A.; Wilson, Mark E.
2000-01-01
Two classes of low-affinity receptors for the Fc region of immunoglobulin G (IgG) (FcγR) are constitutively expressed on resting human neutrophils. These receptors, termed FcγRIIa (CD32) and FcγRIIIb (CD16), display biallelic polymorphisms which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. The H131-R131 polymorphism of CD32 influences binding of human IgG2 and, to a lesser extent, human IgG3 to neutrophils. The neutrophil antigen (NA1-NA2) polymorphism of CD16 influences the efficiency of phagocytosis of bacteria opsonized by human IgG1 and IgG3. These polymorphisms may influence host susceptibility to certain infectious and/or autoimmune diseases, prompting interest in the development of facile methods for determination of CD32 and CD16 genotype in various clinical settings. We previously reported that genomic DNA from saliva is a suitable alternative to DNA from blood in PCR-based analyses of CD32 and CD16 polymorphisms. In the present study, we utilized for the first time this salivary DNA-based methodology to define CD32 and CD16 genotypes in 271 Caucasian and 118 African-American subjects and to investigate possible linkage disequilibrium between certain CD32 and CD16 genotypes in these two ethnic groups. H131 and R131 gene frequencies were 0.45 and 0.55, respectively, among Caucasians and 0.59 among African-Americans. NA1 and NA2 gene frequencies were 0.38 and 0.62 among Caucasians and 0.39 and 0.61 among African-Americans. Since FcγRIIa and FcγRIIIb synergize in triggering neutrophils, we also assessed the frequency of different CD32 and CD16 genotype combinations in these two groups. In both groups, the R/R131-NA2/NA2 genotype combination was more common than the H/H131-NA1/NA1 combination (threefold for Caucasians versus sevenfold for African-Americans). Whether individuals with the combined R/R131-NA2/NA2 genotype are at greater risk for development of infectious and/or autoimmune diseases requires further investigation, which can be conveniently performed using DNA from saliva rather than blood. PMID:10882671
Tandy, Susan; Schulin, Rainer; Nowack, Bernd
2006-04-15
The use of chelants to enhance phytoextraction is one method being tested to make phytoextraction efficient enough to be used as a remediation technique for heavy metal pollution in the field. We performed pot experiments with sunflowers in order to investigate the use of the biodegradable chelating agent SS-EDDS for this purpose. We used singly and combined contaminated soils (Cu, Zn) and multimetal contaminated field soils (Cu, Zn, Cd, Pb). EDDS (10 mmol kg(-10 soil) increased soil solution metals greatly for Cu (factor 840-4260) and Pb (factor 100-315), and to a lesser extent for Zn (factor 23-50). It was found that Zn (when present as the sole metal), Cu, and Pb uptake by sunflowers was increased by EDDS, butin multimetal contaminated soil Zn and Cd were not. EDDS was observed in the sunflower roots and shoots at concentrations equal to metal uptake. The different metal uptake in the various soils can be related to a linear relationship between Cu and Zn in soil solution in the presence of EDDS and plant uptake, indicating the great importance of measuring and reporting soil solution metal concentrations in phytoextraction studies.
Anthropogenic metal enrichment of snow and soil in north-eastern European Russia.
Walker, T R; Young, S D; Crittenden, P D; Zhang, H
2003-01-01
Trace metal composition of winter snowpack, snow-melt filter residues and top-soil samples were determined along three transects through industrial towns in the Usa basin, North-East Russia: Inta, Usinsk and Vorkuta. Snow was analysed for Ag, Al, As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr and Zn using ICP-MS (Ca and K by F-AAS for Vorkuta only), pH and acidity/alkalinity. Filter residues were analysed for: Al, Ba, Ca, Cd, Cu, K, Mg, Mn, Ni, Pb, Sr and Zn using F-AAS and GF-AAS; top-soil samples were analysed for Ba, Cu, Mg, Mn, Na, Ni, Pb, Sr, Zn using F-AAS. Results indicate elevated concentrations of elements associated with alkaline combustion ash around the coal mining towns of Vorkuta and Inta. There is little evidence of deposition around the gas and oil town of Usinsk. Atmospheric deposition in the vicinity of Vorkuta, and to a lesser extent Inta, added significantly to the soil contaminant loading as a result of ash fallout. Acid deposition was associated with pristine areas whereas alkaline combustion ash near to emission sources more than compensated for the acidity caused by SO2.
Asahi, Hiroko; Osman, Ahmed; Cook, Rosemary M.; LoVerde, Philip T.; Stadecker, Miguel J.
2000-01-01
In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4+ T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4+ Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62-kDa component was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinase (PEPCK). Based on this sequence, a cDNA clone containing the entire coding region of PEPCK was identified, and the full recombinant Schistosoma mansoni PEPCK (rSm-PEPCK) of 626 amino acids was purified from a prokaryotic expression system. rSm-PEPCK strongly stimulated a specific T-cell hybridoma, 4E6, as well as CD4+ Th cells from SEA-immunized BL/6 mice and from infected BL/6, CBA, and BALB/c mice. In the infected mice, rSm-PEPCK elicited significant gamma interferon production as well as, to a lesser extent, production of interleukin-2 and -5. In BL/6 and BALB/c mice, the CD4+ Th cell response to rSm-PEPCK was greater than that directed against the egg antigen Sm-p40; conversely, CBA mice responded better to Sm-p40 than to Sm-PEPCK. A 12-amino-acid region (residues 398 to 409: DKSKDPKAHPNS) was demonstrated to contain a T-cell epitope; synthetic peptides containing this epitope significantly stimulated specific hybridoma 4E6 and polyclonal CD4+ Th cells. The identification and characterization of immunogenic egg components will contribute to the understanding and possible control of T-cell-mediated schistosomal disease. PMID:10816489
Wang, Yun; Kendall, John; Cavet, Jennifer S.; Giedroc, David P.
2010-01-01
Metal homeostasis and resistance in bacteria is maintained by a panel of metal sensing transcriptional regulators that collectively control transition metal availability and mediate resistance to heavy metal xenobiotics, including AsIII, CdII, PbII and HgII. The ArsR family constitutes a superfamily of metal sensors that appear to conform to the same winged helical, homodimeric fold, that collectively “sense” a wide array of beneficial metal ions and heavy metal pollutants. The genomes of many actinomycetes, including the soil dwelling bacterium Streptomyces coelicolor and the human pathogen Mycobacterium tuberculosis, encode over ten ArsR family regulators, most of unknown function. Here, we present the characterization of a homolog of M. tuberculosis CmtR (CmtRMtb) from S. coelicolor, denoted CmtRSc. We show that CmtRSc, in contrast to CmtRMtb binds two monomer mol equivalents of PbII or CdII to form two pairs of trigonal S3 coordination complexes per dimer. Metal site 1 conforms exactly to the α4C site previously characterized in CmtRMtb while metal site 2 is coordinated by a C-terminal vicinal thiolate pair, Cys110 and Cys111. Biological assays reveal that only CdII and, to a lesser extent, PbII mediate transcriptional derepression in the heterologous host M. smegmatis in a way that requires metal site 1. In contrast, mutagenesis of metal site 2 ligands Cys110 or Cys111 significantly reduces CdII responsiveness, with no detectable effect on PbII sensing. The implications of these findings on the ability to predict metal specificity and function from metal-site “signatures” in the primary structure of ArsR family proteins are discussed. PMID:20586430
Madejon, P.; Murillo, J.M.; Maranon, T.; Espinar, J.L.; Cabrera, F.
2006-01-01
The collapse of a pyrite-mining, tailing dam on 1998 contaminated an area of 4286 ha along the Agrio and Guadiamar river valleys in southern Spain. Over 2700 ha of the Doñana marshes, an important wintering area for wetland European birds, were contaminated. This study reports analyses of the tubers of Scirpus maritimus (an important food for greylag geese, Anser anser) collected in 2000 in the “Entremuros” (spill-affected area) and in nearby unaffected Doñana marshes (control areas). In the spill-affected area mean tuber tissue concentrations of Cd (0.25 mg kg−1) and Zn (61 mg kg−1) were greater than in those tubers from the control area (0.02 mg kg−1 for Cd, and 22 mg kg−1 for Zn); values of Cd and Zn in “Entremuros” (samples collected two years after the mine spill) were much smaller than those reported only a few months after the accident. Trace elements (As, Fe, Mn and Tl, and to a lesser extent Cd and Pb) showed a preferential accumulation in the outer skin of tubers. Surprisingly, concentrations of As and Fe were greater in tubers from some marsh sites not affected by the mine-spill than in tubers from the “Entremuros”. We suggest that relic river channels within the Doñana marshes may be contaminated by trace elements from historic mining activities. An exhaustive study of macrophytes and other plant species in this area is recommended to identify potential risks to wildlife.
Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells
Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.
2007-01-01
Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318
USDA-ARS?s Scientific Manuscript database
Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser...
Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study
Fouad, Hanan; Raziky, Maissa Saeed El; Aziz, Rasha Ahmed Abdel; Sabry, Dina; Aziz, Ghada Mahmoud Abdel; Ewais, Manal; Sayed, Ahmed Reda
2013-01-01
AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients. PMID:24282359
Jeannin, P; Delneste, Y; Lecoanet-Henchoz, S; Gretener, D; Bonnefoy, J Y
1998-02-15
Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone marrow stroma cells and follicular dendritic cells (FDCs) located in primary lymphoid follicles and germinal centers. In this study, we have evaluated the role of IL-7 on human Ig class switching. IL-7 was added to peripheral blood mononuclear cells (PBMCs) or tonsillar B cells in the absence or presence of IL-4 and/or anti-CD40 monoclonal antibody (MoAb). Alone, IL-7 did not affect Ig production by PBMCs or by anti-CD40 MoAb-stimulated B cells. Rather, IL-7 potentiated IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3 production was also enhanced but to a lesser extent, whereas the production of the other isotypes was unaltered. The activity of IL-2, IL-9, or IL-15, which share usage of the common gamma chain for signaling, was also assessed. IL-9, like IL-7, potentiated mainly IgE and IgG4 production by IL-4-stimulated PBMCs. IL-15, in contrast, was ineffective, whereas IL-2 enhanced the production of all isotypes. More precisely, IL-7 potentiation of IgE and IgG4 production required the presence of T cells and was accompanied by an increase of the expression of two soluble molecules favoring preferentially IgE and IgG4 synthesis: CD23 (sCD23) and IL-9. Moreover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibited the increase of IgE synthesis induced by IL-7. Thus, IL-7 produced locally in the germinal centers by FDCs may interact with T cells and potentiate human IgE and IgG4 switching by favoring IL-9 and sCD23 production.
Petenzi, Michele; Verga, Daniela; Largy, Eric; Hamon, Florian; Doria, Filippo; Teulade-Fichou, Marie-Paule; Guédin, Aurore; Mergny, Jean-Louis; Mella, Mariella; Freccero, Mauro
2012-11-05
We report herein a solvent-free and microwaved-assisted synthesis of several water soluble acyclic pentaheteroaryls containing 1,2,4-oxadiazole moieties (1-7). Their binding interactions with DNA quadruplex structures were thoroughly investigated by FRET melting, fluorescent intercalator displacement assay (G4-FID) and CD spectroscopy. Among the G-quadruplexes considered, attention was focused on telomeric repeats together with the proto-oncogenic c-kit sequences and the c-myc oncogene promoter. Compound 1, and to a lesser extent 2 and 5, preferentially stabilise an antiparallel structure of the telomeric DNA motif, and exhibit an opposite binding behaviour to structurally related polyoxazole (TOxaPy), and do not bind duplex DNA. The efficiency and selectivity of the binding process was remarkably controlled by the structure of the solubilising moieties. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
γδ T cell homeostasis is established in competition with αβ T cells and NK cells
French, Jena D.; Roark, Christina L.; Born, Willi K.; O'Brien, Rebecca L.
2005-01-01
γδ T cells are a diverse population of lymphocytes that play an important role in immune regulation. The size of the γδ T cell pool is tightly regulated, comprising only 1-10% of total lymphoid T cells in mice and humans. We examined the homeostatic regulation of γδ T cells using a model of lymphopenia-induced homeostatic expansion. We found that IL-15 and, to a lesser extent, IL-7 play an important role in lymphoid γδ T cell homeostasis. Moreover, γδ T cell homeostatic expansion was limited not only by γδ T cells themselves but also by natural killer cells and αβ T cells. Our results suggest that CD8+ αβ T cells are the most potent inhibitors of γδ T cell homeostasis and exert their effect by competing for IL-15. PMID:16203967
HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+ T Cell Responses
Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Seaman, Michael S.; Kaufmann, Daniel E.; Walker, Bruce D.
2015-01-01
ABSTRACT Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells and, to a lesser extent, gp41-specific CD4+ T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies. IMPORTANCE One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+ T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+ T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+ T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection. PMID:26656715
Tsiountsioura, M; Wong, J E; Upton, J; McIntyre, K; Dimakou, D; Buchanan, E; Cardigan, T; Flynn, D; Bishop, J; Russell, R K; Barclay, A; McGrogan, P; Edwards, C; Gerasimidis, K
2014-06-01
In the era of modern multidisciplinary clinical management, very little is known about the prevalence and presentation of malnutrition in children with gastrointestinal disorders (GastroD) particularly employing composite, global measures of nutritional status. Anthropometry, body composition, dietary intake, eating habits and grip strength were assessed with bedside methods in 168 patients from outpatient gastroenterology clinics (n, median (IQR) years; Crohn's disease (CD): n=53, 14.2 (11.6:15.4); ulcerative colitis (UC): n=27, 12.2 (10.7:14.2); coeliac disease: n=31, 9.3 (7.5:13.6); other GastroD: n=57, 9.8 (7.2:13.8)) and compared with 62 contemporary healthy controls (n, median (IQR): 9.8 (6.9:13.8)) and the results of the recent UK, National Diet and Nutritional Survey (NDNS). Children with CD had lower BMI z-scores than controls (median (IQR): -0.3 (-0.9:0.4) vs 0.3 (-0.6:1.4); P=0.02) but only 2% were classified as thin (BMI z-score <-2 s.d.). The prevalence of obesity in children with UC was 19%, 6% in CD, 11% in children with other GastroD and 15% in controls. No difference was found in grip strength measurement between groups. Except for CD children, the proportion of patients with suboptimal micronutrient intake was similar to that of controls and the cohort of children from the latest NDNS. A higher proportion of children with CD had suboptimal intake for riboflavin, vitamin B6 and calcium and consumed significantly more meat products, juices (including carbonated drinks), spreads/jams and crisps and savoury snacks and significantly fewer portions of dairy, fish, fruits and vegetables compared with healthy controls. GastroD affect children's body composition, growth, strength, dietary intake and eating habits, particularly CD, but to a lesser extent than expected.
McPherson, Nicole O.; Bakos, Hassan W.; Owens, Julie A.; Setchell, Brian P.; Lane, Michelle
2013-01-01
Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health. PMID:23977045
Montrucchio, Giuseppe; Bosco, Ornella; Del Sorbo, Lorenzo; Fascio Pecetto, Paolo; Lupia, Enrico; Goffi, Alberto; Omedè, Paola; Emanuelli, Giorgio; Camussi, Giovanni
2003-11-01
Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS. LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators. In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.
de Bruyn, Magali; Arijs, Ingrid; De Hertogh, Gert; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Séverine; Opdenakker, Ghislain
2015-12-01
Although costly and uncomfortable for the patient, the current standard to assess mucosal healing in Crohn's disease [CD] patients is endoscopy. The aim of this study was to evaluate NGAL-MMP-9 as surrogate marker for mucosal healing in CD patients. Serum NGAL-MMP-9 levels were determined with sandwich enzyme-linked immunosorbent assay before and up to 5 years after first infliximab infusion in 108 active CD patients [median age at first infliximab 36 years, 57% female] and 43 healthy controls [HC, median age 27 years, 60% female]. Serum samples were matched to the time of endoscopy and complete endoscopic healing was defined as absence of ulcerations. Histological healing was defined as absence of epithelial damage [D'Haens score]. At baseline, median [interquartile range] NGAL-MMP-9 levels were significantly higher in active CD patients vs HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p < 0.001). After treatment, NGAL-MMP-9 levels significantly decreased in completely healed CD patients [n = 38] (84.5 [36.7-138.4] to 23.4 [7.4-42.5] ng/ml; p < 0.001) and--to a lesser extent--in non-healed CD patients [n = 36] (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p = 0.001). Receiver operating characteristic analysis defined a NGAL-MMP-9 cut-off level of 45 ng/ml corresponding to complete endoscopic healing (area under the curve [AUC] = 0.79, 82% sensitivity, 65% specificity) and histological healing [AUC = 0.72, 79% sensitivity, 53% specificity]. At baseline, C-reactive protein [CRP] was not elevated in 33% of active CD patients, whereas 53% of these patients did have elevated NGAL-MMP-9 levels. In the search for surrogate markers to assess mucosal healing in inflammatory bowel disease, NGAL-MMP-9 supplements and outperforms CRP in both ulcerative colitis and CD patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Evidence for unmyelinated C fibres and inflammatory cells in human varicose saphenous vein
Vital, Anne; Carles, Dominique; Serise, Jean-Michel; Boisseau, Michel René
2010-01-01
The physiopathology of venous symptoms, such as pain, leg heaviness or swelling sensations, in chronic venous disease (CVD) remains unclear. Localized release of proinflammatory mediators appears to play a key role but the presence of nociceptors sensitive to inflammatory mediators, such as unmyelinated C fibres, needs to be demonstrated. The present study included 10 patients with documented CVD who underwent surgery for saphenectomy. For each patient, five segments of the great saphenous vein were immunostained with anti-S100 protein and anti-CD45 to identify nerve fibres and inflammatory cells, respectively. Light microscopy was completed by electron microscopy. In all patients, S100 immunopositive nerve fibres and CD45 immunopositive cells were observed. Under an electron microscope, advanced signs of wall remodelling were systematically observed. The density of nerve fibres was low and variable from one sample to another. Unmyelinated C fibres were mainly located in the external part of the media and to a lesser extent in the internal part of the adventitia. Inflammatory cells, mainly histiocytes, were scattered in the media. Mast cells were observed in three patients. In conclusion, unmyelinated C fibres and inflammatory cells are present in the varicose saphenous vein wall. Their linked roles in symptoms of CVD should be further explored. PMID:22477593
NASA Astrophysics Data System (ADS)
Kelley, Katherine A.; Kingsley, Richard; Schilling, Jean-Guy
2013-01-01
The global mid-ocean ridge system is peppered with localities where mantle plumes impinge on oceanic spreading centers. Here, we present new, high resolution and high precision data for 40 trace elements in 573 samples of variably plume-influenced mid-ocean ridge basalts from the Mid-Atlantic ridge, the Easter Microplate and Salas y Gomez seamounts, the Galápagos spreading center, and the Gulf of Aden, in addition to previously unpublished major element and isotopic data for these regions. Included in the data set are the unconventional trace elements Mo, Cd, Sn, Sb, W, and Tl, which are not commonly reported by most geochemical studies. We show variations in the ratios Mo/Ce, Cd/Dy, Sn/Sm, Sb/Ce, W/U, and Rb/Tl, which are expected not to fractionate significantly during melting or crystallization, as a function of proximity to plume-related features on these ridges. The Cd/Dy and Sn/Sm ratios show little variation with plume proximity, although higher Cd/Dy may signal increases in the role of garnet in the mantle source beneath some plumes. Globally, the Rb/Tl ratio closely approximates the La/SmN ratio, and thus provides a sensitive tracer of enriched mantle domains. The W/U ratio is not elevated at plume centers, but we find significant enrichments in W/U, and to a lesser extent the Mo/Ce and Sb/Ce ratios, at mid-ocean ridges proximal to plumes. Such enrichments may provide evidence of far-field entrainment of lower mantle material that has interacted with the core by deeply-rooted, upwelling mantle plumes.
Circulating Angiogenic Cells can be Derived from Cryopreserved Peripheral Blood Mononuclear Cells
Sofrenovic, Tanja; McEwan, Kimberly; Crowe, Suzanne; Marier, Jenelle; Davies, Robbie; Suuronen, Erik J.; Kuraitis, Drew
2012-01-01
Background Cell transplantation for regenerative medicine has become an appealing therapeutic method; however, stem and progenitor cells are not always freshly available. Cryopreservation offers a way to freeze cells as they are generated, for storage and transport until required for therapy. This study was performed to assess the feasibility of cryopreserving peripheral blood mononuclear cells (PBMCs) for the subsequent in vitro generation of their derived therapeutic population, circulating angiogenic cells (CACs). Methods PBMCs were isolated from healthy human donors. Freshly isolated cells were either analyzed immediately or cryopreserved in media containing 6% plasma serum and 5% dimethyl sulfoxide. PBMCs were thawed after being frozen for 1 (early thaw) or 28 (late thaw) days and analyzed, or cultured for 4 days to generate CACs. Analysis of the cells consisted of flow cytometry for viability and phenotype, as well as functional assays for their adhesion and migration potential, cytokine secretion, and in vivo angiogenic potential. Results The viability of PBMCs and CACs as well as their adhesion and migration properties did not differ greatly after cryopreservation. Phenotypic changes did occur in PBMCs and to a lesser extent in CACs after freezing; however the potent CD34+VEGFR2+CD133+ population remained unaffected. The derived CACs, while exhibiting changes in inflammatory cytokine secretion, showed no changes in the secretion of important regenerative and chemotactic cytokines, nor in their ability to restore perfusion in ischemic muscle. Conclusion Overall, it appears that changes do occur in cryopreserved PBMCs and their generated CACs; however, the CD34+VEGFR2+CD133+ progenitor population, the secretion of pro-vasculogenic factors, and the in vivo angiogenic potential of CACs remain unaffected by cryopreservation. PMID:23133548
del Rio, Maria-Luisa; Fernandez-Renedo, Carlos; Scheu, Stefanie; Pfeffer, Klaus; Shintani, Yasushi; Kronenberg, Mitchell; Chaloin, Olivier; Schneider, Pascal; Rodriguez-Barbosa, Jose-Ignacio
2016-01-01
Background TNF/TNFR superfamily members conform a group of molecular interaction pathways of essential relevance during the process of T cell activation and differentiation towards effector cells and particularly for the maintenance phase of the immune response. Specific blockade of these interacting pathways, such as CD40/CD40L, contributes to modulate the deleterious outcome of allogeneic immune responses. We postulated that antagonizing the interaction of LIGHT expression on activated T cells with its receptors, HVEM and LTβR may decrease T cell-mediated allogeneic responses. Methods A flow cytometry competition assay was designed to identify anti-LIGHT monoclonal antibodies capable to prevent the interaction of mouse LIGHT with its receptors expressed on transfected cells. An antibody with the desired specificity was evaluated in a short-term in vivo allogeneic cytotoxic assay and tested for its ability to detect endogenous mouse LIGHT. Results We provide evidence for the first time that in mice, as previously described in humans, LIGHT protein is rapidly and transiently expressed after T cell activation, and this expression was stronger on CD8 T cells than on CD4 T cells. Two anti-LIGHT antibodies prevented interactions of mouse LIGHT with its two known receptors HVEM and LTβR. In vivo administration of anti-LIGHT antibody (clone 10F12) ameliorated host anti-donor short-term cytotoxic response in WT B6 mice, although to a lesser extent than that observed in LIGHT-deficient mice. Conclusions The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation. PMID:25226173
B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS.
Pedersen, Gabriel K; Àdori, Monika; Khoenkhoen, Sharesta; Dosenovic, Pia; Beutler, Bruce; Karlsson Hedestam, Gunilla B
2014-09-30
B-1 cells mediate early protection against infection by responding to T cell-independent (TI) antigens found on the surface of various pathogens. Mice with impaired expression of the atypical IκB protein IκBNS have markedly reduced frequencies of B-1 cells. We used a mouse strain with dysfunctional IκBNS derived from an N-ethyl-N-nitrosourea (ENU) screen, named bumble, to investigate the point in the development of B-1 cells where IκBNS is required. The presence of wild-type (wt) peritoneal cells in mixed wt/bumble chimeras did not rescue the development of bumble B-1 cells, but wt peritoneal cells transferred to bumble mice restored natural IgM levels and response to TI antigens. The bumble and wt mice displayed similar levels of fetal liver B-1 progenitors and splenic neonatal transitional B (TrB) cells, both of which were previously shown to give rise to B-1 cells. Interestingly, we found that a subset of wt neonatal TrB cells expressed common B-1a markers (TrB-1a) and that this cell population was absent in the bumble neonatal spleen. Sorted TrB-1a (CD93(+)IgM(+)CD5(+)) cells exclusively generated B-1a cells when adoptively transferred, whereas sorted CD93(+)IgM(+)CD5(-) cells gave rise to B-2 cells and, to a lesser extent, B-1b and B-1a cells. This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS.
Stankevičiūtė, Milda; Sauliutė, Gintarė; Svecevičius, Gintaras; Kazlauskienė, Nijolė; Baršienė, Janina
2017-10-01
Health impact of metal mixture at environment realistic concentrations are difficult to predict especially for long-term effects where cause-and-effect relationships may not be directly obvious. This study was aimed to evaluate metal mixture (Zn-0.1, Cu-0.01, Ni-0.01, Cr-0.01, Pb-0.005 and Cd-0.005 mg/L, respectively for 1, 2, 4, 7, 14 and 28 days at concentrations accepted for the inland waters in EU) genotoxicity (micronuclei, nuclear buds, nuclear buds on filament), cytotoxicity (8-shaped nuclei, fragmented-apoptotic erythrocytes), bioaccumulation, steady-state and the reference level of geno-cytotoxicity in hatchery-reared Atlantic salmon tissues. Metals accumulated mostly in gills and kidneys, to the lesser extent in the muscle. Uptake of metals from an entire mixture in the fish for 14 days is sufficient to reach steady-state Cr, Pb concentrations in all tissues; Zn, Cu-in kidneys and muscle, Ni-in liver, kidneys, muscle and Cd-in muscle. Treatment with metal mixture significantly increased summed genotoxicity levels at 7 days of exposure in peripheral blood and liver erythrocytes, at 14 days of exposure in gills and kidney erythrocytes. Significant elevation of cytotoxicity was detected after 2 and 14 days of exposure in gills erythrocytes and after 28 days-in peripheral blood erythrocytes. The amount of Cu, Cr, Pb and Cd accumulated in tissues was dependent upon duration of exposure; nuclear buds, 8-shaped nuclei frequencies also were dependent upon duration of exposure. This study indicates that metals at low levels when existing in mixture causes significant geno-cytotoxicity responses and metals bioaccumulation in salmon.
Trace elements in lesser scaup (Aythya affinis) from the Mississippi flyway
Custer, Christine M.; Custer, T.W.; Anteau, M.J.; Afton, A.D.; Wooten, D.E.
2003-01-01
Previous research reported that concentrations of selenium in the livers of 88a??95% of lesser scaup from locations in Lake Erie, Lake St. Clair, and Lake Michigan, USA were either elevated (10a??33 A?g/g dry weight [dw]) or in the potentially harmful range (>33 A?g/g dw). In order to determine the geographic extent of these high selenium concentrations, we collected lesser scaup in Louisiana, Arkansas, Illinois, Minnesota, Wisconsin, and Manitoba and analyzed the livers for 19 trace elements. We found that all trace element concentrations, except for selenium, generally were low. Arsenic, which usually is not detected in liver samples, was detected in Louisiana and may be related to past agricultural usages. Chromium, which also is not usually detected, was only present in lesser scaup from Arkansas and may be related to fertilizer applications. Cadmium and mercury concentrations did not differ among locations and concentrations were low. Selenium concentrations in Arkansas (geometric mean=4.2 A?g/g dw) were significantly lower than those in Louisiana (10.7 A?g/g dw), Illinois (10.5 A?g/g dw), and Minnesota (8.0 A?g/gdw); concentrations in Wisconsin and Manitoba were intermediate (6.6 and 6.5 A?g/g dw). About 25% of lesser scaup livers contained elevated selenium concentrations; however, none were in the harmful range. We concluded that selenium concentrations in lesser scaup in the Mississippi Flyway are elevated in some individuals, but not to the extent that has been documented in the industrial portions of the Great Lakes.
Genetic and environmental risk factors in adolescent substance use.
Silberg, Judy; Rutter, Michael; D'Onofrio, Brian; Eaves, Lindon
2003-07-01
The present study was undertaken with the goal of understanding the causes of association between substance use and both conduct disturbance (CD) and depression in adolescent boys and girls. Multivariate genetic structural equation models were fitted to multi-informant, multi-wave, longitudinal data collected in extensive home interviews with parents and children with respect to 307 MZ male, 392 MZ female, 185 DZ male, and 187 DZ female, same-sex twin pairs aged 12-17 years from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Although conduct disturbance and depression were moderately associated with substance use, the pattern of genetic and environmental risk differed for males and females and across the two disorders. Genetic factors were predominant in girls' substance use whereas boys' use was mediated primarily by shared environmental factors reflecting family dysfunction and deviant peers. The patterns of correlations across the two waves of the study were consistent with conduct disturbance leading to substance use in both males and females, but depression leading to smoking, drug use and, to a lesser extent, alcohol use in girls. The comorbidity between substance use and depression, and between substance use and conduct disturbance in childhood/adolescence, probably reflects rather different mediating mechanisms--as well as a different time frame, with conduct disturbance preceding substance use but depression following it. In both, the co-occurrence partially reflected a shared liability but, in girls, genetic influences played an important role in the comorbidity involving depression, whereas in both sexes (but especially in boys) environmental factors played a substantial role. The extent to which these differences reflect genuine differences in the causal mechanisms underlying substance use and CD/depression in boys and girls revealed in the present analysis awaits replication from studies of other general population samples.
Moncaleano-Niño, Angela M; Barrios-Latorre, Sergio A; Poloche-Hernández, Javier F; Becquet, Vanessa; Huet, Valérie; Villamil, Luisa; Thomas-Guyon, Hélène; Ahrens, Michael J; Luna-Acosta, Andrea
2017-04-01
Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5-5.0cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations≥100μg/L showed a significant increase, from 8.0 to 14.8μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96h of exposure to 1000μg/L Cd, were significantly lower (0.04mg P/g gonad) compared to control oysters (0.68mg P/g gonad), suggestive of an anti-estrogenic effect of Cd at high concentrations, whereas no significant changes in vitellogenin concentrations were observed at intermediate Cd exposure concentrations. This study confirms acute responses of metallothionein and vitellogenin concentrations in tissues of Saccostrea sp. exposed to high concentrations of cadmium (Cd≥100μg/L, 96h). The present results are first step towards validating the use of these two proteins as biomarkers of metal exposure in this species. Copyright © 2017 Elsevier B.V. All rights reserved.
Peachey, C J; Sinnett, D; Wilkinson, M; Morgan, G W; Freer-Smith, P H; Hutchings, T R
2009-01-01
In urban areas, a highly variable mixture of pollutants is deposited as particulate matter. The concentration and bioavailability of individual pollutants within particles need to be characterised to ascertain the risks to ecological receptors. This study, carried out at two urban parks, measured the deposition and water-solubility of metals to four species common to UK urban areas. Foliar Cd, Cr, Cu, Fe, Ni, Pb and Zn concentrations were elevated in at least one species compared with those from a rural control site. Concentrations were, however, only affected by distance to road in nettle and, to a lesser extent, birch leaves. Greater concentrations of metal were observed in these species compared to cypress and maple possibly due to differences in plant morphology and leaf surfaces. Solubility appeared to be linked to the size fraction and, therefore, origin of the metal with those present predominantly in the coarse fraction exhibiting low solubility.
Fallah Shorshani, Masoud; Bonhomme, Céline; Petrucci, Guido; André, Michel; Seigneur, Christian
2014-04-01
Methods for simulating air pollution due to road traffic and the associated effects on stormwater runoff quality in an urban environment are examined with particular emphasis on the integration of the various simulation models into a consistent modelling chain. To that end, the models for traffic, pollutant emissions, atmospheric dispersion and deposition, and stormwater contamination are reviewed. The present study focuses on the implementation of a modelling chain for an actual urban case study, which is the contamination of water runoff by cadmium (Cd), lead (Pb), and zinc (Zn) in the Grigny urban catchment near Paris, France. First, traffic emissions are calculated with traffic inputs using the COPERT4 methodology. Next, the atmospheric dispersion of pollutants is simulated with the Polyphemus line source model and pollutant deposition fluxes in different subcatchment areas are calculated. Finally, the SWMM water quantity and quality model is used to estimate the concentrations of pollutants in stormwater runoff. The simulation results are compared to mass flow rates and concentrations of Cd, Pb and Zn measured at the catchment outlet. The contribution of local traffic to stormwater contamination is estimated to be significant for Pb and, to a lesser extent, for Zn and Cd; however, Pb is most likely overestimated due to outdated emissions factors. The results demonstrate the importance of treating distributed traffic emissions from major roadways explicitly since the impact of these sources on concentrations in the catchment outlet is underestimated when those traffic emissions are spatially averaged over the catchment area.
Pavlaki, Maria D; Morgado, Rui G; van Gestel, Cornelis A M; Calado, Ricardo; Soares, Amadeu M V M; Loureiro, Susana
2017-11-01
mMarine and estuarine ecosystems are highly productive areas that often act as a final sink for several pollutants, such as cadmium. Environmental conditions in these habitats can affect metal speciation, as well as its uptake and depuration by living organisms. The aim of this study was to assess cadmium uptake and depuration rates in the euryhaline calanoid copepod Acartia tonsa under different pH, salinity and temperature conditions. Cadmium speciation did not vary with changing pH or temperature, but varied with salinity. Free Cd 2+ ion activity increased with decreasing salinities resulting in increased cadmium concentrations in A. tonsa. However, uptake rate, derived using free Cd 2+ ion activity, showed no significant differences at different salinities indicating a simultaneous combined effect of Cd 2+ speciation and metabolic rates for osmoregulation. Cadmium concentration in A. tonsa and uptake rate increased with increasing pH, showing a peak at the intermediate pH of 7.5, while depuration rate fluctuated, thus suggesting that both parameters are mediated by metabolic processes (to maintain homeostasis at pH levels lower than normal) and ion competition at membrane binding sites. Cadmium concentration in A. tonsa, uptake and depuration rates increased with increasing temperature, a trend that can be attributed to an increase in metabolic energy demand at higher temperatures. The present study shows that cadmium uptake and depuration rates in the marine copepod A. tonsa is mostly affected by biological processes, mainly driven by metabolic mechanisms, and to a lesser extent by metal speciation in the exposure medium. Copyright © 2017 Elsevier Inc. All rights reserved.
Nakahara, Mami; Nagayama, Yuji; Ichikawa, Tatsuki; Yu, Liping; Eisenbarth, George S; Abiru, Norio
2011-09-01
The nonobese diabetic (NOD) mouse spontaneously develops several autoimmune diseases, including type 1 diabetes and to a lesser extent thyroiditis and sialitis. Imbalance between effector T cells (Teffs) and regulatory T cells (Tregs) has recently been proposed as a mechanism for the disease pathogenesis in NOD mice, but previous studies have shown the various outcomes by different timing and methods of Treg-depletion. This study was, therefore, designed to compare the consequences of Treg-depletion by the same method (anti-CD25 antibody) on the spectrum of organ-specific autoimmune diseases in NOD mice of different ages. Treg-depletion by anti-CD25 antibody at 10 days of age accelerated development of all three diseases we examined (insulitis/diabetes, thyroiditis, and sialitis); Treg-depletion at 4 weeks of age accelerated only diabetes but not thyroiditis or sialitis; and Treg-depletion at 12 weeks of age hastened only development of thyroiditis and exhibited little influence on diabetes or sialitis. Increased levels of insulin autoantibodies (IAA) were, however, observed in mice depleted of Tregs at 10 days of age, not in those at 4 weeks. Thus, the consequences of Treg-depletion on the spectrum of organ-specific autoimmune diseases depend on the timing of anti-CD25 antibody injection in NOD mice. Aging gradually tips balance between Teffs and Tregs toward Teff-dominance for diabetes, but this balance for thyroiditis and sialitis likely alters more intricately. Our data also suggest that the levels of IAA are not necessarily correlated with diabetes development.
USDA-ARS?s Scientific Manuscript database
There is a need to determine the nature and extent of residual reservoirs of Salmonella which contribute to perpetual contamination within poultry flocks. The dispersal of Salmonella between birds, litter, and beetles has been established, but the extent that these act as critical components in the...
Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C
2008-10-23
Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.
Guilmot, Aline; Bosse, Julie; Carlier, Yves; Truyens, Carine
2013-01-01
We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8+ T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56bright NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells), while CD56dim NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates. PMID:23819002
Tsujimura, A; Shida, K; Kitamura, M; Nomura, M; Takeda, J; Tanaka, H; Matsumoto, M; Matsumiya, K; Okuyama, A; Nishimune, Y; Okabe, M; Seya, T
1998-01-01
Human membrane cofactor protein (MCP, CD46) has been suggested, although no convincing evidence has been proposed, to be a fertilization-associated protein, in addition to its primary functions as a complement regulator and a measles virus receptor. We have cloned a cDNA encoding the murine homologue of MCP. This cDNA showed 45% identity in deduced protein sequence and 62% identity in nucleotide sequence with human MCP. Its ectodomains were four short consensus repeats and a serine/threonine-rich domain, and it appeared to be a type 1 membrane protein with a 23-amino acid transmembrane domain and a short cytoplasmic tail. The protein expressed on Chinese hamster ovary cell transfectants was 47 kDa on SDS/PAGE immunoblotting, approximately 6 kDa larger than the murine testis MCP. It served as a cofactor for factor I-mediated inactivation of the complement protein C3b in a homologous system and, to a lesser extent, in a human system. Strikingly, the major message of murine MCP was 1.5 kb and was expressed predominantly in the testis. It was not detected in mice defective in spermatogenesis or with immature germ cells (until 23 days old). Thus, murine MCP may be a sperm-dominant protein the message of which is expressed selectively in spermatids during germ-cell differentiation. PMID:9461505
[The satisfaction of personal needs in patients with pulmonary tuberculosis].
Sukhova, E V
2005-01-01
The founder of humanistic psychology A. Maslow divided the needs of a personality into several levels--from the lowest to the highest ones. Higher-leveled needs rise when the lower-leveled needs are satisfied. A great deal of factors affect the origination and satisfaction of needs, but they are always interrelated with social values. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis has not been studied. A special questionnaire has been drawn up to study the extent to which personality needs are met. Its suitability has been determined, by using a group of patients with bronchial asthma. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis was studied in 178 patients with infiltrative pulmonary tuberculosis and 253 patients with fibrocavernous pulmonary tuberculosis. The results have shown that the extent to which personality needs are satisfied in patients with tuberculosis is lower than that in apparently healthy individuals of the same social status. In females with infiltrative pulmonary tuberculosis, the needs for safety are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, and self-realization needs is decreased. In males with infiltrative pulmonary tuberculosis, the physiological, noetic, and self-realization needs are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, group decision-making, noetic and self-realization needs is decreased.
Mitrofanova, Lubov B; Orshanskaya, Victoria; Ho, Siew Yen; Platonov, Pyotr G
2016-12-01
Chronic inflammation in the atrial myocardium was shown to play an important role in the development of atrial fibrosis in patients with atrial fibrillation (AF). However, it is not clear to what extent atrial inflammatory reaction associated with AF extends on the ventricular myocardium. Our aim was to assess the extent of fibrosis and lymphomononuclear infiltration in human ventricular myocardium and explore its association with AF. Medical records from consecutive autopsies were checked for presence of AF. Heart specimens from 30 patients died from cardiovascular causes (64 ± 12 years, 17 men) were collected in three equal groups: no AF, paroxysmal AF, and permanent AF. Tissue samples were taken from the Bachmann's bundle, crista terminalis, posterior left atrium, left ventricle and right ventricle free walls and stained with Masson's trichrome for analysis of fibrosis extent. Immunohistochemistry was performed using antibodies against CD3- and CD45-antigens and quantified as number of antigen-positive cells per 1 mm 2 . Fibrosis extent, CD3+ and CD45+ cell counts were elevated in AF patients at all sites (P < 0.001 for all). Fibrosis extent demonstrated correlation with both CD3+ and CD45+ cell counts in the right (r = 0.781, P < 0.001 for CD45+ and r = 0.720, P < 0.001 for CD3+) and the left (r = 0.515, P = 0.004 for CD45+ and r = 0.573, P = 0.001 for CD3+) ventricles. Neither fibrosis nor inflammatory cell count showed association with either age or comorbidities. Histological signs of chronic inflammation affecting ventricular myocardium are strongly associated with AF and demonstrate significant correlation with fibrosis extent that cannot be explained by cardiovascular comorbidities otherwise. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.
Prenatal cadmium exposure alters postnatal immune cell development and function
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal
2012-06-01
Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspringmore » were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific. -- Highlights: ► Prenatal exposure to Cd causes no thymocyte phenotype changes in the offspring ► Analysis of the splenocyte phenotype demonstrates a macrophage-specific effect only in male offspring ► The cytokine profiles suggest an effect on peripheral Th1 cells in female and to a lesser degree in male offspring ► There was a marked increase in serum anti-streptococcal antibody levels after immunization in both sexes ► There was a marked decrease in the numbers of splenic CD8{sup +}CD223{sup +} cells in both sexes.« less
Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza
2017-01-01
Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.
Zeng, Huawei; Taussig, David P.; Cheng, Wen-Hsing; Johnson, LuAnn K.; Hakkak, Reza
2017-01-01
Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells. PMID:28045428
To What Extent Do Gestalt Grouping Principles Influence Tactile Perception?
ERIC Educational Resources Information Center
Gallace, Alberto; Spence, Charles
2011-01-01
Since their formulation by the Gestalt movement more than a century ago, the principles of perceptual grouping have primarily been investigated in the visual modality and, to a lesser extent, in the auditory modality. The present review addresses the question of whether the same grouping principles also affect the perception of tactile stimuli.…
ERIC Educational Resources Information Center
Boden, Joseph M.; Fergusson, David M.; Horwood, L. John
2010-01-01
Objective: To examine the social, family background, and individual antecedents of conduct disorder (CD) and oppositional defiant disorder (ODD), the extent to which CD and ODD symptoms were predicted by common environmental risk factors, and the extent to which the antecedents of CD and ODD accounted for the comorbidity between the two disorders.…
Gandois, L; Nicolas, M; VanderHeijden, G; Probst, A
2010-11-01
The trace metal (TM: Cd, Cu, Ni, Pb and Zn) budget (stocks and annual fluxes) was evaluated in a forest stand (silver fir, Abies alba Miller) in north-eastern France. Trace metal concentrations were measured in different tree compartments in order to assess TM partitioning and dynamics in the trees. Inputs included bulk deposition, estimated dry deposition and weathering. Outputs were leaching and biomass exportation. Atmospheric deposition was the main input flux. The estimated dry deposition accounted for about 40% of the total trace metal deposition. The relative importance of leaching (estimated by a lumped parameter water balance model, BILJOU) and net biomass uptake (harvesting) for ecosystem exportation depended on the element. Trace metal distribution between tree compartments (stem wood and bark, branches and needles) indicated that Pb was mainly stored in the stem, whereas Zn and Ni, and to a lesser extent Cd and Cu, were translocated to aerial parts of the trees and cycled in the ecosystem. For Zn and Ni, leaching was the main output flux (>95% of the total output) and the plot budget (input-output) was negative, whereas for Pb the biomass net exportation represented 60% of the outputs and the budget was balanced. Cadmium and Cu had intermediate behaviours, with 18% and 30% of the total output relative to biomass exportation, respectively, and the budgets were negative. The net uptake by biomass was particularly important for Pb budgets, less so for Cd and Cu and not very important for Zn and Ni in such forest stands. Copyright © 2010 Elsevier B.V. All rights reserved.
Hovorka, Miloš; Száková, Jiřina; García-Sánchez, Mercedes; Acebal, Mercedes Blanc; García-Romera, Inmaculada; Tlustoš, Pavel
2016-11-01
Olive oil production is one of the most relevant agroindustrial activities in the Mediterranean region and generates a huge amount of both solid and semi-solid wastes, the uncontrolled disposal of which might lead to serious environmental problems. Due to its organic matter and mineral nutrient content, the waste material can be applied to agricultural soil as a fertilizer. However, due to its high organic matter content, dry olive residue (DOR), commonly called "alperujo," has the potential to immobilize risk elements in contaminated soils. The main objective of this study was to assess the possible effect of DOR on sorption of risk elements such as cadmium (Cd), lead (Pb), and zinc (Zn) in the soil. A set of batch sorption experiments were carried out to assess the ability of DOR to adsorb Cd, Pb, and Zn where the effect of the preceding biotransformation of DOR by four species of fungi: Penicillium chrysogenum, Coriolopsis floccosa, Bjerkhandera adusta, and Chondrostereum purpureum was compared. The Freundlich and Langmuir sorption isotherms were calculated to assess the sorption characteristics of both transformed and non-transformed DOR. The results showed good potential sorption capacity of DOR, especially for Pb and to a lesser extent for Cd and Zn. Better sorption characteristics were reported for the biotransformed DOR samples, which are expected to show higher humification of the organic matter. However, the desorption experiments showed weakness and instability of the DOR-bound elements, especially in the case of Zn. Thus, future research should aim to verify the DOR sorption pattern in contaminated soil as well as the potential stabilization of the DOR element bounds where the increase of the pH levels of the DOR samples needs to be taken into account.
Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y
2011-01-01
Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. PMID:21235532
Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y
2011-03-01
Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
Child, A W; Moore, B C; Vervoort, J D; Beutel, M W
2018-07-01
The upper Columbia River and associated valley systems are highly contaminated with metal wastes from nearby smelting operations in Trail, British Columbia, Canada (Teck smelter), and to a lesser extent, Northport, Washington, USA (Le Roi smelter). Previous studies have investigated depositional patterns of airborne emissions from these smelters, and documented the Teck smelter as the primary metal contamination source. However, there is limited research directed at whether these contaminants are bioavailable to aquatic organisms. This study investigates whether smelter derived contaminants are bioavailable to freshwater zooplankton. Trace metal (Zn, Cd, As, Sb, Pb and Hg) concentrations and Pb isotope compositions of zooplankton and sediment were measured in lakes ranging from 17 to 144 km downwind of the Teck smelter. Pb isotopic compositions of historic ores used by both smelters are uniquely less radiogenic than local geologic formations, so when zooplankton assimilate substantial amounts of smelter derived metals their compositions deviate from local baseline compositions toward ore compositions. Sediment metal concentrations and Pb isotope compositions in sediment follow significant (p < 0.001) negative exponential and sigmoidal patterns, respectively, as distance from the Teck smelting operation increases. Zooplankton As, Cd, and Sb contents were related to distance from the Teck smelter (p < 0.05), and zooplankton Pb isotope compositions suggest As, Cd, Sb and Pb from historic and current smelter emissions are biologically available to zooplankton. Zooplankton from lakes within 86 km of the Teck facility display isotopic evidence that legacy ore pollution is biologically available for assimilation. However, without water column data our study is unable to determine if legacy contaminants are remobilized from lake sediments, or erosional pathways from the watershed. Copyright © 2018 Elsevier Ltd. All rights reserved.
30 CFR 938.12 - State statutory, regulatory, and proposed program amendment provisions not approved.
Code of Federal Regulations, 2010 CFR
2010-07-01
... extent that it would allow the replaced water supply to be of a lesser quantity and quality than the premining water supply or does not provide for temporary replacement of water supplies. We are not approving Subsection (a)(1)(v) to the extent it would pass on operating and maintenance costs of a replacement water...
Gabner, S; Egerbacher, M; Gasse, H; Hewicker-Trautwein, M; Höltig, D; Waldmann, K-H; Blecha, F; Saalmüller, A; Hennig-Pauka, I
2017-10-01
Innate immunity is critically important for the outcome of infection in many diseases. It was previously shown that cathelicidin PR-39, an important porcine multifunctional host defence peptide, is elevated in bronchoalveolar lavage fluid and respiratory tract tissue after experimental infection with Actinobacillus pleuropneumoniae (A.pp.). To date, neutrophil polymorphonuclear leukocytes (PMNs) are thought to be the only source of PR-39. The aim of this study was to further characterize PR-39⁺ cells and selected immune cell populations in lung tissue during the peracute (7-10 hours), acute (2 days), reconvalescent (7 days) and chronic (21 days) stages of experimental infection with A.pp. serotype 2. In total, six mock-infected control pigs and 12 infected pigs were examined. Using immunofluorescence double-labeling, antibodies against PR-39 were combined with antibodies against CD3 (T-cells), CD79 (B-cells), Iba1 (activated macrophages), TTF-1 (lung epithelial cells expressing surfactant proteins), macrophage/L1 protein and myeloperoxidase (MPO, cells of the myeloid linage). In the peracute and acute phases of infection, total PR-39⁺ cells and myeloid linage cells increased, whereas CD3⁺ cells and TTF-1⁺ cells decreased. Double labeling revealed that most Macrophage/L1 protein+ cells and to a lesser extent MPO⁺ cells co-expressed PR-39. In addition, few bronchial epithelial cells and type 2 alveolar epithelial cells (both identified with TTF-1) produced PR-39. Occasionally, CD3⁺ T cells expressing PR-39 were seen in infected animals. Taken together, this study identifies cell types, other than PMNs, in lungs of A.pp.-infected pigs that are capable of producing PR-39. In addition, these findings provide further insights into the dynamics of different immune cell populations during A.pp.-infection.
Remediation System Evaluation, MacGillis and Gibbs Superfund Site
The site was a wood preserving facility that is no longer active. Key contaminants at the site includepentachlorophenol (PCP), chromium, and to a much lesser extent dioxin, arsenic, and polynucleararomatic hydrocarbons (PAHs).
NASA Astrophysics Data System (ADS)
Gaschnig, Richard M.; Rudnick, Roberta L.; McDonough, William F.; Kaufman, Alan J.; Valley, John W.; Hu, Zhaochu; Gao, Shan; Beck, Michelle L.
2016-08-01
The composition of the fine-grained matrix of glacial diamictites from the Mesoarchean, Paleoproterozoic, Neoproterozoic, and Paleozoic, collected from four modern continents, reflects the secular evolution of the average composition of the upper continental crust (UCC). The effects of localized provenance are present in some cases, but distinctive geochemical signatures exist in diamictites of the same age from different localities, suggesting that these are global signatures. Archean UCC, dominated by greenstone basalts and to a lesser extent komatiites, was more mafic, based on major elements and transition metal trace elements. Temporal changes in oxygen isotope ratios, rare earth elements, and high field strength elements indicate that the UCC became more differentiated and that tonalite-trondhjemite-granodiorite suites became less important with time, findings consistent with previous studies. We also document the concentrations of siderophile and chalcophile elements (Ga, Ge, Cd, In, Sn, Sb, W, Tl, Bi) and lithophile Be in the UCC through time, and use the data for the younger diamictites to construct a new estimate of average UCC along with associated uncertainties.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cook, C.M.; Lanaras, T.; Sgardelis, S.P.
The combustion of petroleum fuel and exhaust emissions are major sources of atmospheric pollution in cities which result in the deposition of toxic substances, particularly heavy metals, in the surface layers of soils. Lead in particular enters the environment from the use of tetraethyl lead as an antiknock agent for petrol engines constituting 21% of fine particles emitted from cars burning leaded petrol. Antiwear protectants incorporated in lubricants often contain Cd, Cr, Cu, Hg, Ni, Pb and/or Zn which are also released into the environment by inefficient engines and irresponsible dumping of engine oils. Zn from tyre wear and Cumore » from diesel engines also add considerably to the environmental metal burden. Lowering of the permitted lead content of petrol and the growing use of unleaded fuel are expected to lead to reductions in the environmental lead burden, however, until unleaded fuel becomes universally accepted lead contamination, particularly of roadside soils and vegetation is a major cause for concern. A direct relationship between car exhaust, the Pb content of needles of Abies alba and reduced growth has been observed and can extend hundreds of metres from major highways. Lead tolerance has been observed in higher plants growing mine waste soils and to a lesser extent on lead-contaminated roadside soils. Automobiles which are responsible for line sources of pollution emissions in rural and suburban areas have a more far-reaching impact on roadside vegetation, already under considerable stress, in urban areas. Information on heavy metal effects on vegetation in urban environments however, are scarce. Modeling and multivariate analysis of a few of the factors involved have provided only limited data related to plant performance in these complex environments. Therefore in this study, the extent of heavy metal pollution by Pb, Zn, Cu and Cd in soils and in dandelion plants in the city of Thessaloniki has been examined. 20 refs., 2 figs., 3 tabs.« less
Koch, Andrea; Knobloch, Jürgen; Dammhayn, Cathrin; Raidl, Maria; Ruppert, Andrea; Hag, Haitham; Rottlaender, Dennis; Müller, Katja; Erdmann, Erland
2007-11-01
Epidemiological evidence, in vitro studies and animal models suggest that exposure to the bacterial endotoxin lipopolysaccharide (LPS) can influence the development and severity of asthma. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 and 2 responses, it is unclear whether the LPS ligand TLR 4 is expressed on CD4(+) and CD8(+) T-lymphocytes and if so, whether LPS could modulate the T(H)1 or T(H)2 response in this context. The present authors have, therefore, examined the expression of TLR 4 on peripheral blood CD4(+) and CD8(+) T-lymphocytes using RT-PCR method and FACS analyses. Furthermore, the authors have studied the IL-12-induced expression of the T(H)1-associated cytokine INF-gamma and the IL-4-induced expression of the T(H)2-specific cytokine IL-5 in the presence of LPS using ELISA and compared nine atopic asthmatic subjects and eleven nonatopic normal volunteers. There was an increased anti-CD3/anti-CD28-induced IL-5 expression in T cells of asthmatics compared with normals (p<0.01). In the presence of IL-4 (10 ng/ml), there was an additional increase in IL-5 expression and this additional increase was greater in T cells of normals compared with asthmatics (p<0.05). There was an expression of INF-gamma in anti-CD3/anti-CD28-induced T-lymphocytes without differences between both groups (NS). In the presence of IL-12 (10 ng/ml), there was an increase in INF-gamma release without differences between normals and asthmatics (NS). In the presence of different concentrations of LPS (10 ng/ml, 1 mug/ml), there was a decrease in IL-4-induced IL-5 expression without differences in both groups, indicating an intact T(H)2 response to bacterial endotoxin LPS in asthma. Interestingly, LPS increased the IL-12-induced INF-gamma release in a concentration-dependent manner in T-lymphocytes of normals but this could not be found in T cells of asthmatics, indicating an impaired T(H)1 response to bacterial endotoxin LPS in asthma. In addition, there was a TLR 4 expression on CD4(+) T-lymphocytes of normals and to a lesser extent in asthmatics but this TLR 4 expression could not be found on CD8(+) T cells of both groups. In conclusion, there may be an impaired concentration-dependent LPS-induced T(H)1 rather than a T(H)2 response in allergic adult asthmatics compared with normal volunteers. One reason for this could be a reduced TLR 4 expression on CD4(+) T-lymphocytes of asthmatic subjects.
Cuda, Carla M.; Zeumer, Leilani; Sobel, Eric S.; Croker, Byron P.; Morel, Laurence
2010-01-01
The NZM2410-derived Sle1a lupus susceptibility locus induces activated autoreactive CD4+ T cells and reduces the number and function of Foxp3+ regulatory T cells. In this study, we first showed that Sle1a contributes to autoimmunity by increasing anti-nuclear antibody production when expressed on either NZB or NZW heterozygous genomes, and by enhancing the chronic graft vs. host disease response indicating an expansion of the autoreactive B cell pool. Screening two non-overlapping recombinants, the Sle1a.1 and Sle1a.2 intervals that cover the entire Sle1a locus, revealed that both Sle1a.1 and Sle1a.2 were necessary for the full Sle1a phenotype. Sle1a.1, and to a lesser extent Sle1a.2, significantly affected CD4+ T cell activation as well as Treg differentiation and function. Sle1a.2 also increased the production of autoreactive B cells. Since the Sle1a.1 and Sle1a.2 intervals contain only one and 15 known genes, respectively, this study considerably reduces the number of candidate genes responsible for the production of autoreactive T cells. These results also demonstrate that the Sle1 locus is an excellent model for the genetic architecture of lupus, in which a major obligate phenotype results from the co-expression of multiple genetic variants with individual weak effects. PMID:20445563
TIM-family proteins inhibit HIV-1 release
Li, Minghua; Ablan, Sherimay D.; Miao, Chunhui; Zheng, Yi-Min; Fuller, Matthew S.; Rennert, Paul D.; Maury, Wendy; Johnson, Marc C.; Freed, Eric O.; Liu, Shan-Lu
2014-01-01
Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV-1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors. PMID:25136083
He, Shao-heng; Zhang, Hui-yun; Zeng, Xiao-ning; Chen, Dong; Yang, Ping-chang
2013-01-01
The current definition of allergy is a group of IgE-mediated diseases. However, a large portion of patients with clinical manifestations of allergies do not exhibit elevated serum levels of IgE (sIgEs). In this article, three key factors, ie soluble allergens, sIgEs and mast cells or basophils, representing the causative factors, messengers and primary effector cells in allergic inflammation, respectively, were discussed. Based on current knowledge on allergic diseases, we propose that allergic diseases are a group of diseases mediated through activated mast cells and/or basophils in sensitive individuals, and allergic diseases include four subgroups: (1) IgE dependent; (2) other immunoglobulin dependent; (3) non-immunoglobulin mediated; (4) mixture of the first three subgroups. According to our proposed definition, pseudo-allergic-reactions, in which mast cell or basophil activation is not mediated via IgE, or to a lesser extent via IgG or IgM, should be non-IgE-mediated allergic diseases. Specific allergen challenge tests (SACTs) are gold standard tests for diagnosing allergies in vivo, but risky. The identification of surface membrane activation markers of mast cells and basophils (CD203c, CCR3, CD63, etc) has led to development of the basophil activation test (BAT), an in vitro specific allergen challenge test (SACT). Based on currently available laboratory allergy tests, we here propose a laboratory examination procedure for allergy. PMID:23974516
Synergy of Immune Checkpoint Blockade with a Novel Synthetic Consensus DNA Vaccine Targeting TERT.
Duperret, Elizabeth K; Wise, Megan C; Trautz, Aspen; Villarreal, Daniel O; Ferraro, Bernadette; Walters, Jewell; Yan, Jian; Khan, Amir; Masteller, Emma; Humeau, Laurent; Weiner, David B
2018-02-07
Immune checkpoint blockade antibodies are setting a new standard of care for cancer patients. It is therefore important to assess any new immune-based therapies in the context of immune checkpoint blockade. Here, we evaluate the impact of combining a synthetic consensus TERT DNA vaccine that has improved capacity to break tolerance with immune checkpoint inhibitors. We observed that blockade of CTLA-4 or, to a lesser extent, PD-1 synergized with TERT vaccine, generating more robust anti-tumor activity compared to checkpoint alone or vaccine alone. Despite this anti-tumor synergy, none of these immune checkpoint therapies showed improvement in TERT antigen-specific immune responses in tumor-bearing mice. αCTLA-4 therapy enhanced the frequency of T-bet + /CD44 + effector CD8 + T cells within the tumor and decreased the frequency of regulatory T cells within the tumor, but not in peripheral blood. CTLA-4 blockade synergized more than Treg depletion with TERT DNA vaccine, suggesting that the effect of CTLA-4 blockade is more likely due to the expansion of effector T cells in the tumor rather than a reduction in the frequency of Tregs. These results suggest that immune checkpoint inhibitors function to alter the immune regulatory environment to synergize with DNA vaccines, rather than boosting antigen-specific responses at the site of vaccination. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Limb, Jin-Kyung; Song, Doona; Jeon, Mijeong; Han, So-Yeop; Han, Gyoonhee; Jhon, Gil-Ja; Bae, Yun Soo; Kim, Jaesang
2015-04-01
In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34(+) haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. Copyright © 2012 John Wiley & Sons, Ltd.
Solar thermal technology evaluation, fiscal year 1982. Volume 1: Executive summary
NASA Technical Reports Server (NTRS)
1983-01-01
Three primary solar concepts the central receiver, parabolic dish, and parabolic trough are investigated. To a lesser extent, the hemispherical bowl and salt-gradient solar pond are also being studied. Each technology is described.
Forced Degradation Studies of Aloe Emodin and Emodin by HPTLC.
Narayanan, Sindhu; Jadhav, Aruna P; Kadam, V J
2015-01-01
Anthraquinones are natural phenolic compounds, which are reported to act as anti-aging, anti-inflammatory, antioxidant, anti-cancer, laxative and antitumor agents. They are abudant in plants like candle bush, aloes, cascara bark and rhubarb. The present work was to observe the effect of different forced degradation conditions by high-performance thin layer chromatography on potential markers i.e. aloe emodin and emodin. Both aloe emodin and emodin were subjected to various forced degradation studies such as oxidation, acid and alkaline hydrolysis, photolysis, hydrolytic and thermal degradation. Aloe emodin, was more susceptible to acid hydrolysis and degradation was found to a lesser extent under thermal degradation whereas significant degradation was observed under acid hydrolysis, lesser extent was observed under alkali hydrolysis for emodin. Forced degradation studies on aloe emodin and emodin gives information about its storage and intrinsic stability conditions considering the advanced pharmaceutical aspects of formulation.
Edens, John F
2009-03-01
Interest in conceptualizing the interpersonal style of individuals who engage in serious antisocial behavior has increased in recent years. This study examines the personality, psychopathological, and behavioral correlates of interpersonal dominance and warmth, as operationalized via scales of the Personality Assessment Inventory (L. Morey, 2007), across several samples of male prison inmates (combined N = 1,062). Consistent with theory, multivariate analyses indicated that low warmth and, to a lesser extent, high dominance were associated with antisocial and paranoid traits, specifically, and externalizing-spectrum psychopathology more generally, whereas borderline traits and internalizing-spectrum psychopathology were uniquely associated with low interpersonal warmth. Among smaller subsamples of inmates followed prospectively, high dominance and, to a lesser extent, low warmth predicted general and aggressive institutional misconduct, whereas dominance uniquely predicted staff ratings of treatment noncompliance/failure. (PsycINFO Database Record (c) 2009 APA, all rights reserved).
Study of CdTe quantum dots grown using a two-step annealing method
NASA Astrophysics Data System (ADS)
Sharma, Kriti; Pandey, Praveen K.; Nagpal, Swati; Bhatnagar, P. K.; Mathur, P. C.
2006-02-01
High size dispersion, large average radius of quantum dot and low-volume ratio has been a major hurdle in the development of quantum dot based devices. In the present paper, we have grown CdTe quantum dots in a borosilicate glass matrix using a two-step annealing method. Results of optical characterization and the theoretical model of absorption spectra have shown that quantum dots grown using two-step annealing have lower average radius, lesser size dispersion, higher volume ratio and higher decrease in bulk free energy as compared to quantum dots grown conventionally.
Heavy metals in soils and plants of the don river estuary and the Taganrog Bay coast
NASA Astrophysics Data System (ADS)
Minkina, T. M.; Fedorov, Yu. A.; Nevidomskaya, D. G.; Pol'shina, T. N.; Mandzhieva, S. S.; Chaplygin, V. A.
2017-09-01
Natural and anthropogenic factors determining the distribution and accumulation features of Pb, Cu, Zn, Cr, Ni, Cd, Mn, and As in the soil-plant system of the Don River estuary and the northern and southern Russian coasts of Taganrog Bay estuary have been studied. High mobility of Cu, Zn, Pb, and Cd has been revealed in alluvial soils. This is confirmed by the significant bioavailability of Cu, Zn, and, to a lesser degree, Cd and the technophily of Pb, which are accumulated in tissues of macrophytic plants. Statistically significant positive correlations have been found between the mobile forms of Cu, Zn, Cd, and Mn in the soil and the accumulation of metals in plants. Impact zones with increased metal contents in aquatic ecosystems can be revealed by bioindication from the morphofunctional parameters of macrophytic plants (with Typha L. as an example).
Rudolph, Henriette; Klopstein, Armelle; Gruber, Isabelle; Blatti, Claudia; Lyck, Ruth
2016-01-01
Although CD8+ T cells have been implied in the pathogenesis of multiple sclerosis (MS), the molecular mechanisms mediating CD8+ T‐cell migration across the blood–brain barrier (BBB) into the central nervous system (CNS) are ill defined. Using in vitro live cell imaging, we directly compared the multistep extravasation of activated CD4+ and CD8+ T cells across primary mouse brain microvascular endothelial cells (pMBMECs) as a model for the BBB under physiological flow. Significantly higher numbers of CD8+ than CD4+ T cells arrested on pMBMECs under noninflammatory and inflammatory conditions. While CD4+ T cells polarized and crawled prior to their diapedesis, the majority of CD8+ T cells stalled and readily crossed the pMBMEC monolayer preferentially via a transcellular route. T‐cell arrest and crawling were independent of G‐protein‐coupled receptor signaling. Rather, absence of endothelial ICAM‐1 and ICAM‐2 abolished increased arrest of CD8+ over CD4+ T cells and abrogated T‐cell crawling, leading to the efficient reduction of CD4+, but to a lesser degree of CD8+, T‐cell diapedesis across ICAM‐1null/ICAM‐2−/− pMBMECs. Thus, cellular and molecular mechanisms mediating the multistep extravasation of activated CD8+ T cells across the BBB are distinguishable from those involved for CD4+ T cells. PMID:27338806
Available nutrients in biochar
USDA-ARS?s Scientific Manuscript database
Biochar technology may contribute to the recovery and recycling of plant nutrients and thus add a fertilizer value to the biochar. Total nutrient content in biochars varies greatly and is mainly dependent on feedstock elemental composition and to a lesser extent on pyrolysis conditions. Availability...
Anxious or Depressed and Still Happy?
Spinhoven, Philip; Elzinga, Bernet M.; Giltay, Erik; Penninx, Brenda W. J. H.
2015-01-01
This study aimed to examine cross-sectionally to what extent persons with higher symptom levels or a current or past emotional disorder report to be less happy than controls and to assess prospectively whether time-lagged measurements of extraversion and neuroticism predict future happiness independent of time-lagged measurements of emotional disorders or symptom severity. A sample of 2142 adults aged 18–65, consisting of healthy controls and persons with current or past emotional disorder according to DSM-IV criteria completed self-ratings for happiness and emotional well-being and symptom severity. Lagged measurements of personality, symptom severity and presence of anxiety and depressive disorder at T0 (year 0), T2 (year 2) and T4 (year 4) were used to predict happiness and emotional well-being at T6 (year 6) controlling for demographics. In particular persons with more depressive symptoms, major depressive disorder, social anxiety disorder and comorbid emotional disorders reported lower levels of happiness and emotional well-being. Depression symptom severity and to a lesser extent depressive disorder predicted future happiness and emotional well-being at T6. Extraversion and to a lesser extent neuroticism also consistently forecasted future happiness and emotional well-being independent of concurrent lagged measurements of emotional disorders and symptoms. A study limitation is that we only measured happiness and emotional well-being at T6 and our measures were confined to hedonistic well-being and did not include psychological and social well-being. In sum, consistent with the two continua model of emotional well-being and mental illness, a ‘happy’ personality characterized by high extraversion and to a lesser extent low neuroticism forecasts future happiness and emotional well-being independent of concurrently measured emotional disorders or symptom severity levels. Boosting positive emotionality may be an important treatment goal for persons personally inclined to lower levels of happiness. PMID:26461261
DOT National Transportation Integrated Search
1996-07-01
The increasingly sophisticated demands placed on transportation planning models by the 1990 Clean Air Act Amendments (CAAA), the 1991 Intermodal Surface Transportation Efficiency Act (ISTEA), and to a lesser extent some earlier legislation, have led ...
Experimental demonstration of warm mix asphalt pavement on Rt. 4.
DOT National Transportation Integrated Search
2012-04-01
A number of new technologies have been developed to lower the production and placement temperatures : of hot-mix asphalt (HMA). Generically, these technologies are referred to as warm-mix asphalt (WMA). : In Europe and to a lesser extent in North Ame...
Reconsidering Division Cavalry Squadrons
2017-05-25
mechanized cavalry against German, and to a lesser extent, Japanese combined arms forces cemented its status as a distinctive sub-branch in its rapidly...Integration Center, TRADOC, 1 June 2016 Mahler, Michael D. Ringed in Steel : Armored Cavalry, Vietnam 1967-68. Novato, CA: Presidio Press, 1986
Blaheta, R A; Hailer, N P; Brude, N; Wittig, B; Leckel, K; Oppermann, E; Bachmann, M; Harder, S; Cinatl, J; Scholz, M; Bereiter-Hahn, J; Weber, S; Encke, A; Markus, B H
2000-02-27
Cyclosporine A (CsA) and tacrolimus prevent proliferation but not transendothelial migration of alloreactive lymphocytes into donor organs. As a result, serious adverse effects, such as nephrotoxicity and neurotoxicity, have been observed under CsA/tacrolimus therapy. The incorporation of new drugs with infiltration blocking properties might enhance the efficacy of the current immunosuppressive protocol, allowing lower CsA/tacrolimus dosage. Because Ca2+ plays a critical role in cell-cell interaction, the Ca2+-channel blocker verapamil might be a good cany. didate for supporting CsA/tacrolimus-based therapy. A T-cell endothelial cell coculture model or immobilized immunoglobulin G globulin chimeras were employed to investigate how S- and R- verapamil interfere with the lymphocytic infiltration process. The expression and arrangement of membranous adhesion receptors and cytoskeletal F-actin filaments were analyzed by fluorometric method in the presence of. verapamil. Both verapamil enantiomers strongly inhibited lymphocyte infiltration. CD4+ and CD8+ T-cells were influenced to a similar extent with regard to horizontal locomotion (CD4+=CD8+), but to a different extent with regard to adhesion and penetration (CD4+ > CD8+). Moreover, penetration was blocked to a higher extent than was adhesion. ID50-values were 31 microM (CD4+-adhesion) and 11 microM (CD4+-penetration). Verapamil reduced P-selectin expression on endothelial cells and effectively down-regulated binding of T-cells to immobilized P-selectin immunoglobulin G globulins (ID50=4.4 microM; CD4+). A verapamil-induced reduction of intracellular F-actin in T-lymphocytes was proven to be mainly responsible for diminished cell locomotion. The prevention of CD4+ T-cell penetration by verapamil might argue for its use as an adjunct to CsA/tacrolimus-based immunosuppressive therapy.
Pneumolysin mediates heterotypic aggregation of neutrophils and platelets in vitro.
Nel, Jan G; Durandt, Chrisna; Theron, Annette J; Tintinger, Gregory R; Pool, Roger; Richards, Guy A; Mitchell, Timothy J; Feldman, Charles; Anderson, Ronald
2017-06-01
Platelets orchestrate the inflammatory activities of neutrophils, possibly contributing to pulmonary and myocardial damage during severe pneumococcal infection. This study tested the hypothesis that the pneumococcal toxin, pneumolysin (Ply), activates production of platelet-activating factor (PAF) and thromboxane A 2 (TxA 2 ) by neutrophils, these bioactive lipids being potential mediators of neutrophil:platelet (NP) networking. The effects of recombinant Ply (10-80 ng mL -1 ) on the production of PAF and TxA 2 by isolated neutrophils were measured using ELISA procedures, and NP aggregation by flow cytometry. Exposure of neutrophils to Ply induced production of PAF and, to a lesser extent, TxA 2 , achieving statistical significance at ≥20 ng mL -1 of the toxin. In the case of NP interactions, Ply promoted heterotypic aggregation which was dependent on upregulation of P-selectin (CD62P) and activation of protease-activated receptor 1 (PAR1), attaining statistical significance at ≥10 ng mL -1 of the toxin, but did not involve either PAF or TxA 2 . Ply induces synthesis of PAF and TxA 2, by human neutrophils, neither of which appears to contribute to the formation of NP heterotypic aggregates in vitro, a process which is seemingly dependent on CD62P and PAR1. These pro-inflammatory activities of Ply may contribute to the pathogenesis of pulmonary and myocardial injury during severe pneumococcal infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Mukai, Kaori; Karasuyama, Hajime; Kabashima, Kenji; Kubo, Masato; Galli, Stephen J
2017-05-01
There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3 -deficient and c- kit mutant Kit W / W-v mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit W-sh / W-sh mice and two types of mast cell-deficient mice that have normal c- kit ("Hello Kit ty" and MasTRECK mice) confirmed prior work in Kit W / W-v mice that suggested that mast cells play an important role in S. venezuelensis egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to S. venezuelensis By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with S. venezuelensis Studies in basophil-deficient Mcpt8 DTR mice revealed a small but significant contribution of basophils to S. venezuelensis egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4 + T cells and ILC2 cells, IgG, FcRγ, and, to a lesser extent, IgE and FcεRI contribute to effective immunity in primary S. venezuelensis infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary S. venezuelensis infection is as follows: CD4 + T cells/ILC2 cells, IgG, and FcRγ>mast cells>IgE and FcεRI>basophils. In contrast, in secondary S. venezuelensis infection, our evidence indicates that the presence of CD4 + T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles. Copyright © 2017 American Society for Microbiology.
Mills, Margaret G; Gallagher, Evan P
2017-01-01
Chemical-induced oxidative stress and the biochemical pathways that protect against oxidative damage are of particular interest in the field of toxicology. To rapidly identify oxidative stress-responsive gene expression changes in zebrafish, we developed a targeted panel of antioxidant genes using the Affymetrix QuantiGene Plex (QGP) platform. The genes contained in our panel include eight putative Nrf2 (Nfe2l2a)-dependent antioxidant genes (hmox1a, gstp1, gclc, nqo1, prdx1, gpx1a, sod1, sod2), a stress response gene (hsp70), an inducible DNA damage repair gene (gadd45bb), and three reference genes (actb1, gapdh, hprt1). We tested this platform on larval zebrafish exposed to tert-butyl hydroperoxide (tBHP) and cadmium (Cd), two model oxidative stressors with different modes of action, and compared our results with those obtained using the more common quantitative PCR (qPCR) method. Both methods showed that exposure to tBHP and Cd induced expression of prdx1, gstp1, and hmox1a (2- to 12-fold increase via QGP), indicative of an activated Nrf2 response in larval zebrafish. Both compounds also elicited a general stress response as reflected by elevation of hsp70 and gadd45bb, with Cd being the more potent inducer. Transient changes were observed in sod2 and gpx1a expression, whereas nqo1, an Nrf2-responsive gene in mammalian cells, was minimally affected by either tBHP or Cd chemical exposures. Developmental expression analysis of the target genes by QGP revealed marked upregulation of sod2 between 0-96hpf, and to a lesser extent, of sod1 and gstp1. Once optimized, QGP analysis of these experiments was accomplished more rapidly, using far less tissue, and at lower total costs than qPCR analysis. In summary, the QGP platform as applied to higher-throughput zebrafish studies provides a reasonable cost-effective alternative to qPCR or more comprehensive transcriptomics approaches to rapidly assess the potential for chemicals to elicit oxidative stress as a mechanism of chemical toxicity.
Villanueva-Lizama, Liliana E; Cruz-Chan, Julio V; Aguilar-Cetina, Amarú Del C; Herrera-Sanchez, Luis F; Rodriguez-Perez, Jose M; Rosado-Vallado, Miguel E; Ramirez-Sierra, Maria J; Ortega-Lopez, Jaime; Jones, Kathryn; Hotez, Peter; Bottazzi, Maria Elena; Dumonteil, Eric
2018-01-01
Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.
Comparison of CIGS solar cells made with different structures and fabrication techniques
Mansfield, Lorelle M.; Garris, Rebekah L.; Counts, Kahl D.; ...
2016-11-03
Cu(In, Ga)Se2 (CIGS)-based solar cells from six fabricators were characterized and compared. The devices had differing substrates, absorber deposition processes, buffer materials, and contact materials. The effective bandgaps of devices varied from 1.05 to 1.22 eV, with the lowest optical bandgaps occurring in those with metal-precursor absorber processes. Devices with Zn(O, S) or thin CdS buffers had quantum efficiencies above 90% down to 400 nm. Most voltages were 250-300 mV below the Shockley-Queisser limit for their bandgap. Electroluminescence intensity tracked well with the respective voltage deficits. Fill factor (FF) was as high as 95% of the maximum for each device'smore » respective current and voltage, with higher FF corresponding to lower diode quality factors (~1.3). An in-depth analysis of FF losses determined that diode quality reflected in the quality factor, voltage-dependent photocurrent, and, to a lesser extent, the parasitic resistances are the limiting factors. As a result, different absorber processes and device structures led to a range of electrical and physical characteristics, yet this investigation showed that multiple fabrication pathways could lead to high-quality and high-efficiency solar cells.« less
NASA Technical Reports Server (NTRS)
Singh, J. J.; Sentell, R. J.; Khandelwal, G. S.
1976-01-01
Aerosols emitted from two oil-fired heating plants were aerodynamically separated into eight size groups and were analyzed using the photon-induced X-ray emission (PIXE) technique. It was found that Zn, Mo, Ag, and Pb, and (to a lesser extent) Cd, have a tendency to concentrate preferentially on the smaller aerosols. All of these elements, in certain chemical forms, are known to be toxic. Zinc and molybdenum, although present in low concentrations in the parent fuels, show the strongest tendencies to be concentrated in finer aerosols. Selenium, previously reported to show a very strong tendency to concentration in finer fly ash from coal-fired power plants shows little preference for surface residence. Vanadium, which occurs in significant concentration in the oil fuels for both plants, also shows little preference for surface concentration. Even though the absolute concentrations of the toxic elements involved are well below the safety levels established by the National Institute for Occupational Safety and Health (NIOSH), it would be advisable to raise the heights of the heating-plant exhaust chimneys well above the neighborhood buildings to insure more efficient aerosol dispersal.
Comparison of CIGS solar cells made with different structures and fabrication techniques
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mansfield, Lorelle M.; Garris, Rebekah L.; Counts, Kahl D.
Cu(In, Ga)Se2 (CIGS)-based solar cells from six fabricators were characterized and compared. The devices had differing substrates, absorber deposition processes, buffer materials, and contact materials. The effective bandgaps of devices varied from 1.05 to 1.22 eV, with the lowest optical bandgaps occurring in those with metal-precursor absorber processes. Devices with Zn(O, S) or thin CdS buffers had quantum efficiencies above 90% down to 400 nm. Most voltages were 250-300 mV below the Shockley-Queisser limit for their bandgap. Electroluminescence intensity tracked well with the respective voltage deficits. Fill factor (FF) was as high as 95% of the maximum for each device'smore » respective current and voltage, with higher FF corresponding to lower diode quality factors (~1.3). An in-depth analysis of FF losses determined that diode quality reflected in the quality factor, voltage-dependent photocurrent, and, to a lesser extent, the parasitic resistances are the limiting factors. As a result, different absorber processes and device structures led to a range of electrical and physical characteristics, yet this investigation showed that multiple fabrication pathways could lead to high-quality and high-efficiency solar cells.« less
Madlambayan, Gerard J.; Butler, Jason M.; Hosaka, Koji; Jorgensen, Marda; Fu, Dongtao; Guthrie, Steven M.; Shenoy, Anitha K.; Brank, Adam; Russell, Kathryn J.; Otero, Jaclyn; Siemann, Dietmar W.
2009-01-01
Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1α (SDF-1α) and its mobilizing effects on BM. Blocking SDF-1α activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133+CXCR4+ myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1α. The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field. PMID:19717647
Starch Characteristics Linked to Gluten-Free Products.
Horstmann, Stefan W; Lynch, Kieran M; Arendt, Elke K
2017-04-06
The increasing prevalence of coeliac disease (CD) and gluten-related disorders has led to increasing consumer demand for gluten-free products with quality characteristics similar to wheat bread. The replacement of gluten in cereal-based products remains a challenge for scientists, due to its unique role in network formation, which entraps air bubbles. When gluten is removed from a flour, starch is the main component left. Starch is used as gelling, thickening, adhesion, moisture-retention, stabilizing, film forming, texturizing and anti-staling ingredient. The extent of these properties varies depending on the starch source. The starches can additionally be modified increasing or decreasing certain properties of the starch, depending on the application. Starch plays an important role in the formulation of bakery products and has an even more important role in gluten-free products. In gluten-free products, starch is incorporated into the food formulation to improve baking characteristics such as the specific volume, colour and crumb structure and texture. This review covers a number of topics relating to starch; including; an overview of common and lesser researched starches; chemical composition; morphology; digestibility; functionality and methods of modification. The emphasis of this review is on starch and its properties with respect to the quality of gluten-free products.
Hein, J.R.; Koschinsky, A.; McIntyre, B.R.
2005-01-01
Mercury- and silver-enriched ferromanganese oxide crusts were recovered at water depths of 1,750 tol,300 m from La Victoria knoll, located about 72 km off the coast of northern Baja California. No other ferromanganese precipitate found so far in the modern ocean basins is similarly enriched in Hg and Ag. The precipitates consist of submetallic gray, brecciated, Mn oxide layers overlain by brown earthy, laminated Fe-Mn oxide crusts. Both oxide types are rich in Hg (to 10 ppm) and Ag (to 5.5 ppm). The Mn-rich layers are composed of ??MnO2, with lesser amounts of 10A?? and 7A?? manganates, whereas the Mn phase in the Fe-Mn crusts is solely ??MnO2. The Fe phase in both layers is X-ray amorphous. Established criteria for distinguishing hydrothermal versus hydrogenetic crusts indicate that the Mn-rich layers are predominantly of low-temperature hydrothermal origin, whereas the Fe-Mn crusts are hydrogenetic, although there is some overlap in the source of chemical components in both types. La Victoria knoll is uplifted continental basement rock with basalt, andesite, and schist cropping out at the surface; the knoll may have an intrusive core. The Hg and Ag were derived from leaching by hydrothermal fluids of organic matter-rich sediments in basins adjacent to La Victoria knoll and, to a lesser extent, from continental basement rocks underlying the knoll and adjacent basins. Both rock types are notably enriched in Ag and Hg. Faults were the main fluid transport pathway, and hydrothermal circulation was driven by high heat flow associated with thinned crust. Other elements derived from the hydrothermal fluids include Tl, Cd, Cr, and Li. The main host for Hg and Ag is FeOOH, although MnO2 likely hosts some of the Ag. Minor sulfide and barite also may contain small amounts of these metals. Possible analogs in the geologic record for this deposit type are found in the Basin and Range province of the western United States and Mexico. The discovery highlights the fact that fluids circulating along faults in the offshore California borderland are transporting potentially toxic metals (Hg, Ag, Tl, As, Cd, Cr, Pb, and Ni) and depositing them on and just below the ocean floor. ?? 2005 Society of Economic Geologists, Inc.
OZONE GENERATION IN DC-ENERGIZED ELECTROSTATIC PRECIPATORS
Ozone emissions from a short wire-plate precipitator and three commercial electronic air cleaners were measured. Ozone generation was most strongly affected by the corona current and polarity of the discharge electrode. To a lesser extent, the type of corona (i.e. whether tuft or...
DOT National Transportation Integrated Search
2008-06-01
More jurisdictions including states and metropolitan areas are establishing traffic management centers to assist in reducing congestion. To a lesser extent, these centers are helpful in providing information that assists engineers in making such adju...
Use of warm mix asphalt pavement on Route 9, in Durham.
DOT National Transportation Integrated Search
2012-06-01
A number of new technologies have been developed to lower the production and placement temperatures : of hot-mix asphalt (HMA). Generically, these technologies are referred to as warm-mix asphalt (WMA). : In Europe and to a lesser extent in North Ame...
Effects of portland cement particle size on heat of hydration : [summary].
DOT National Transportation Integrated Search
2013-12-01
Generally, when materials are heated (or cooled), : they expand (or contract) to a greater or lesser : extent. Even a material as rock-like as concrete : is susceptible to thermal effects, and expansion : joints are used for this reason: to allow con...
No Abstract - first paragraph of INTRODUCTION
Publicly supported compilations of mutagenicity and carcinogenicity data are available
for a significant number and variety of environmental and industrial chemicals and, to a lesser
extent, pharmaceutical chemicals. T...
Electromagnetic articulography treatment for an adult with Broca's aphasia and apraxia of speech.
Katz, W F; Bharadwaj, S V; Carstens, B
1999-12-01
Electromagnetic articulography (EMA) was explored as a means of remediating [s]/[symbol in text] articulation deficits in the speech of an adult with Broca's aphasia and apraxia of speech. Over a 1-month period, the subject was provided with 2 different treatments in a counterbalanced procedure: (1) visually guided biofeedback concerning tongue-tip position and (2) a foil treatment in which a computer program delivered voicing-contrast stimuli for simple repetition. Kinematic and perceptual data suggest improvement resulting from visually guided biofeedback, both for nonspeech oral and, to a lesser extent, speech motor tasks. In contrast, the phonetic contrast treated in the foil condition showed only marginal improvement during the therapy session, with performance dropping back to baseline 10 weeks post-treatment. Although preliminary, the findings suggest that visual biofeedback concerning tongue-tip position can be used to treat nonspeech oral and (to a lesser extent) speech motor behavior in adults with Broca's aphasia and apraxia of speech.
Hernández-Pellón, A; Nischkauer, W; Limbeck, A; Fernández-Olmo, I
2018-04-25
The content of metal(loid)s in particulate matter (PM) is of special concern due to their contribution to overall (PM) toxicity. In this study, the bioaccessibility and human health risk of potentially toxic metal(loid)s associated with PM 10 were investigated in two areas of the Cantabrian region (northern Spain) with different levels of exposure: an industrial area mainly influenced by a ferromanganese alloy plant; and an urban area consisting mainly of residential and commercial activities, but also affected, albeit to a lesser extent by the ferroalloy plant. Total content and bioaccessible fractions in simulated lung fluids (SLFs) of Fe, Mn, Zn, Ni, Cu, Sb, Mo, Cd and Pb were determined by ICP-MS. Gamble's solution and artificial lysosomal fluid (ALF) were used to mimic different conditions inside the human respiratory system. A health risk assessment was performed based on the United States Environmental Protection Agency's (USEPA) methodology. Most metal(loid)s showed moderate and high bioaccessibility in Gamble's solution and ALF, respectively. Despite the high variability between the samples, metal(loid) bioaccessibility was found to be higher on average at the industrial site, suggesting a greater hazard to human health in the proximity of the main metal(loid) sources. Based on the results of the risk assessment, the non-carcinogenic risk associated with Mn exposure was above the safe limit (HQ> 1) under all the studied scenarios at the industrial site and under some specific scenarios at the urban location. The estimated carcinogenic inhalation risk for Cd exposure at the industrial site was found to be within the range between 1.0 × 10 -6 to 1.0 × 10 -4 (uncertainty range) under some scenarios. The results obtained in this study indicate that Mn and Cd inhalation exposure occurring in the vicinities of the studied areas may pose a human health risk. Copyright © 2018 Elsevier Inc. All rights reserved.
Kaba, Nubia K.; Schultz, Joanne; Law, Foon-Yee; Lefort, Craig T.; Martel-Gallegos, Guadalupe; Kim, Minsoo; Waugh, Richard E.; Arreola, Jorge; Knauf, Philip A.
2008-01-01
Ischemia-reperfusion injury is a common pathological occurrence causing tissue damage in heart attack and stroke. Entrapment of neutrophils in the vasculature during ischemic events has been implicated in this process. In this study, we examine the effects that lactacidosis and consequent reductions in intracellular pH (pHi) have on surface expression of adhesion molecules on neutrophils. When human neutrophils were exposed to pH 6 lactate, there was a marked decrease in surface L-selectin (CD62L) levels, and the decrease was significantly enhanced by inclusion of Na+/H+ exchanger (NHE) inhibitor 5-(N,N-hexamethylene)amiloride (HMA). Similar effects were observed when pHi was reduced while maintaining normal extracellular pH, by using an NH4Cl prepulse followed by washes and incubation in pH 7.4 buffer containing NHE inhibitors [HMA, cariporide, or 5-(N,N-dimethyl)amiloride (DMA)]. The amount of L-selectin shedding induced by different concentrations of NH4Cl in the prepulse correlated with the level of intracellular acidification with an apparent pK of 6.3. In contrast, β2-integrin (CD11b and CD18) was only slightly upregulated in the low-pHi condition and was enhanced by NHE inhibition to a much lesser extent. L-selectin shedding was prevented by treating human neutrophils with inhibitors of extracellular metalloproteases (RO-31-9790 and KD-IX-73-4) or with inhibitors of intracellular signaling via p38 MAP kinase (SB-203580 and SB-239063), implying a transmembrane effect of pHi. Taken together, these data suggest that the ability of NHE inhibitors such as HMA to reduce ischemia-reperfusion injury may be related to the nearly complete removal of L-selectin from the neutrophil surface. PMID:18829897
Witt, Emitt C.
2016-01-01
Historic lead and zinc (Pb-Zn) mining in southeast Missouri’s ―Old Lead Belt‖ has left large chat piles dominating the landscape where prior to 1972 mining was the major industry of the region. As a result of variable beneficiation methods over the history of mining activity, these piles remain with large quantities of unrecovered Pb and Zn and to a lesser extent cadmium (Cd). Quantifying the residual content of trace metals in chat piles is problematic because of the extensive field effort that must go into collecting elevation points for volumetric analysis. This investigation demonstrates that publicly available lidar point data from the U.S. Geological Survey 3D Elevation Program (3DEP) can be used to effectively calculate chat pile volumes as a method of more accurately estimating the total residual trace metal content in these mining wastes. Five chat piles located in St. Francois County, Missouri, were quantified for residual trace metal content. Utilizing lidar point cloud data collected in 2011 and existing trace metal concentration data obtained during remedial investigations, residual content of these chat piles ranged from 9247 to 88,579 metric tons Pb, 1925 to 52,306 metric tons Zn, and 51 to 1107 metric tons Cd. Development of new beneficiation methods for recovering these constituents from chat piles would need to achieve current Federal soil screening standards. To achieve this for the five chat piles investigated, 42 to 72% of residual Pb would require mitigation to the 1200 mg/kg Federal non-playground standard, 88 to 98% of residual Zn would require mitigation to the Ecological Soil Screening level (ESSL) for plant life, and 70% to 98% of Cd would require mitigation to achieve the ESSL. Achieving these goals through an existing or future beneficiation method(s) would remediate chat to a trace metal concentration level that would support its use as a safe agricultural soil amendment.
Wagner, Stephen J; Skripchenko, Andrey; Myrup, Andrew; Thompson-Montgomery, Dedeene; Awatefe, Helen; Moroff, Gary
2010-05-01
Commercially available additive solutions (ASs) require 30% to 35% plasma for optimal storage of platelets (PLTs). PLTs suspended in M-sol, a bicarbonate-based experimental platelet additive solution (PAS), maintain in vitro PLT properties during storage with low levels of plasma (< or =5%). Four different formulations of M-sol were prepared at the optimal pH (6.1): M-sol, M-sol without calcium, M-sol without citric acid, and M-sol without calcium and citric acid. Apheresis PLT units (100% plasma) were equally divided into five 50-mL aliquots in PL732 containers, centrifuged, and resuspended to prepare units suspended in the four different PASs (95%) with 5% plasma and 1 unit in 100% plasma. Units (n = 10) were stored under standard conditions and assayed for in vitro properties on Days 1, 5, and 7. The data were analyzed by analysis of variance for repeated measures (n = 10, p < 0.001). On Day 5 of storage, PLTs suspended in the M-sol formulation containing calcium but lacking citric acid had similar pH, extent of shape change (ESC) values, and percentage of CD62-positive PLTs and greater hypotonic shock response (HSR) and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma. In contrast, PLTs suspended in the M-sol formulation lacking calcium had lesser ESC values, greater percentage of CD62-positive PLTs, and similar HSR values and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma on Day 5 (p < 0.001). Calcium plays an important role in maintaining CD62-negative PLTs and relatively high ESC in 5% plasma. The removal of citric acid from M-sol may improve PLT storage properties with low plasma levels.
Manousou, P; Kolios, G; Valatas, V; Drygiannakis, I; Bourikas, L; Pyrovolaki, K; Koutroubakis, I; Papadaki, H A; Kouroumalis, E
2010-11-01
Human colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known to attract CCR3-expressing, Th2-polarized lymphocytes. We studied constitutive and inflammation-induced expression and production of CCR3 together with its ligands in the colon and peripheral blood of patients with inflammatory bowel disease (IBD) by flow cytometry, reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the regulated expression of these chemokines by RT–PCR and ELISA using cultured human epithelial cell lines. A higher fraction of peripheral T lymphocytes were found to be positive for CCR3 in patients with ulcerative colitis (UC) compared to Crohn’s disease (CD), while almost no CCR3(+) T cells were found in normal controls (NC). Similarly, higher and more frequent expression of CCR3 was observed in colonic biopsies from patients with UC, regardless of the disease activity, when compared to CD or NCs. Serum CCL11/eotaxin-1 was increased significantly in UC (306 ± 87 pg/ml) and less so in CD (257 ± 43 pg/ml), whereas CCL24/eotaxin-2, and CCL26/eotaxin-3 were increased only in UC. Colonic expression of the three chemokines was minimal in NCs but high in inflammatory bowel diseases (especially UC) and was independent of disease activity. Th2, and to a lesser extent Th1, cytokines were able to induce expression and production of all three eotaxins from colonic epithelial cells in culture. CCR3 and ligands over-expression would appear to be a characteristic of UC. The production of CCR3 ligands by human colonic epithelial cells suggests further that epithelium can play a role in modulating pathological T cell-mediated mucosal inflammation.
Oxidation of thymidylate synthase by inorganic compounds.
Aull, J L; Ivery, T C; Daron, H H
1984-10-01
Thymidylate synthase from methotrexate-resistant Lactobacillus casei was rapidly and completely inactivated by low concentrations of permanganate, periodate, or potassium triiodide at 0 degree C. The enzyme was not inactivated to any appreciable extent by iodate, iodide, ferricyanate, iodosobenzoate, or hydrogen peroxide. The inactivation by permanganate was retarded by the substrate 2'-deoxyuridylate and, to a lesser extent, by phosphate. Titration of enzyme activity with permanganate showed that two moles of permanganate were required to completely inactivate one mole of thymidylate synthase.
Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat.
Olatunji-Bello, I I; Odusanya, A J; Raji, I; Ladipo, C O
2007-04-01
Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel.
Arcos Vieira, Luisa
2009-03-01
Health care in minors and incompetent patients implies problems with regard to the extent of the impact that those circumstances must have on their right to be informed and on their capacity for giving informed consent and, consequently, on a greater or lesser importance of third party intervention. This article aims to contribute some considerations about the approach of Spanish law to these questions, in order to show the extent to which those patients' autonomy has been recognized.
Tenth anniversary special issue of the Journal of Breath Research: looking forward
The Journal of Breath Research has now reached its 10th anniversary of publication. From the general public’s perspective, breath analysis had always revolved around drinking and driving, and to some lesser extent pulmonary function testing of athletes. However, at the ince...
Information Processing and Human Abilities
ERIC Educational Resources Information Center
Kirby, John R.; Das, J. P.
1978-01-01
The simultaneous and successive processing model of cognitive abilities was compared to a traditional primary mental abilities model. Simultaneous processing was found to be primarily related to spatial ability; and to a lesser extent, to memory and inductive reasoning. Subjects were 104 fourth-grade urban males. (Author/GD C)
Use of warm mix asphalt pavement on Interstate 95, Carmel to Hampden, northbound.
DOT National Transportation Integrated Search
2012-06-01
A number of new technologies have been developed to lower the production and placement temperatures : of hot-mix asphalt (HMA). Generically, these technologies are referred to as warm-mix asphalt (WMA). : In Europe and to a lesser extent in North Ame...
NASA Astrophysics Data System (ADS)
Cui, Shuang; Zhou, Qixing; Chao, Lei
2007-01-01
The absorption and accumulation of Pb, Zn, Cu and Cd in some endurant weed plant species that survived in an old smeltery in Liaoning, China, were systematically investigated. Potential hyperaccumulative characteristics of these species were also discussed. The results showed that metal accumulation in plants differed with species, tissues and metals. Endurant weed plants growing in this contaminated site exhibited high metal adaptability. Both the metal exclusion and detoxification tolerance strategies were involved in the species studied. Seven species for Pb and four species for Cd were satisfied for the concentration time level standard for hyperaccumulator. Considering translocation factor (TF) values, one species for Pb, seven species for Zn, two species for Cu and five species for Cd possessed the characteristic of hyperaccumulator. Particularly, Abutilon theophrasti Medic, exhibited strong accumulative ability to four heavy metals. Although enrichment coefficients of all samples were lesser than 1 and the absolute concentrations didn’t reach the standard, species mentioned above were primarily believed to be potential hyperaccumulators.
Alvarez, Maite; Bouchlaka, Myriam N.; Sckisel, Gail D.; Sungur, Can M.; Chen, Mingyi; Murphy, William J.
2014-01-01
Due to increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL2 with antibodies to neutralize TGFβ, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater anti-tumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK progenitors and activated CD8 T cells resulting in the observed anti-tumor effects. Combination immunotherapy was also accompanied with lesser toxicities than IL2 therapy alone. Additionally, we observed a dual competition between NK and activated CD8 T cells such that after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory anti-tumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK and CD8 T cells in response to systemic activation. PMID:25000978
Evaluation of Selected Recycling Curricula: Educating the Green Citizen.
ERIC Educational Resources Information Center
Boerschig, Sally; De Young, Raymond
1993-01-01
Solid waste curricula from various programs around the country were reviewed using eight variables identified as predictors of conservation behavior. Scores demonstrated that solid waste curricula focus mainly on knowledge and include, to a lesser extent, attitude change and action strategies. Lists the 14 programs evaluated in the study. (MDH)
7 CFR 51.318 - Serious damage.
Code of Federal Regulations, 2012 CFR
2012-01-01
... Standards for Grades of Apples Definitions § 51.318 Serious damage. “Serious damage” means any specific... or shipping quality of the apple. In addition, specific defect measurements are based on an apple... combination of lesser bruises which detract from the appearance or edible quality of the apple to an extent...
7 CFR 51.318 - Serious damage.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Standards for Grades of Apples Definitions § 51.318 Serious damage. “Serious damage” means any specific... or shipping quality of the apple. In addition, specific defect measurements are based on an apple... combination of lesser bruises which detract from the appearance or edible quality of the apple to an extent...
7 CFR 51.318 - Serious damage.
Code of Federal Regulations, 2011 CFR
2011-01-01
... Standards for Grades of Apples Definitions § 51.318 Serious damage. “Serious damage” means any specific... or shipping quality of the apple. In addition, specific defect measurements are based on an apple... combination of lesser bruises which detract from the appearance or edible quality of the apple to an extent...
The Continuing Role of Physical Attractiveness in Marriage.
ERIC Educational Resources Information Center
Margolin, Leslie; White, Lynn
1987-01-01
Examined the role of physical attractiveness in marriage. Showed that the decreases in physical appearance normally associated with aging affected husbands' responses to their wives more than wives' to their husbands. Husband's sexual interest, happiness in the sexual relationship, and, to a lesser extent, unfaithfulness were affected. (Author/ABB)
Signal Estimation, Inverse Scattering, and Problems in One and Two Dimensions.
1982-11-01
attention to implication for new estimation algorithms and signal processing and, to a lesser extent, for system theory . The publications resulting...from the work are listed by category and date. They are briefly organized and reviewed under five major headings: (1) Two-Dimensional System Theory ; (2
Current Themes in Integration. The Exceptional Child. Monograph Number Two.
ERIC Educational Resources Information Center
Ashman, Adrian F., Ed.
1991-01-01
This collection represents diverse views and opinions concerning integration of individuals with disabilities in Australia and, to a lesser extent, New Zealand. The objective in producing the volume is to stimulate thought and further debate about the policies and practices associated with integration, and numerous perceptions of integration are…
The Use of Haptic Display Technology in Education
ERIC Educational Resources Information Center
Barfield, Woodrow
2009-01-01
The experience of "virtual reality" can consist of head-tracked and stereoscopic virtual worlds, spatialized sound, haptic feedback, and to a lesser extent olfactory cues. Although virtual reality systems have been proposed for numerous applications, the field of education is one particular application that seems well-suited for virtual…
Lessons from Abroad: Whatever Happened to Pedagogy?
ERIC Educational Resources Information Center
Elliott, Julian G.
2014-01-01
This paper considers attempts to import pedagogic practices from other educational systems. In so doing, it focuses upon policymakers' attempts to: (a) import interactive whole class teaching approaches to the UK (and, to a lesser extent, the US); and (b) export learner-centred pedagogies, largely derived from Anglo-American theorising and…
Analysis of grain quality at receival
USDA-ARS?s Scientific Manuscript database
With an emphasis on wheat and to a lesser extent, barley, we describe the series of post harvest transfer stages of grain between the first point of sale and the export terminal. At each transfer point, a document accompanies a grain consignment that pertains to its quality (class, purity, sanitatio...
Setting Standards for Student Assessment
ERIC Educational Resources Information Center
Pell, Godfrey; Roberts, T. E.
2006-01-01
The increase in litigation by students who are dissatisfied with their assessment, and to a lesser extent the time and monetary costs of student appeals makes it imperative that institutions adopt a robust assessment strategy. The concern of consumers with respect to professional services offered by students after graduation is also an issue. This…
49 CFR 236.1011 - PTC Implementation Plan content requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... the following risk factors by track segment: (i) Segment traffic characteristics such as typical...; (4) How, to the extent practical, the PTC system will be implemented to address areas of greater risk to the public and railroad employees before areas of lesser risk; (5) The sequence and schedule in...
Sorting out pestiviral phylogeny: A tale of viral swarms, red herrings, and sons of Bs
USDA-ARS?s Scientific Manuscript database
Initially three species, border disease virus (BDV), bovine viral diarrhea virus (BVDV), and classical swine fever virus (CSFV), were recognized in the pestivirus genus. These three species were defined by their host of origin, and to a lesser extent by clinical presentation. Subsequently, attempts ...
CLIL as a Way to Multilingualism
ERIC Educational Resources Information Center
Merino, Jon Ander; Lasagabaster, David
2018-01-01
Content and language integrated learning (CLIL) programmes are mushrooming in many different contexts. However, research has mainly focused on their impact on foreign language learning and to a lesser extent on L1 development, whereas the number of studies undertaken in multilingual contexts in which more than two languages coexist is negligible.…
Fraternity Membership & Frequent Drinking. NBER Working Paper No. 16291
ERIC Educational Resources Information Center
DeSimone, Jeffrey S.
2010-01-01
Reinforcing earlier findings from other data, college senior fraternity/sorority members are more likely to consume alcohol frequently. Large reductions in estimates upon controlling for time spent partying, and to a lesser extent cigarette use and intramural sports involvement, suggest considerable unobserved heterogeneity in the relationship.…
77 FR 44700 - Saratoga Investment Corp., et al.; Notice of Application
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-30
... lesser extent equity. The Investment Adviser, a Delaware limited liability company, is the investment..., a Delaware limited partnership, is a small business investment company (``SBIC'') licensed by the... Act. The Company directly owns 99% of Saratoga SBIC in the form of a limited partnership interest and...
USDA-ARS?s Scientific Manuscript database
Dates are a major food crop across a large band of Africa and Eurasia, and to a lesser extent elsewhere. In most of its growing range, dates are threatened with infestation in the field by a complex of pests including nitidulid beetles and pyralid moths of the Subfamily Phycitinae. They are further ...
Use of warm mix asphalt pavement along Rt. 27 in the towns of Farmington and New Portland.
DOT National Transportation Integrated Search
2012-05-01
A number of new technologies have been developed to lower the production and placement temperatures : of hot-mix asphalt (HMA). Generically, these technologies are referred to as warm-mix asphalt (WMA). : In Europe and to a lesser extent in North Ame...
EFFECTS OF DIETARY FOLATE ON ARSENIC-INDUCED GENE EXPRESSION IN MICE
Effects of Dietary Folate on Arsenic-induced Gene Expression in Mice
Arsenic, a drinking water contaminant, is a known carcinogen. Human exposure to inorganic arsenic has been linked to tumors of skin, bladder, lung, and to a lesser extent, kidney and liver. Dietary fola...
Environmental Influences on Reading-Related Outcomes: An Adoption Study
ERIC Educational Resources Information Center
Petrill, Stephen A.; Deater-Deckard, Kirby; Schatschneider, Christopher; Davis, Chayna
2007-01-01
Evidence from intervention studies, quantitative genetic and molecular genetic studies suggests that genetic, and to a lesser extent, shared environmental influences are important to the development of reading and related cognitive skills. The Northeast-Northwest Collaborative Adoption Projects (N2CAP) is a sample of 241 adoptive families,…
Jennifer Juzwik; Ji-Hyun Park; Linda Haugen
2014-01-01
Hickory decline, particularly decline in bitternut hickory (Carya cordiformis) and to a lesser extent in shagbark hickory (C. ovata), has recently been noted in Iowa, Maryland, Missouri, New York, Pennsylvania, West Virginia, and Wisconsin (Steinman 2004).
Linguistic Means of Expressing Distance between Interlocutors in Ukrainian.
ERIC Educational Resources Information Center
Bulatetska, Ludmila
Characteristics and patterns of Ukrainian language usage expressing social distance are analyzed, with examples given from current usage and, to a lesser extent, perspectives drawn from historical usage. It is concluded that Ukrainian has a rich morphological paradigm to express distance, primarily through diminutive morphology, which can…
J. Michael Scott; C. John Ralph
1981-01-01
Counting birds has a long tradition. Since early in human history, man has noted and recorded the presence, absence, and abundance of birds. This long, and presumably honorable, pursuit that we all engage in, to a greater or lesser extent, is the common currency of many ornithological studies. These studies range from multiple regression analyses of habitat variables...
The 1975 GSFC Battery Workshop
NASA Technical Reports Server (NTRS)
1975-01-01
The proceedings of the 1975 Goddard Space Flight Center Battery Workshop are presented. The major topics of discussion were nickel cadmium batteries and, to a lesser extent, nickel hydrogen batteries. Battery design, manufacturing techniques, testing programs, and electrochemical characteristics were considered. The utilization of these batteries for spacecraft power supplies was given particular attention.
The northern corn rootworm (Diabrotica barberi) and Mexican corn rootworm (Diabrotica virgifera zeae) are significant agricultural pests. For the northern corn rootworm, and to a lesser extent, the Mexican corn rootworm, high resolution molecular markers are needed. Here we pres...
Regional Assessment and Participative Evaluation: Final Report.
ERIC Educational Resources Information Center
Young, Roger L.; Gould, John A., Jr.
The report surveys the occupational environment of the towns in the region within 30 to 45 minutes' commuting time of North Reading, Massachusetts. A random sample of manufacturing, wholesale and retail trade, service, and to a much lesser extent finance, insurance, real estate establishments was surveyed in person or by mail. Information…
Investigation of Cool and Hot Executive Function in ODD/CD Independently of ADHD
ERIC Educational Resources Information Center
Hobson, Christopher W.; Scott, Stephen; Rubia, Katya
2011-01-01
Background: Children with oppositional defiant disorder/conduct disorder (ODD/CD) have shown deficits in "cool" abstract-cognitive, and "hot" reward-related executive function (EF) tasks. However, it is currently unclear to what extent ODD/CD is associated with neuropsychological deficits, independently of attention deficit hyperactivity disorder…
James, P J
1998-06-01
Of Moliere's thirty six plays, seven deal, to a greater or lesser extent, with medicine; the medicine as practiced in Paris during the reign of Louis XIV. In these days, Moliere satirises the recalcitrant conservatism of the Paris medical faculty. It is, however, an informed satirisation. This paper explores Moliere's motives and attempts to place Moliere's medical plays against a broad canvas of his other works. The ultimate purpose is to assess to what extent Moliere's philosophical persuasions and how he balanced them against the needs of contemporary, commercial theatre.
LECITHINASE AND LYSOLECITHINASE ACTIVITY OF RAT INTESTINAL MUCOSA AFTER WHOLE-BODY X-IRRADIATION
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ottolenghi, A.; Bernheim, F.
1961-11-01
Twenty-four hours after whole-body x irradiation the lecithinase activity of rat intestinal mucosa has markedly decreased and the lysolecithinase activity has decreasecp to a lesser extent. Addition of normal mucosa or chyi'otrypsin to the irradiated mucosa restores the activity of both enzymes. This indicates that irradiation eithei produces an inhibitor or inactivates a mechanism necessarly to convert pro-enzymes into active enzymes. Since chymo trypsin can increase to some extent the activity of the enzymes in normal mucosa, the second possibility seems more probable. (auth)
Thermal History Of PMRs Via Pyrolysis-Gas Chromatography
NASA Technical Reports Server (NTRS)
Gluyas, Richard E.; Alston, William B.; Snyder, William J.
1994-01-01
Pyrolysis-gas chromatography (PY-GC) useful as analytical technique to determine extents of cure or postcure of PMR-15 polyimides and to lesser extent, cumulative thermal histories of PMR-15 polyimides exposed to high temperatures. Also applicable for same purposes to other PMR polyimides and to composite materials containing PMR polyimides. Valuable in reducing costs and promoting safety in aircraft industry by helping to identify improperly cured or postcured PMR-15 composite engine and airframe components and helping to identify composite parts nearing ends of their useful lives.
Effects of bamboo biochar on soybean root nodulation in multi-elements contaminated soils.
Wang, Chunyan; Alidoust, Darioush; Yang, Xueling; Isoda, Akihiro
2018-04-15
Improvements in plant physiological performance by means of biochar application in soils contaminated by multi-elements are determinants of agroecosystem functioning. This study analyzed the effects of bamboo-derived biochar on root nodulation and plant growth in a moderately acidic Andosol (pH = 5.56) contaminated with multi-elements during a 70-day investigation of soybean growth. Bamboo biochar that had been pyrolyzed at a temperature below 500°C was applied to soils at three different and moderately high rates (5%, 10%, and 15%, w/w). Biochar amendment beyond 5% stimulated root nodulation as well as soybean growth. The nodule weight per root system was significantly enhanced by 186% and 243% over the control at the 10% and 15% addition rates, respectively. The primary explanation for these stimulatory effects was attributed to an increase in the K and Mo supplies for plant uptake that was induced by the biochar application, whereas the increased availability of P contributed to a lesser extent. Leaf CO 2 assimilation rate was slightly enhanced at the highest application rate, but this enhancement was not associated with an increase in biomass. The incorporation of biochar into the soil reduced extractable-NH 4 NO 3 Cd, Cu, Mn, Ni, and Zn, but not Pb, regardless of the application dose. This change was accompanied by a significant (P < 0.05) suppression of the uptake od trace elements in soybean shoots at the optimum application rate (10%); the degree of reduction followed this order: Pb>Mn>Cd>Zn>Cu>Ni. The increase in soil pH and the diffusion/adsorption of trace elements onto the biochar may have contributed to the lowering of the concentration of trace elements in the soil as well as in soybean shoots. Copyright © 2017 Elsevier Inc. All rights reserved.
Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice
Gray, Brian M.; Fontaine, Clinton A.; Poe, Sara A.
2013-01-01
Disease due to the gastric pathogen Helicobacter pylori varies in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model of H. pylori gastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that while H. pylori-specific CD4+ T cells and IFN-γ are both essential for induction of gastritis due to H. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due to H. pylori is associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway. PMID:23264048
Hernández, A J; Pastor, J
2008-04-01
Abandoned metal mines in the Sierra de Guadarrama, Madrid, Spain, are often located in areas of high ecological value. This is true of an abandoned barium mine situated in the heart of a bird sanctuary. Today the area sustains grasslands, interspersed with oakwood formations of Quercus ilex and heywood scrub (Retama sphaerocarpa L.), used by cattle, sheep and wild animals. Our study was designed to establish a relationship between the plant biodiversity of these grasslands and the bioavailability of heavy metals in the topsoil layer of this abandoned mine. We conducted soil chemical analyses and performed a greenhouse evaluation of the effects of different soil heavy metal concentrations on biodiversity. The greenhouse bioassays were run for 6 months using soil samples obtained from the mine polluted with heavy metals (Cu, Zn, Pb and Cd) and from a control pasture. Soil heavy metal and Na concentrations, along with the pH, had intense negative effects on plant biodiversity, as determined through changes in the Shannon index and species richness. Numbers of grasses, legumes, and composites were reduced, whilst other species (including ruderals) were affected to a lesser extent. Zinc had the greatest effect on biodiversity, followed by Cd and Cu. When we compared the sensitivity of the biodiversity indicators to the different metal content variables, pseudototal metal concentrations determined by X-ray fluorescence (XRF) were the most sensitive, followed by available and soluble metal contents. Worse correlations between biodiversity variables and metal variables were shown by pseudototal contents obtained by plasma emission spectroscopy (ICP-OES). Our results highlight the importance of using as many different indicators as possible to reliably assess the response shown by plants to heavy metal soil pollution.
Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong
2017-01-01
The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
From Foundation to Honours Degree: The Student Experience
ERIC Educational Resources Information Center
Greenbank, Paul
2007-01-01
Purpose: This paper aims to examine how students from foundation degrees (FDs) run at local further education colleges coped (academically and to a lesser extent psychologically) with the transition to a final year honours degree at a university. Design/methodology/approach: This paper is based on the experience of FD graduates who joined the…
"Go Boldly, Dream Large!": The Challenges Confronting Non-Traditional Students at University
ERIC Educational Resources Information Center
Munro, Lyle
2011-01-01
This article examines the challenges facing non-traditional university students--and to a lesser extent their lecturers in "the stretched academy"--who are increasingly enrolling in university courses in Australia and elsewhere. The article looks at this issue from the perspective of non-traditional students at a regional campus in…
Nonlinearity in Social Service Evaluation: A Primer on Agent-Based Modeling
ERIC Educational Resources Information Center
Israel, Nathaniel; Wolf-Branigin, Michael
2011-01-01
Measurement of nonlinearity in social service research and evaluation relies primarily on spatial analysis and, to a lesser extent, social network analysis. Recent advances in geographic methods and computing power, however, allow for the greater use of simulation methods. These advances now enable evaluators and researchers to simulate complex…
Uganda: Current Conditions and the Crisis in North Uganda
2010-05-19
constitution_1995. pdf . 5 John Kakande. “Museveni Speaks on 3rd Term.” The New Vision, January 3, 2003. 6 “President Should Listen to Old Friends...tea, and to a lesser extent, maize . Crop production has been hampered by security concerns in the northern and western regions of Uganda. To stabilize
USDA-ARS?s Scientific Manuscript database
Liriomyza huidobrensis is native to South America but has expanded its range and invaded many regions of the world, primarily on flowers and to a lesser extent on horticultural product shipments. As a result of initial invasion into an area, damage caused was usually significant but not necessarily...
SUMMARY REVIEW OF HEALTH EFFECTS ASSOCIATED WITH MERCURIC CHLORIDE: HEALTH ISSUE ASSESSMENT
Mercuric chloride (HgCl2) is a white crystalline substance that is currently used as a catalyst or reagent in various chemical reactions, and to a lesser extent as a disinfectant or pesticide. ercury exists in various valence states and forms (e.g., He, Hgo, Hg2 2+, and organic m...
Frequent Daytime Naps Predict Vocabulary Growth in Early Childhood
ERIC Educational Resources Information Center
Horváth, Klára; Plunkett, Kim
2016-01-01
Background: The facilitating role of sleep for language learning is well-attested in adults and to a lesser extent in infants and toddlers. However, the longitudinal relationship between sleep patterns and early vocabulary development is not well understood. Methods: This study investigates how measures of sleep are related to the development of…
Wound responses of wild apples suggest multiple resistance mechanism against blue mold decay
USDA-ARS?s Scientific Manuscript database
Blue mold caused primarily by Penicillium expansum and to a lesser extent other Penicillium spp. is the most destructive disease of stored apples in the US and worldwide. It was recently shown that resistance to blue mold exists in wild apple germplasms, Malus sieversii, from Kazakhstan and central...
Shimamune, Satoru; Smith, Stacey L.
1995-01-01
Two Japanese students were taught to pronounce and discriminate English words that contain unfamiliar phonemic contrasts (e.g., rock and lock). Teaching pronunciation was found to be easier than teaching listening discrimination. Teaching listening discrimination resulted in collateral improvement in pronunciation and, to a lesser extent, vice versa. PMID:16795883
Native bark beetles and wood borers in Mediterranean forests of California
Christopher J. Fettig
2016-01-01
Several species of bark beetles (Coleoptera: Curculionidae, Scolytinae), and to a much lesser extent wood borers (primarily Coleoptera: Buprestidae and Cerambycidae), are capable of causing conifer mortality in Mediterranean forests of California, U.S. This mortality is an important part of the ecology of these ecosystems, but the economic and social...
Understanding Genetics: Analysis of Secondary Students' Conceptual Status
ERIC Educational Resources Information Center
Tsui, Chi-Yan; Treagust, David F.
2007-01-01
This article explores the conceptual change of students in Grades 10 and 12 in three Australian senior high schools when the teachers included computer multimedia to a greater or lesser extent in their teaching of a genetics course. The study, underpinned by a multidimensional conceptual-change framework, used an interpretive approach and a…
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-11
... invest to a lesser extent in Money Market Securities and derivative instruments, as described below. \\10....S. government securities as U.S. government securities. Money Market Securities The Fund intends to invest in Money Market Securities (as described below) in a manner consistent with its investment...
Lessons Learned from Non-Marriage Experiments
ERIC Educational Resources Information Center
Schneider, Daniel
2015-01-01
In the contemporary United States, marriage is closely related to money. Men and (perhaps to a lesser extent) women with more education, higher incomes, larger stocks of wealth, and more stable employment are more likely to marry than are people in more precarious economic positions. But is this relationship truly causal? That is, does economic…
Post-Racial Pedagogy--Challenges and Possibilities
ERIC Educational Resources Information Center
Singh, Gurnam
2018-01-01
Against the backdrop of ongoing discussions about how best to conceptualise, confront and ultimately eradicate racism, this paper seeks to critically examine the relevance of 'post-racial' thinking, both in a general sense, but also in relation to education. The argument is framed around a concern that multi-cultural, and to a lesser extent,…
The Role and Effectiveness of Search Committees. AAHE-ERIC/Higher Education Research Currents.
ERIC Educational Resources Information Center
Bromert, Jane Doyle
1984-01-01
Perspectives concerning search committees for college faculty and administrators are considered. Most of the existing literature on college and university search committees deals with general presidential and, to a lesser extent, with administrative searches. Search committees are a fairly recent phenomenon in higher education, and their growth is…
ERIC Educational Resources Information Center
Ohler, Jason
2009-01-01
Being literate in a real-world sense means being able to read and write using the media forms of the day, whatever they may be. For centuries, consuming and producing words through reading and writing and, to a lesser extent, listening and speaking were sufficient. But because of inexpensive, easy-to-use, and widely available new tools, literacy…
ERIC Educational Resources Information Center
Hosch, Braden J.
2010-01-01
Using results from the Collegiate Learning Assessment (CLA) administered at Central Connecticut State University, a public Carnegie master's-larger programs university in the Northeast, this study demonstrates time on spent on the test, student motivation, and to a lesser extent the local institutional administration procedures represent…
I'll Do It Tomorrow: The Logic of Procrastination
ERIC Educational Resources Information Center
Zarick, Lisa M.; Stonebraker, Robert
2009-01-01
College students seem especially adept at procrastination. Large percents report that it causes lower quality papers and projects, lower exam scores and, to a lesser extent, late or missing assignments. Using survey data collected from a broad cross-section of students and faculty we argue that procrastination can be modeled as a logical, albeit…
Topsoil thickness effects on corn, soybean, and switchgrass production on claypan soils
USDA-ARS?s Scientific Manuscript database
Diminished topsoil thickness or depth to claypan (DTC) is a major cause of yield and profit depression in corn (Zea mays L.) and to a lesser extent in soybean (Glycine max [L.]) production on claypan soils. Perennial grasses such as switchgrass (Panicum virgatum L.) may be more resilient to reduced ...
Notions of "Rhetoric as Epistemic" in Ancient Greece.
ERIC Educational Resources Information Center
Benoit, William L.
The notion that rhetoric (and to a lesser extent, argument) is epistemic is an increasingly popular one today, although it can be traced to ancient Greece. The notion holds that rhetoric, or the art of persuasion, creates and shapes knowledge. Two ancient authors--Aristophanes and Plato--provide evidence that others had notions of rhetoric as…
The Impact of New Technology on the Accounting Curriculum.
ERIC Educational Resources Information Center
Shaoul, Jean
This paper analyzes ways in which the new, relatively cheap, user friendly technology and associated software is changing the way that accounting is being taught. Techniques that have been available, in principle, for years, are now widely available. The newer techniques stress decision making for planning, and, to a lesser extent, control, in…
Specification of High Activity Gamma-Ray Sources.
ERIC Educational Resources Information Center
International Commission on Radiation Units and Measurements, Washington, DC.
The report is concerned with making recommendations for the specifications of gamma ray sources, which relate to the quantity of radioactive material and the radiation emitted. Primary consideration is given to sources in teletherapy and to a lesser extent those used in industrial radiography and in irradiation units used in industry and research.…
Empirically Supported Family-Based Treatments for Conduct Disorder and Delinquency in Adolescents
ERIC Educational Resources Information Center
Henggeler, Scott W.; Sheidow, Ashli J.
2012-01-01
Several family-based treatments of conduct disorder and delinquency in adolescents have emerged as evidence-based and, in recent years, have been transported to more than 800 community practice settings. These models include multisystemic therapy, functional family therapy, multidimensional treatment foster care, and, to a lesser extent, brief…
Panoutsopoulos, Georgios I
2004-01-01
2-Phenylethylamine is an endogenous amine, which acts as a neuromodulator of dopaminergic responses. Exogenous 2-phenylethylamine is found in certain foodstuffs and may cause toxic side-effects in susceptible individuals. The present investigation examined the metabolism of 2-phenylethylamine to phenylacetic acid, via phenylacetaldehyde, in freshly prepared and cryopreserved liver slices. Additionally, it compared the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase by using specific inhibitors for each oxidizing enzyme. In freshly prepared and cryopreserved liver slices, phenylacetic acid was the main metabolite of 2-phenylethalamine. In freshly prepared liver slices, phenylacetic acid was completely inhibited by disulfiram (inhibitor of aldehyde dehydrogenase), whereas isovanillin (inhibitor of aldehyde oxidase) inhibited acid formation to a lesser extent and allopurinol (inhibitor of xanthine oxidase) had no effect. In cryopreserved liver slices, isovanillin inhibited phenylacetic acid by 85%, whereas disulfiram inhibited acid formation to a lesser extent and allopurinol had no effect. In liver slices, 2-phenylethylamine is rapidly oxidized to phenylacetic acid, via phenylacetaldehyde, by aldehyde dehydrogenase and aldehyde oxidase with no contribution from xanthine oxidase.
Numeracy skills of undergraduate entry level nurse, midwife and pharmacy students.
Arkell, Sharon; Rutter, Paul M
2012-07-01
The ability of healthcare professionals to perform basic numeracy and therefore dose calculations competently is without question. Research has primarily focused on nurses, and to a lesser extent doctors, ability to perform this function with findings highlighting poor aptitude. Studies involving pharmacists are few but findings are more positive than other healthcare staff. To determine first year nursing, midwifery and pharmacy students ability to perform basic numeracy calculations. All new undergraduate entrants to nursing, midwifery and pharmacy sat a formative numeracy test within the first two weeks of their first year of study. Test results showed that pharmacy students significantly outperformed midwifery and nursing students on all questions. In turn midwifery students outperformed nurses, although this did not achieve significance. When looking at each cohorts general attitude towards mathematics, pharmacy students were more positive and confident compared to midwifery and nursing students. Pharmacy students expressed greater levels of enjoyment and confidence in performing mathematics and correspondingly showed the greatest proficiency. In contrast nurse, and to a lesser extent midwifery students showed poor performance and low confidence levels. Copyright © 2012 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Wang, Peng; Wang, Yueming; Wu, Mingzai; Ye, Zhenhua
2018-06-01
Third-generation HgCdTe-based infrared focal plane arrays require high aspect ratio trenches with admissible etch induced damage at the surface and sidewalls for effectively isolating the pixels. In this paper, the high-density inductively coupled plasma enhanced reaction ion etching technique has been used for micro-mesa delineation of HgCdTe for third-generation infrared focal-plane array detectors. A nondestructive junction-level optoelectronic characterization method called laser beam induced current (LBIC) is used to evaluate the lateral junction extent of HgCdTe etch-induced damage scanning electron microscopy. It is found that the LBIC profiles exhibit evident double peaks and valleys phenomena. The lateral extent of etch induced mesa damage of ∼2.4 μm is obtained by comparing the LBIC profile and the scanning electron microscopy image of etched sample. This finding will guide us to nondestructively identify the distributions of the etching damages in large scale HgCdTe micro-mesa.
Díaz-Raviña, Montserrat; Bååth, Erland; Frostegård, Åsa
1994-01-01
A thymidine incorporation technique was used to determine the tolerance of a soil bacterial community to Cu, Cd, Zn, Ni, and Pb. An agricultural soil was artificially contaminated in our laboratory with individual metals at three different concentrations, and the results were compared with the results obtained by using the plate count technique. Thymidine incorporation was found to be a simple and rapid method for measuring tolerance. Data obtained by this technique were very reproducible. A linear relationship was found between changes in community tolerance levels obtained by the thymidine incorporation and plate count techniques (r = 0.732, P < 0.001). An increase in tolerance to the metal added to soil was observed for the bacterial community obtained from each polluted soil compared with the community obtained from unpolluted soil. The only exception was when Pb was added; no indication of Pb tolerance was found. An increase in the tolerance to metals other than the metal originally added to soil was also observed, indicating that there was multiple heavy metal tolerance at the community level. Thus, Cu pollution, in addition to increasing tolerance to Cu, also induced tolerance to Zn, Cd, and Ni. Zn and Cd pollution increased community tolerance to all five metals. Ni amendment increased tolerance to Ni the most but also increased community tolerance to Zn and, to lesser degrees, increased community tolerance to Pb and Cd. In soils polluted with Pb increased tolerance to other metals was found in the following order: Ni > Cd > Zn > Cu. We found significant positive relationships between changes in Cd, Zn, and Pb tolerance and, to a lesser degree, between changes in Pb and Ni tolerance when all metals and amendment levels were compared. The magnitude of the increase in heavy metal tolerance was found to be linearly related to the logarithm of the metal concentration added to the soil. Threshold tolerance concentrations were estimated from these linear relationships, and changes in tolerance could be detected at levels of soil contamination similar to those reported previously to result in changes in the phospholipid fatty acid pattern (Å. Frostegård, A. Tunlid, and E. Bååth, Appl. Environ. Microbiol. 59: 3605-3617, 1993). PMID:16349314
Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C
2003-10-01
The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.
Binding of human and rat CD59 to the terminal complement complexes.
Lehto, T; Morgan, B P; Meri, S
1997-01-01
CD59-antigen (protectin) is a widely distributed glycolipid-anchored inhibitor of complement lysis. CD59 interacts with complement components C8 and C9 during assembly of the membrane attack complex (MAC). To evaluate species specificity of these interactions we have in the present study examined cross-species binding of isolated human and rat CD59 to the terminal complement components C8 and C9. By using primarily soluble CD59 isolated from urine (CD59U) potentially non-specific binding interactions of the phospholipid portion of the membrane forms of CD59 could be avoided. Sucrose density gradient ultracentrifugation analysis showed that human CD59U bound to both human and rat C8 in the SC5b-8 complexes. Similar binding occurred when rat CD59U was used. The degree of binding did not significantly differ between the heterologous and homologous CD59-C8 combinations. C9 from both species inhibited the binding of CD59 to soluble SC5b-8. In ligand blotting analysis human and rat CD59U bound to human and rat C8 alpha gamma-subunit and C9. Binding of human and rat CD59U was stronger to human than rat C9. In plate binding assays the erythrocyte form of CD59 (CD59E) bound to both human and rat C8. Binding of CD59E to heterologous C9 was considerably weaker than to homologous C9. Our results imply that the reciprocal binding sites between C8 and CD59 and to a lesser degree between CD59 and C9 are conserved between human and rat. Interactions of CD59 with the terminal C components are thus species selective but not 'homologously restricted'. Images Figure 4 Figure 5 PMID:9038722
Uellendahl, Marly; de Siqueira, Maria Eduarda Menezes; Calado, Eveline Barros; Kalil-Filho, Roberto; Sobral, Dário; Ribeiro, Clébia; Oliveira, Wilson; Martins, Silvia; Narula, Jagat; Rochitte, Carlos Eduardo
2016-01-01
Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD. PMID:27982271
Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.
Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J
2018-05-25
Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Starch Characteristics Linked to Gluten-Free Products
Horstmann, Stefan W.; Lynch, Kieran M.; Arendt, Elke K.
2017-01-01
The increasing prevalence of coeliac disease (CD) and gluten-related disorders has led to increasing consumer demand for gluten-free products with quality characteristics similar to wheat bread. The replacement of gluten in cereal-based products remains a challenge for scientists, due to its unique role in network formation, which entraps air bubbles. When gluten is removed from a flour, starch is the main component left. Starch is used as gelling, thickening, adhesion, moisture-retention, stabilizing, film forming, texturizing and anti-staling ingredient. The extent of these properties varies depending on the starch source. The starches can additionally be modified increasing or decreasing certain properties of the starch, depending on the application. Starch plays an important role in the formulation of bakery products and has an even more important role in gluten-free products. In gluten-free products, starch is incorporated into the food formulation to improve baking characteristics such as the specific volume, colour and crumb structure and texture. This review covers a number of topics relating to starch; including; an overview of common and lesser researched starches; chemical composition; morphology; digestibility; functionality and methods of modification. The emphasis of this review is on starch and its properties with respect to the quality of gluten-free products. PMID:28383504
Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition.
Lesnikova, Iana; Schreckenbach, Marc Niclas; Kristensen, Maria Pihlmann; Papanikolaou, Liv Lindegaard; Hamilton-Dutoit, Stephen
2018-05-24
Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition.
Lee, Jessica A; Francis, Christopher A
2017-12-01
Denitrification is a dominant nitrogen loss process in the sediments of San Francisco Bay. In this study, we sought to understand the ecology of denitrifying bacteria by using next-generation sequencing (NGS) to survey the diversity of a denitrification functional gene, nirS (encoding cytchrome-cd 1 nitrite reductase), along the salinity gradient of San Francisco Bay over the course of a year. We compared our dataset to a library of nirS sequences obtained previously from the same samples by standard PCR cloning and Sanger sequencing, and showed that both methods similarly demonstrated geography, salinity and, to a lesser extent, nitrogen, to be strong determinants of community composition. Furthermore, the depth afforded by NGS enabled novel techniques for measuring the association between environment and community composition. We used Random Forests modelling to demonstrate that the site and salinity of a sample could be predicted from its nirS sequences, and to identify indicator taxa associated with those environmental characteristics. This work contributes significantly to our understanding of the distribution and dynamics of denitrifying communities in San Francisco Bay, and provides valuable tools for the further study of this key N-cycling guild in all estuarine systems. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.
Conservation Reserve Program mitigates grassland loss in the lesser prairie-chicken range of Kansas
Haukos, David A.; Spencer, David; Hagen, Christian A.; Daniels, Melinda D.; Goodin, Doug
2017-01-01
Since the beginning of the 20th century, the overall occupied range of the lesser prairie-chicken (Tympanuchus pallidicinctus) has declined by 84% commensurate with population trends. Much of this decline has been attributed to the loss and fragmentation of native grasslands throughout the lesser prairie-chicken range. However, quantification of changes in land cover in the distribution of the lesser prairie-chicken is lacking. Our objectives were to (1) document changes in the areal extent and connectivity of grasslands in the identified lesser prairie-chicken range in Kansas, USA, (>60% of extant lesser prairie-chicken population) from the 1950s to 2013 using remotely sensed data and (2) assess the potential of the Conservation Reserve Program (U.S. Department of Agriculture Program converting cropland to permanent cover; CRP) to mitigate grassland loss. Digital land cover maps were generated on a decadal time step through spectral classification of LANDSAT images and visual analysis of aerial photographs (1950s and 1960s). Landscape composition and configuration were assessed using FRAGSTATS to compute a variety of landscape metrics measuring changes in the amount of grassland present as well as changes in the size and configuration of grassland patches. With the exception of a single regional portion of the range, nearly all of the grassland converted to cropland in the lesser prairie-chicken range of Kansas occurred prior to the 1950s. Prior to the implementation of CRP, the amount of grassland decreased 3.6% between the 1950s and 1985 from 18,455 km2 to 17,788 km2. Since 1985, the overall amount of grassland in the lesser prairie-chicken range has increased 11.9% to 19,898 km2 due to implementation of CRP, although the area of grassland decreased between 1994 and 2013 as CRP contracts were not renewed by landowners. Since 1986 grassland in Kansas became more connected and less fragmented in response to the CRP. While the CRP has been successful in increasing grassland quantity and connectivity throughout the lesser prairie-chicken range in Kansas, offsetting loss of grassland since the 1950s, abundance and occupied range of lesser prairie-chickens has declined since the 1980s, suggesting that habitat quality is the principal factor influencing population demography of the species. Although the CRP is contributing to conservation actions for lesser prairie-chickens, efforts to improve habitat quality throughout the range of the lesser prairie-chicken are likely necessary to meet management goals. Continuation of the CRP faces an uncertain future in the face of rising commodity prices, energy development, and reduction in program scope, leaving open the possibility that these areas that have created habitat for lesser prairie-chickens could be lost.
Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C
2015-08-01
We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.
An Exploratory Study Contrasting High- and Low-Achieving Students' Percent Word Problem Solving
ERIC Educational Resources Information Center
Jitendra, Asha K.; Star, Jon R.
2012-01-01
This study evaluated whether schema-based instruction (SBI), a promising method for teaching students to represent and solve mathematical word problems, impacted the learning of percent word problems. Of particular interest was the extent that SBI improved high- and low-achieving students' learning and to a lesser degree on the indirect effect of…
Re Thinking the Public Sector Role in Training: A B.C. College's Response.
ERIC Educational Resources Information Center
Witter, Susan
Prior to 1985, the British Columbia (Canada) community colleges relied heavily on institutional seat purchases (direct funding) to support ongoing vocational programs and, to a lesser extent, to implement new training programs. With the introduction of the Canada Job Strategy in 1985, many of the seat purchases were reduced in favor of indirect…
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-08
.... Simplot, a phosphate fertilizer manufacturing facility which is 86 km from Craters of the Moon National... any type is primarily due to emissions of organic carbon and elemental carbon, and to a lesser extent... organic carbon emissions in 2018 from natural fires compared to 4,100 tons from anthropogenic fires. With...
The Education and Training of Physics Teachers Worldwide. A Survey.
ERIC Educational Resources Information Center
Davies, Brian, Ed.
The Group Internationale de Recherche sur l'Enseignment de la Physique (GIREP), known in English as The International Research Group on Physics Teaching, is an independent association for the improvement of physics teaching in schools and, to a lesser extent, at the interface between school and university. Provided in this three-part book is…
The Personal and Professional Selves of Teachers: Stable and Unstable Identities
ERIC Educational Resources Information Center
Day, Christopher; Kington, Alison; Stobart, Gordon; Sammons, Pam
2006-01-01
In much educational literature it is recognised that the broader social conditions in which teachers live and work, and the personal and professional elements of teachers' lives, experiences, beliefs and practices are integral to one another, and that there are often tensions between these which impact to a greater or lesser extent upon teachers'…
Detection of Emotional Faces: Salient Physical Features Guide Effective Visual Search
ERIC Educational Resources Information Center
Calvo, Manuel G.; Nummenmaa, Lauri
2008-01-01
In this study, the authors investigated how salient visual features capture attention and facilitate detection of emotional facial expressions. In a visual search task, a target emotional face (happy, disgusted, fearful, angry, sad, or surprised) was presented in an array of neutral faces. Faster detection of happy and, to a lesser extent,…
The Internet & Regional Australia: How Rural Communities Can Address the Impact of the Internet.
ERIC Educational Resources Information Center
Simpson, Rosie
In the last decade, a technological revolution has touched all aspects of business and society in Australia, the Western world, and to a lesser extent, the developing world. This revolution has occurred against a backdrop of long-term fundamental changes in rural Australian communities. The decline in traditional agriculture's terms of trade and…
ERIC Educational Resources Information Center
Heinz, Manuela; Davison, Kevin; Keane, Elaine
2018-01-01
There has been extensive research internationally describing teachers' homogenous socio-demographic backgrounds and critiquing the associated equity and diversity issues, most especially with regard to ethnicity and gender, and to a lesser extent, social class and disability. Yet, teachers' religious affiliations and/or convictions have rarely…
Inclusive School Is (Not) Possible--Pupil's Voice
ERIC Educational Resources Information Center
Pavlovic, Slavica
2016-01-01
Inclusive education has been the focus of a number of research studies in Bosnia and Herzegovina. However, most of the research was based on the teachers and to a lesser extent on parents' attitudes towards inclusive education, while pupils' views and voice were mainly neglected. The core of this paper is survey research on primary school pupils'…
Lithium Ion Vehicle Start Batteries - Power for the Future
2011-08-09
results in less power being available as the battery state of charge (and voltage) is decreased. Lithium Nanophosphate ( LiFePO4 ) exhibits this to...a much lesser extent. As shown in figure 1, the voltage v. SOC curve for LiFePO4 is nearly flat throughout most of its state of charge.[1] This
Meeting the Needs of Students in Recovery. Prevention Update
ERIC Educational Resources Information Center
Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2010
2010-01-01
In its 2002 report on college drinking, the National Institute on Alcohol Abuse and Alcoholism describes U.S. college campuses as supporting a culture of drinking. Staying clean and sober in an environment where drinking and, to a lesser extent, other drug use is an accepted behavior presents real challenges to students who are in recovery from…
The Fragile X Continuum: New Advances and Perspectives
ERIC Educational Resources Information Center
Cornish, K.; Turk, J.; Hagerman, R.
2008-01-01
Fragile X syndrome is the world's most common hereditary cause of intellectual disability in men and to a lesser extent in women. The disorder is caused by the silencing of a single gene on the X chromosome, the Fragile X Mental Retardation Gene-1. A substantial body of research across the disciplines of molecular genetics, child psychiatry and…
A need to define characteristics to be used in the taxonomy of the expanding pestivirus genus
USDA-ARS?s Scientific Manuscript database
The relatively high rate of genetic drift observed with pestiviruses results not only in the emergence of new species but also in heterogeneity within recognized species. The grouping of pestiviruses into species was first based on host and to a lesser extent clinical presentation, then later by an...
Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotrop...
System in Black Language. Multilingual Matters Series: 77.
ERIC Educational Resources Information Center
Sutcliffe, David; Figueroa, John
An examination of pattern in certain languages spoken primarily by Blacks has both a narrow and a broad focus. The former is on structure and development of the creole spoken by Jamaicans in England and to a lesser extent, a Black country English. The broader focus is on the relationship between the Kwa languages of West Africa and the…
Aspen: Ecology and management in the western United States
Norbert V. DeByle; Robert P. Winokur
1985-01-01
Information about the biology, ecology, and management of quaking aspen on the mountains and plateaus of the interior western United States, and to a lesser extent, Canada, is summarized and discussed. The biology of aspen as a tree species, community relationships in the aspen ecosystem, environments, and factors affecting aspen forests are reviewed. The resources...
A Critical Review of ADHD Diagnostic Criteria: What to Address in the "DSM-V"
ERIC Educational Resources Information Center
Bell, Allison S.
2011-01-01
ADHD is an impairing psychological disorder that predominantly affects children, but also adults to a lesser extent. As a result, a considerable amount of research has been completed in recent years to better understand the nature of the disorder to best treat individuals experiencing symptoms of ADHD. Especially with the publication of the…
Effect of precooking and polyphosphate treatment on the quality of microwave cooked catfish fillets
USDA-ARS?s Scientific Manuscript database
In the US market place there are many examples of precooked poultry products designed to be reheated in a microwave oven and, to a lesser extent, fish products such as tilapia. However, few US catfish products are designed to be microwave cooked or reheated. The first objective of this study was t...
L2 Effects on L1 Event Conceptualization
ERIC Educational Resources Information Center
Bylund, Emanuel; Jarvis, Scott
2011-01-01
The finding that speakers of aspect languages encode event endpoints to a lesser extent than do speakers of non-aspect languages has led to the hypothesis that there is a relationship between grammatical aspect and event conceptualization (e.g., von Stutterheim and Nuse, 2003). The present study concerns L1 event conceptualization in 40 L1…
ERIC Educational Resources Information Center
Benito, Ricard; Alegre, Miquel Àngel; Gonzàlez-Balletbò, Isaac
2014-01-01
Using PISA data for 16 Western OECD countries having comprehensive school systems, we explore the conditions under which the socioeconomic composition of schools affects educational efficiency and equality, to a greater or lesser extent. First, a multilevel analysis is applied to examine and compare the effect of school socioeconomic composition…
ERIC Educational Resources Information Center
Fischer, Britta; Bisterfeld, Miriam; Staab, Oliver
2018-01-01
To a greater or lesser extent, specific combinations of commitment, resilience and subjective well-being represent favorable individual resources in order to cope with professional demands. Prior studies have identified different patterns of these behaviors and experiences. The present study deals with the question whether these patterns are also…
To measure airborne asbestos and other fibers, an air sample must represent the actual number and size of fibers. Typically, mixed cellulose ester (MCE, 0.45 or 0.8 µm pore size) and to a much lesser extent, capillary-pore polycarbonate (PC, 0.4 µm pore size) membrane filters are...
ERIC Educational Resources Information Center
Stanley, Elizabeth C.; Patrick, William J.
Two important sets of performance indicators for institutions of higher education have become established in the United Kingdom: research quality ratings and teaching quality ratings. The research quality ratings and, to a lesser extent, the teaching quality ratings influence the level of government funding provided to higher education…
Biomechanically Preferred Consonant-Vowel Combinations Fail to Appear in Adult Spoken Corpora
ERIC Educational Resources Information Center
Whalen, D. H.; Giulivi, Sara; Nam, Hosung; Levitt, Andrea G.; Halle, Pierre; Goldstein, Louis M.
2012-01-01
Certain consonant/vowel (CV) combinations are more frequent than would be expected from the individual C and V frequencies alone, both in babbling and, to a lesser extent, in adult language, based on dictionary counts: Labial consonants co-occur with central vowels more often than chance would dictate; coronals co-occur with front vowels, and…
Dominant Language Transfer in Adult Second Language Learners and Heritage Speakers
ERIC Educational Resources Information Center
Montrul, Silvina
2010-01-01
The effects of language transfer have been amply documented in second language (L2) acquisition and, to a lesser extent, in the language contact/loss literature (Cook, 2003). In both cases, the stronger and often dominant language encroaches into the structure of the less dominant language in systematic ways. But are transfer effects in these two…
SOME INSIGHTS INTO THE MODE OF ACTION OF BUTADIENE BY EXAMINING THE GENOTOXICITY OF ITS METABOLITES
1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action...
ERIC Educational Resources Information Center
Barker, Edward D.; Salekin, Randall T.
2012-01-01
Background: Irritability is a subdimension of ODD, which predicts mainly to internalizing disorders, and to a lesser extent, conduct problems and callous-unemotional traits. Given that youth with similar dispositions as the irritable types--as well as youth high in callous-unemotional (CU) traits--have both been reported to experience high levels…
Bayoxide® E33 (E-33, Goethite) is a widely used commercial material for arsenic adsorption. It is a mixture of iron oxyhydroxide and oxides. E-33 is primarily used to remove arsenic from water and to a lesser extent, other anions, but generally lacks multifunctuality. It is a non...
Spatial distribution of Cd and Cu in soils in Shenyang Zhangshi Irrigation Area (SZIA), China*
Sun, Li-na; Yang, Xiao-bo; Wang, Wen-qing; Ma, Li; Chen, Su
2008-01-01
Heavy metal contamination of soils, derived from sewage irrigation, mining and inappropriate utilization of various agrochemicals and pesticides, and so on, has been of wide concern in the last several decades. The Shenyang Zhangshi Irrigation Area (SZIA) in China is a representative area of heavy metal contamination of soils resulting from sewage irrigation for about 30 years. This study investigated the spatial distribution and temporal variation of soil cadmium (Cd) and copper (Cu) contamination in the SZIA. The soil samples were collected from the SZIA in 1990 and 2004; Cd and Cu in soils was analyzed and then the spatial distribution and temporal variation of Cd and Cu in soils were modeled using Kriging methods. The results show that long-term sewage irrigation had caused serious Cd and Cu contamination in soils. The mean and the maximum of soil Cd are markedly higher than the levels in second grade standard soil (LSGSS) in China, and the maximum of soil Cu is close to the LSGSS in China in 2004 and is more than the LSGSS in China in 1990. The contamination magnitude of soil Cd and the soil extent of Cd contamination had evidently increased since sewage irrigation ceased in 1992. The contamination magnitude of soil Cu and the soil extent of Cu contamination had evidently increased in topsoil, but obviously decresed in subsoil. The soil contamination of Cd and Cu was mainly related to Cd and Cu reactivation of contaminated sediments in Shenyang Xi River and the import of Cd and Cu during irrigation. The eluviation of Cd and Cu in contaminated topsoil with rainfall and irrigation water was another factor of temporal-spatial variability of Cd and Cu contamination in soils. PMID:18357631
NASA Astrophysics Data System (ADS)
Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.
1996-11-01
Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.
Stadlmann, Valerie; Harant, Hanna; Korschineck, Irina; Hermann, Marcela; Forster, Florian; Missbichler, Albert
2015-12-01
Celiac disease (CD) is a chronic, small intestinal inflammatory disease mediated by dietary gluten and related prolamins. The only current therapeutic option is maintenance of a strict life-long gluten-free diet, which implies substantial burden for CD patients. Different treatment regimes might be feasible, including masking of toxic celiac peptides with blocking antibodies or fragments thereof. The objective of this study was therefore to select and produce a recombinant avian single-chain fragment variable (scFv) directed against peptic-tryptic digested gliadin (PT-Gliadin) and related celiac toxic entities. Gluten-free raised chicken of same age were immunized with PT-Gliadin. Chicken splenic lymphocytes, selected with antigen-coated magnetic beads, served as RNA source for the generation of cDNA. Chicken VH and VL genes were amplified from the cDNA by PCR to generate full-length scFv constructs consisting of VH and VL fragments joined by a linker sequence. ScFv constructs were ligated in a prokaryotic expression vector, which provides a C-terminal hexahistidine tag. ScFvs from several bacterial clones were expressed in soluble form and crude cell lysates screened for binding to PT-Gliadin by ELISA. We identified an enriched scFv motif, which showed reactivity to PT-Gliadin. One selected scFv candidate was expressed and purified to homogeneity. Polyclonal anti-PT-Gliadin IgY, purified from egg yolk of immunized chicken, served as control. ScFv binds in a dose-dependent manner to PT-Gliadin, comparable to IgY. Furthermore, IgY competitively displaces scFv from PT-Gliadin and natural wheat flour digest, indicating a common epitope of scFv and IgY. ScFv was tested for reactivity to different gastric digested dietary grain flours. ScFv detects common and khorasan wheat comparably with binding affinities in the high nanomolar range, while rye is detected to a lesser extent. Notably, barley and cereals which are part of the gluten-free diet, like corn and rice, are not detected by scFv. Similarly, the pseudo-grain amaranth, used as gluten-free alternative, is not targeted by scFv. This data indicate that scFv specifically recognizes toxic cereal peptides relevant in CD. ScFv can be of benefit for future CD treatment regimes.
Hadley, David; Hagopian, William; Liu, Edwin; She, Jin-Xiong; Simell, Olli; Akolkar, Beena; Ziegler, Anette-G; Rewers, Marian; Krischer, Jeffrey P; Chen, Wei-Min; Onengut-Gumuscu, Suna; Bugawan, Teodorica L; Rich, Stephen S; Erlich, Henry; Agardh, Daniel
2015-06-01
Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. After adjustment for DR3-DQ2 and restriction to allele frequency (AF) ≥5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). HLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.
Saikia, Jyotilima; Narzary, Bardwi; Roy, Sonali; Bordoloi, Manobjyoti; Saikia, Prasenjit; Saikia, Binoy K
2016-12-01
Studies on coal-derived nanoparticles as well as nano-minerals are important in the context of the human health and the environment. The coal combustion-generated aerosols also affect human health and environmental quality aspects in any coal-fired station. In this study, the feed coals and their combustion-generated aerosols from coal-fired boilers of two tea industry facilities were investigated for the presence of nanoparticles/nano minerals, fullerene aggregates, and potentially hazardous elements (PHEs). The samples were characterized by using X-ray diffraction (XRD), Time-of-flight secondary ion mass spectroscopy (TOF-SIMS), High resolution-transmission electron microscopy/energy dispersive spectroscopy (HR-TEM/EDS) and Ultra Violet-visible spectroscopy (UV-Vis) to know their extent of environmental risks to the human health when present in coals and aerosols. The feed coals contain mainly clay minerals, whilst glass fragments, spinel, quartz, and other minerals occur in lesser quantities. The PM samples contain potentially hazardous elements (PHEs) like As, Pb, Cd and Hg. Enrichment factor of the trace elements in particulate matters (PMs) was calculated to determine their sources. The aerosol samples were also found to contain nanomaterials and ultrafine particles. The fullerene aggregates along with potentially hazardous elements were also detected in the aerosol samples. The cytotoxicity studies on the coal combustion-generated PM samples show their potential risk to the human health. This detailed investigation on the inter-relationship between the feed coals and their aerosol chemistry will be useful for understanding the extent of environmental hazards and related human health risk. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Yu, Qiang; Fein, Jeremy B.
2015-10-01
The adsorption and desorption of Cd onto Shewanella oneidensis bacterial cells with and without blocking of sulfhydryl sites was measured in order to determine the effect of metal loading and to understand the role of sulfhydryl sites in the adsorption reactions. The observed adsorption/desorption behaviors display strong dependence on metal loading. Under a high loading of 40 μmol Cd/g bacterial cells, blocking the sulfhydryl sites within the cell envelope by exposure of the biomass to monobromo(trimethylammonio)bimane bromide (qBBr) does not significantly affect the extent of Cd adsorption, and we observed fully reversible adsorption under this condition. In contrast, under a low metal loading of 1.3 μmol Cd/g bacterial cells, the extent of Cd adsorption onto sulfhydryl-blocked S. oneidensis cells was significantly lower than that onto untreated cells, and only approximately 50-60% of the adsorbed Cd desorbed from the cells upon acidification. In conjunction with previous EXAFS results, our findings demonstrate that Cd adsorption onto S. oneidensis under low metal loading conditions is dominated by sulfhydryl binding, and thus is controlled by a distinct adsorption mechanism from the non-sulfhydryl site binding which controls Cd adsorption under high metal loading conditions. We use the data to develop a surface complexation model that constrains the values of the stability constants for individual Cd-sulfhydryl and Cd-non-sulfhydryl bacterial complexes, and we use this approach to account for the Cd adsorption behavior as a function of both pH and metal loading. This approach is crucial in order to predict metal adsorption onto bacteria under environmentally relevant metal loading conditions where sulfhydryl binding sites can dominate the adsorption reaction.
Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.
Almeida, Julia; Polvorosa, Maria Angeles; Gonzalez-Quintela, Arturo; Madruga, Ignacio; Marcos, Miguel; Pérez-Nieto, Maria Angeles; Hernandez-Cerceño, Maria Luisa; Orfao, Alberto; Laso, Francisco Javier
2015-08-01
Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells. Copyright © 2015 by the Research Society on Alcoholism.
Knoll, Rebecca L; Forslund, Kristoffer; Kultima, Jens Roat; Meyer, Claudius U; Kullmer, Ulrike; Sunagawa, Shinichi; Bork, Peer; Gehring, Stephan
2017-04-01
Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD. Copyright © 2017 the American Physiological Society.
Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema
Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham
2017-01-01
Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826
Grazing in central hardwood forests
Robert A. McQuilkin; Harold Scholten
1989-01-01
Woodland grazing is a major forestry and land management problem in parts of the central hardwood region. Most forest grazing is by cattle and, to a lesser extent, hogs in woodlands adjacent to pastures or feedlots. The practice is particularly common in the cattle producing areas of the Corn Belt where often 50 percent or more of the upland forest is grazed. Woodland...
ERIC Educational Resources Information Center
Laubach, Thomas
2005-01-01
This paper discusses the current state of fiscal relations between the federal, state and local governments in the United States and suggests directions for improvement. The significant degree of fiscal autonomy of the states and, to a lesser extent, of local governments has had several beneficial effects, including the responsiveness of public…
ERIC Educational Resources Information Center
Hardaker, Glenn; Sabki, Aishah; Qazi, Atika; Iqbal, Javed
2017-01-01
Purpose: Most research on information and communication technologies (ICT) differences has been related to gender and ethnicity, and to a lesser extent religious affiliation. The purpose of this paper is to contribute to this field of research by situating the discussion in the context of British Muslims and extending current research into ICT…
ERIC Educational Resources Information Center
Heinz, Manuela; Keane, Elaine; Davison, Kevin
2017-01-01
While research and policy recommendations internationally have pointed to the need to diversify teaching populations with regard to ethnicity, social class background and, to a lesser extent, dis/ability, there is a paucity of research addressing sexualities as a diversity dimension in teaching. This article explores initial teacher education…
The Use of Song to Open an Educational Development Workshop: Exploratory Analysis and Reflections
ERIC Educational Resources Information Center
Lesser, Lawrence; An, Song; Tillman, Daniel
2016-01-01
Song has been used by faculty of many disciplines in their classrooms and, to a lesser extent, by educational developers in workshops. This paper shares and discusses a new song (about an instructor's evolving openness to alternatives to lecture-only teaching) and its novel use to open an educational development workshop. Self-reported participant…
Jean-David Moore; Rock Ouimet; Robert P. Long; Paul. A. Bukaveckas
2015-01-01
Liming, the application of carbonate materials (e.g., CaCO3, CaMg(CO3)2) to soils and surface waters, has been used extensively in Europe, and to a lesser extent in Canada and the United States, to mitigate the effects of acid deposition on forest and aquatic ecosystems. This literature review was...
Multicultural and Popular Music Content in an American Music Teacher Education Program
ERIC Educational Resources Information Center
Wang, Jui-Ching; Humphreys, Jere T.
2009-01-01
The teaching of multicultural music, and to a lesser extent popular music, has been the stated goal of music education policy makers for many decades. Accordingly, the purpose of this study was to estimate the amount and percentage of time music education majors in a university teacher education program spent on 13 styles of music in history,…
USDA-ARS?s Scientific Manuscript database
Fusarium species are frequently associated with mycotic keratitis and, to a lesser extent, cases of localized and disseminated infections. The Fusarium solani species complex (FSSC) is the most common group of fusaria associated with human infectious diseases. Several studies to date have revealed d...
Woodall publishing company, an important industry source of camping information
Curtis Fuller; Paul Foght; Linda Profaizer
1980-01-01
Since 1967 the Woodall Publishing Company of Highland Park, Ill., has gathered annual statistics on privately owned campgrounds in the United States, Canada and Mexico and to a lesser extent on public campgrounds. At first the information gathered consisted of little more than hand tallies of the number of campgrounds by state and degree of development, of the number...
Toward improving our application and understanding of crown fire behavior
Martin E. Alexander; Miguel G. Cruz; Nicole M. Vaillant
2014-01-01
The suggestion has been made that most wildland fire operations personnel base their expectations of how a fire will behave largely on experience and, to a lesser extent, on guides to predicting fire behavior (Burrows 1984). Experienced judgment is certainly needed in any assessment of wildland fire potential but it does have its limitations. The same can be said for...
ERIC Educational Resources Information Center
Colorado State Advisory Committee to the U.S. Commission on Civil Rights, Denver.
Based on background research, interviews, and a public hearing held in Durango (Colorado) in March 1993, this report addresses issues regarding minority retention at Fort Lewis College in Durango and, to a lesser extent, at Adams State College in Alamosa. Due to limited information about Adams State College, none of the recommendations address…
ERIC Educational Resources Information Center
Blair, Clancy; Granger, Douglas A.; Willoughby, Michael; Mills-Koonce, Roger; Cox, Martha; Greenberg, Mark T.; Kivlighan, Katie T.; Fortunato, Christine K.
2011-01-01
In a predominantly low-income population-based longitudinal sample of 1,292 children followed from birth, higher level of salivary cortisol assessed at ages 7, 15, and 24 months was uniquely associated with lower executive function ability and to a lesser extent IQ at age 3 years. Measures of positive and negative aspects of parenting and…
Effect of Pre-cooking and Addition of Phosphate on the Quality of Microwave Cooked Catfish Fillets
USDA-ARS?s Scientific Manuscript database
In the US market place there are many examples of precooked poultry products designed to be reheated in a microwave oven and to a lesser extent fish products such as tilapia. However, there are few US catfish products designed to be microwave cooked or reheated in the market place. The first objecti...
A Class Act--Mathematics as Filter of Equity in South Africa's schools
ERIC Educational Resources Information Center
Kahn, Michael
2005-01-01
This article explores the way that educational disadvantage and opportunity became manifest in the South African school system by tracking performance in the gateway subject of Mathematics (and to a lesser extent Physical Science). Previous research by the author showed how it was possible to use a proxy method to track redress in the absence of…
Young Norwegian-Pakistani Women and Sport: How Does Culture and Religiosity Matter?
ERIC Educational Resources Information Center
Walseth, Kristin; Strandbu, Åse
2014-01-01
Studies from several countries show that girls with an immigrant background participate in organized sports to a lesser extent than other young people. Barriers related to culture and religion serve in many of these studies as explanations. In this article we suggest that the notions of culture and religion in this field of studies could be…
El Salvador: Background and U.S. Relations
2017-03-08
money laundering ; and drug, auto, and weapons smuggling. Gangs earn millions of dollars by extorting residents, bus drivers, and business owners...allegedly laundered the gang’s money through motels, brothels, and other businesses.20 Drug-trafficking organizations, including Mexican groups such as...the Sinaloa criminal organization, have increased their illicit activities in El Salvador, including money laundering , albeit to a lesser extent than
Teaching Mathematics and Astronomy in France: The "College Royal" (1550-1650)
ERIC Educational Resources Information Center
Pantin, Isabelle
2006-01-01
For a long time, the medieval university maintained relative consistency throughout Europe in teaching topics and methods. But between 1550 and 1650 this came to an end. The evolution concerned the content of the courses and, to a lesser extent, the way the field was taught. The impact of these changes varied greatly from place to place, and new…
The Development of the Humanistic Curriculum in Fifteenth-Century Italy.
ERIC Educational Resources Information Center
Grendler, Paul F.
One of the major changes in educational practices occurred during the Italian Renaissance, when a system of pre-university education based on a thorough grounding in the Latin, and to a lesser extent, the Greek classics began. This change started in early 15th century northern Italy and lasted until well into the 20th century. Italian school…
NASA Astrophysics Data System (ADS)
Zbucki, Łukasz
2012-12-01
Southern Podlasie Lowland seems to be poor in geoturistic facilities. The conducted research on the geoturistic activity of the lowland inhabitants has indicated that the education is the determining factor. The age and place of residence seem to affect the geoturistic activity to a lesser extent
Legume ground covers alter defoliation response of black walnut saplings to drought and anthracnose
J. W. Van Sambeek
2003-01-01
Growth and premature defoliation of black walnut saplings underplanted 5 or 6 years earlier with six different ground covers were quantified in response to a summer drought or anthracnose. Walnut saplings growing with ground covers of hairy vetch, crownvetch, and to a lesser extent sericea lespedeza continued to have more rapid height and diameter growth than saplings...
ERIC Educational Resources Information Center
Burgos-Sasscer, Ruth
Effective management of human resources in any organization includes providing an environment that is conducive to the satisfaction of basic needs in the workplace. This concept has been increasingly embraced by business and industry and to a lesser extent in academia. One group considered vital to higher education, whose needs have been ignored,…
Drug Traffic and Abuse in Schools: NSSC Resource Paper.
ERIC Educational Resources Information Center
National School Safety Center, Sacramento, CA.
Drug abuse in schools, and to a lesser extent, alcohol and tobacco abuse, are the topics of this report. Discussions are provided in these areas: (1) prevalence of drug abuse; (2) student attitudes and beliefs; (3) drug laws and school rules; (4) student searches and drug testing; (5) drug epidemic reaching the very young; (6) tobacco abuse; (7)…
Akinboro, Adeolu Oladayo; Onayemi, Olaniyi; Mejiuni, Ayodele D
2014-04-01
Skin diseases characterize all stages of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and contribute significantly to associated morbidity and mortality. The aim of this study was to document the prevalences, patterns, and extents (severity) of skin diseases and their relationships with immunologic status in HIV/AIDS patients. A total of 140 HIV/AIDS patients in different stages of HIV infection and 140 controls were recruited. Skin diseases were documented and CD4+ cell counts determined in all subjects. Severity was assessed according to the body surface area affected (using the Wallace rule of nines and the rule of palm) for lesions that tended to be widespread. The number of digits involved was counted for lesions involving the nails. Intensity of pain was graded for specific conditions such as herpes zoster. Chi-squared statistics and Pearson correlations were determined. Mean±standard deviation age was 35.04±8.83 years in the patient group and 32.21±8.30 years in the control group. The prevalences and patterns of skin diseases in HIV/AIDS patients were similar to those reported in previous studies. Most commonly found dermatoses were oral candidiasis (n=28, 20.0%), pruritic papular eruption (n=27, 19.3%), xeroderma (n=23, 16.4%), dermatophytosis (n=22, 15.7%), and fluffy hair (n=19, 13.6%). The presence of specific skin lesions represented a better correlate with immunosuppression than cutaneous extents. However, the extents of viral warts and multiple blue–black nails correlated significantly with CD4+ cell count. The presence of a lighter hair color phenotype signifies a lower CD4+ cell count than a softer hair phenotype. The presence of specific skin lesions correlates more strongly with a low CD4+ cell count than does the extent of their distribution, except in cases of viral warts. The presence of and higher numbers of nails affected with blue–black nail hyperpigmentation suggest severe immunosuppression.
[Hypoxia and memory. Specific features of nootropic agents effects and their use].
Voronina, T A
2000-01-01
Hypoxia and hypoxic adaptation are powerful factors of controlling memory and behavior processes. Acute hypoxia exerts a differential impact on different deficits of mnestic and cognitive functions. Instrumental reflexes of active and passive avoidance, negative learning, behavior with a change in the stereotype of learning are more greatly damaged. Memory with spatial and visual differentiation and their rearrangement change to a lesser extent and conditional reflexes are not deranged. In this contract, altitude hypoxic adaptation enhances information fixation and increases the degree and duration of retention of temporary relations. Nootropic agents with an antihypoxic action exert a marked effect on hypoxia-induced cognitive and memory disorders and the magnitude of this effect depends on the ration of proper nootropic to antihypoxic components in the spectrum of the drugs' pharmacological activity. The agents that combine a prevailing antiamnestic effect and a marked and moderate antihypoxic action (mexidole, nooglutil, pyracetam, beglymin, etc.) are most effective in eliminating different hypoxia-induced cognitive and memory disorders, nootropic drugs that have a pronounced antiamnestic activity (centrophenoxine, etc.) and no antihypoxic component also restore the main types of mnestic disorders after hypoxia, but to a lesser extent.
Freire, Rosemayre S; Morais, Selene M; Catunda-Junior, Francisco Eduardo A; Pinheiro, Diana C S N
2005-07-01
Some derivatives of trans-anethole [1-methoxy-4-(1-propenyl)-benzene] (1) were synthesized, by introducing hydroxyl groups in the double bond of the propenyl moiety. Two types of reactions were performed: (i) oxymercuration/demercuration that formed two products, the mono-hydroxyl derivative, 1-hydroxy-1-(4-methoxyphenyl)-propane (2) and in lesser extent the dihydroxyl derivative, 1,2-dihydroxy-1-(4-methoxyphenyl)-propane (3) and (ii) epoxidation with m-chloroperbenzoic acid that also led to the formation of two products, the dihydroxyl derivative (3) and the correspondent m-chloro-benzoic acid mono-ester, 1-hydroxy-1(4-methoxyphenyl)-2-m-chlorobenzoyl-propane (4). The structures of these compounds were confirmed mainly by mass, IR, 1H and 13C NMR spectral data. The activity of anethole and hydroxylated derivatives was evaluated using antioxidant, anti-inflammatory and gastroprotector tests. Compounds (2) and (3) were more active antioxidant agents than (1) and (4). In the anti-inflammatory assay, anethole showed lower activity than hydroxylated derivatives. Anethole and in lesser extent its derivatives 2 and 4 showed significant gastroprotector activity. All tested compounds do not alter significantly the total number of white blood cells.
Yadav, Anoop; Suthar, S; Garg, V K
2015-10-01
This paper reports the changes in microbial parameters and enzymatic activities during vermicomposting of effluent treatment plant sludge (ETPS) of bakery industry spiked with cow dung (CD) by Eisenia fetida. Six vermibins containing different ratios of ETPS and CD were maintained under controlled laboratory conditions for 15 weeks. Total bacterial and total fungal count increased upto 7th week and declined afterward in all the bins. Maximum bacterial and fungal count was 31.6 CFU × 10(6) g(-1) and 31 CFU × 10(4) g(-1) in 7th week. Maximum dehydrogenase activity was 1921 μg TPF g(-1) h(-1) in 9th week in 100 % CD containing vermibin, whereas maximum urease activity was 1208 μg NH4 (-)N g(-1) h(-1) in 3rd week in 100 % CD containing vermibin. The enzyme activity and microbial counts were lesser in ETPS containing vermibins than control (100 % CD). The growth and fecundity of the worms in different vermibins were also investigated. The results showed that initially biomass and fecundity of the worms increased but decreased at the later stages due to non-availability of the palatable feed. This showed that quality and palatability of food directly affect biological parameters of the system.
Inequalities in oral health: Understanding the contributions of education and income.
Farmer, Julie; Phillips, Rebecca C; Singhal, Sonica; Quiñonez, Carlos
2017-09-14
To quantify the extent to which income and education explain gradients in oral health outcomes. Using data from the Canadian Community Health Survey (CCHS 2003), binary logistic regression models were constructed to examine the relationship between income and education on self-reported oral health (SROH) and chewing difficulties (CD) while controlling for age, sex, ethnicity, employment status and dental insurance coverage. The relative index of inequality (RII) was utilized to quantify the extent to which income and education explain gradients in poor SROH and CD. Income and education gradients were present for SROH and CD. From fully adjusted models, income inequalities were greater for CD (RIIinc = 2.85) than for SROH (RIIinc = 2.75), with no substantial difference in education inequalities between the two. Income explained 37.4% and 42.4% of the education gradient in SROH and CD respectively, whereas education explained 45.2% and 6.1% of income gradients in SROH and CD respectively. Education appears to play a larger role than income when explaining inequalities in SROH; however, it is the opposite for CD. In this sample of the Canadian adult population, income explained over one third of the education gradient in SROH and CDs, whereas the contribution of education to income gradients varied by choice of self-reported outcome. Results call for stakeholders to improve affordability of dental care in order to reduce inequalities in the Canadian population.
Avanzino, Laura; Ravaschio, Andrea; Lagravinese, Giovanna; Bonassi, Gaia; Abbruzzese, Giovanni; Pelosin, Elisa
2018-01-01
It is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor. Twenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: (i) the anticipatory adjustment (just before the impact); (ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase. The anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor. Patients with cervical dystonia and tremor display an abnormal predictive movement control. Our findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
Imaging findings of intestinal tuberculosis.
Engin, Gulgun; Balk, Emre
2005-01-01
Intestinal tuberculosis (TB) has 3 main forms: ulcerative, hypertrophic or ulcerohypertrophic, and fibrous stricturing. In the ulcerative form, barium examination reveals thickened folds, spasticity, and shallow ulcers involving the cecum and terminal ileum. Computerized tomography shows preferential thickening of the ileocecal valve and medial wall of the cecum as well as a few small regional nodes. In the hypertrophic or ulcerohypertrophic form, a hyperplastic reaction is seen in the exophytic masses around the ulcerated lumen on computed tomography. An inflammatory mass that extends into adjacent muscle suggests TB. In the sclerotic form, the main reaction is fibrosis with single or multiple short strictures. The cecum classically becomes amputated, conical, shrunken, and retracted. In comparison, Crohn's disease (CD) has a rather uniform and lesser thickening of the bowel wall. Mural stratification, vascular jejunization or the comb sign, and mesenteric fibrofatty proliferation are seen only in CD. The hypertrophic form may also mimic malignant neoplasms, such as lymphoma or carcinoma. Cecal carcinoma rarely extends beyond the ileocecal valve, however. In lymphoma, it can be seen as a greater degree of wall thickness with aneurysmatic dilation of the intestinal lumen. Single or multiple strictures are also seen as a CD complication. Advanced skip lesions adjacent to the stricture are usually diagnostic for CD.
Qandil, Amjad M.; Al-Zoubi, Lorca O.; Al-Bakri, Amal G.; Amawi, Haneen A.; Al-Balas, Qosay A.; Alkatheri, Abdulmalik M.; Albekairy, Abdulkareem M.
2014-01-01
Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 μM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity. PMID:27025747
Cholesterol-loaded-cyclodextrins improve the post-thaw quality of stallion sperm.
Murphy, C; English, A M; Holden, S A; Fair, S
2014-03-01
An unacceptable proportion of stallion sperm do not survive the freeze-thaw process. The hypothesis of this study was that adding cholesterol to a stallion semen extender would stabilise the sperm membrane, resulting in an improved post-thaw semen quality in terms of increased sperm viability, membrane integrity and fluidity, and reduced oxidative stress. Semen was collected from three stallions and diluted in four extenders: TALP; TALP+0.75mg methyl-β-cyclodextrin-cholesterol (MβCD)/mL (MβCD0.75); TALP+1.5mg MβCD-cholesterol/mL (MβCD1.5); and Equipro. Following 15min incubation, samples were centrifuged and diluted to 100×10(6)sperm/mL, frozen in 0.5mL straws and stored in liquid nitrogen. Sperm from each treatment was assessed for progressive linear motility (PLM) and acceptable membrane integrity under hypotonic conditions on a phase contrast microscope at 1000× while viability, membrane fluidity and superoxide generation were assessed by flow cytometry. The MβCD1.5 and MβCD0.75 treatments had a greater proportion of viable sperm than the TALP treatment (P<0.01). There was no effect of treatment on PLM or membrane integrity. The MβCD1.5 treatment had a greater proportion of viable sperm positive for membrane fluidity than the TALP treatment (P<0.05). The MβCD1.5 and MβCD0.75 treatments had a lesser proportion of viable sperm positive for superoxide generation than the TALP treatment (P<0.001). This study has demonstrated that adding cholesterol to stallion sperm prior to cryopreservation increases post-thaw viability, with these viable sperm being of better quality in terms of increased membrane fluidity and reduced superoxide generation. Copyright © 2014 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Krien, Yann; Dudon, Bernard; Roger, Jean; Arnaud, Gael; Zahibo, Narcisse
2017-09-01
In the Lesser Antilles, coastal inundations from hurricane-induced storm surges pose a great threat to lives, properties and ecosystems. Assessing current and future storm surge hazards with sufficient spatial resolution is of primary interest to help coastal planners and decision makers develop mitigation and adaptation measures. Here, we use wave-current numerical models and statistical methods to investigate worst case scenarios and 100-year surge levels for the case study of Martinique under present climate or considering a potential sea level rise. Results confirm that the wave setup plays a major role in the Lesser Antilles, where the narrow island shelf impedes the piling-up of large amounts of wind-driven water on the shoreline during extreme events. The radiation stress gradients thus contribute significantly to the total surge - up to 100 % in some cases. The nonlinear interactions of sea level rise (SLR) with bathymetry and topography are generally found to be relatively small in Martinique but can reach several tens of centimeters in low-lying areas where the inundation extent is strongly enhanced compared to present conditions. These findings further emphasize the importance of waves for developing operational storm surge warning systems in the Lesser Antilles and encourage caution when using static methods to assess the impact of sea level rise on storm surge hazard.
Semenova, Tatiana A.; Morgado, Luis N.; Welker, Jeffrey M.
2016-01-01
We characterized fungal communities in dry and moist tundra and investigated the effect of long-term experimental summer warming on three aspects of functional groups of arctic fungi: richness, community composition and species abundance. Warming had profound effects on community composition, abundance, and, to a lesser extent, on richness of fungal functional groups. In addition, our data show that even within functional groups, the direction and extent of response to warming tend to be species-specific and we recommend that studies on fungal communities and their roles in nutrient cycling take into account species-level responses. PMID:27881760
Dudani, Renu; Murali-Krishna, Kaja; Krishnan, Lakshmi; Sad, Subash
2014-01-01
Memory T cells are critical for the control of intracellular pathogens and require few signals for maintenance; however, erosion of established preexisting memory CD8+ T cells has been shown to occur during infection with heterologous viral infections. We evaluated whether this also occurs during infection with various intracellular bacteria and what mechanisms may be involved. We demonstrate that erosion of established memory is also induced during infection of mice with various intracellular bacteria, such as Listeria monocytogenes, Salmonella typhimurium, and Mycobacterium bovis (bacillus Calmette-Guérin). The extent of erosion of established CD8+ T cell memory was dependent on the virulence of the heterologous pathogen, not persistence. Furthermore, when antibiotics were used to comprehensively eliminate the heterologous pathogen, the numbers of memory CD8+ T cells were not restored, indicating that erosion of preexisting memory CD8+ T cells was irreversible. Irrespective of the initial numbers of memory CD8+ T cells, challenge with the heterologous pathogen resulted in a similar extent of erosion of memory CD8+ T cells, suggesting that cellular competition was not responsible for erosion. After challenge with the heterologous pathogen, effector memory CD8+ T cells were rapidly eliminated. More importantly, erosion of preexisting memory CD8+ T cells was abrogated in the absence of IFN-γ. These studies help reveal the paradoxical role of IFN-γ. Although IFN-γ promotes the control of intracellular bacterial replication during primary infection, this comes at the expense of erosion of preexisting memory CD8+ T cells in the wake of infection with heterologous pathogens. PMID:18641306
Navy Job-Related Male-Female Differences: Annotated Bibliography.
1982-04-01
and 50 female Caucasian South African healing sciences students and 44 male and 43 female American medical, dental, physiotherapy students were...lesser extent, even the primary differences. The subjects used in the cited research, especially in the cognitive areas, were usually college students ...that may make college students atypical of and noncomparable to Navy enlisted personnel of the same general age. This appears more likely for males
Economic dynamics of forests and forest industries in the Southern United States
Thomas J. Brandeis; Andrew J. Hartsell; James W. Bentley; Consuelo Brandeis
2012-01-01
This report reviews how recent (2005-present) economic conditions have accelerated mill closings and job losses, and, to a lesser extent, influenced forest management in the Southern United States. We show that the number of primary roundwood-using mills has decreased across the South since the 1970s. At the same time, mill output has increased as the production of the...
ERIC Educational Resources Information Center
Kesner, Richard M.; Russell, Bruce
2009-01-01
The "FastFit Case Study" and its companion, the "Winter Gear Distributors Case Study" provide undergraduate business students with a suitable and even familiar business context within which to initially consider the role of information management (IM) and to a lesser extent the role of information technology (IT) systems in enabling a business.…
What the Discourse Tells Us: Talk and Indicators of High-Level Comprehension
ERIC Educational Resources Information Center
Soter, Anna O.; Wilkinson, Ian A.; Murphy, P. Karen; Rudge, Lucila; Reninger, Kristin; Edwards, Margaret
2008-01-01
The purpose of this study was to validate and extend the findings of an exhaustive literature search in Year 1 and a meta-analysis in Year 2 of a 3-year project in which nine (9) small-group discussion approaches were identified. Having identified parameters of discussion that were, to a greater or lesser extent, present in these nine discussion…
ERIC Educational Resources Information Center
January, Stacy-Ann A.; Ardoin, Scott P.; Christ, Theodore J.; Eckert, Tanya L.; White, Mary Jane
2016-01-01
Universal screening in elementary schools often includes administering curriculum-based measurement in reading (CBM-R); but in first grade, nonsense word fluency (NWF) and, to a lesser extent, word identification fluency (WIF) are used because of concerns that CBM-R is too difficult for emerging readers. This study used Kane's argument-based…
ERIC Educational Resources Information Center
Uny, I.; France, E. F.; Noblit, G. W.
2017-01-01
Since its inception in the 1980s, the meta-ethnography approach for synthesising qualitative study accounts has been used extensively in health and social care research and to a lesser extent in educational research. The aim of this article is to reflect on the evolution of the method in both fields. It starts by describing the meta-ethnography…
Age and Ethnic Differences in Cold Weather and Contagion Theories of Colds and Flu
ERIC Educational Resources Information Center
Sigelman, Carol K.
2012-01-01
Age and ethnic group differences in cold weather and contagion or germ theories of infectious disease were explored in two studies. A cold weather theory was frequently invoked to explain colds and to a lesser extent flu but became less prominent with age as children gained command of a germ theory of disease. Explanations of how contact with…
Poisson filtering of laser ranging data
NASA Technical Reports Server (NTRS)
Ricklefs, Randall L.; Shelus, Peter J.
1993-01-01
The filtering of data in a high noise, low signal strength environment is a situation encountered routinely in lunar laser ranging (LLR) and, to a lesser extent, in artificial satellite laser ranging (SLR). The use of Poisson statistics as one of the tools for filtering LLR data is described first in a historical context. The more recent application of this statistical technique to noisy SLR data is also described.
ERIC Educational Resources Information Center
BAYES, KENNETH
CURRENT RESEARCH AND THOUGHT ON THE EFFECTS OF ARCHITECTURAL FORM AND COLOR IN THE TREATMENT OF EMOTIONALLY DISTURBED AND RETARDED CHILDREN ARE SURVEYED IN THIS PUBLICATION. TO A LESSER EXTENT, IT COVERS THE RELATIONSHIP OF THERAPY TO BEHAVIOR, NORMAL CHILDREN TO HANDICAPPED CHILDREN, NORMAL ADULTS TO MENTAL PATIENTS, AND CHILDREN TO ADULTS.…
ERIC Educational Resources Information Center
Ehman, Lee H.
The paper reports findings of a three year longitudinal study of high school student social and political attitudes. The hypothesis was that openness of social studies classroom climate would be related to change in social and political attitudes toward school and, to a lesser extent, to change in general social and political attitudes. Attitude…
A Teacher's Guide to the Energy 80 Student Booklet for the 1981-82 School Year.
ERIC Educational Resources Information Center
Lord, John, Ed.
This teaching guide was developed for use with Energy 80 program student booklets. Although the program was designed for junior high/middle school students in science/social studies classes, it is indicated that the materials are suitable for use at higher grades and, to a lesser extent, in upper elementary grades. The first 80 pages of the guide…
Code of Federal Regulations, 2010 CFR
2010-04-01
... business with respect to which the plan is established, or $2,500, whichever is the lesser. This is the... contributions shall be considered to satisfy the conditions of section 162 (relating to trade or business expenses) or 212 (relating to expenses for the production of income), but only to the extent that such...
Eskildsen, Anita; Fentz, Hanne Nørr; Andersen, Lars Peter; Pedersen, Anders Degn; Kristensen, Simon Bang; Andersen, Johan Hviid
2017-07-01
Patients on sick leave due to work-related stress often present with cognitive impairments as well as sleep disturbances. The aim of this longitudinal study was to examine the role of perceived stress and sleep disturbances in the longitudinal development in cognitive impairments in a group of patients with prolonged work-related stress (N = 60) during a period of 12 months following initial professional care-seeking. Objective cognitive impairments (neuropsychological tests) were measured on two occasions - at initial professional care-seeking and at 12-month follow-up. Questionnaires on perceived stress, sleep disturbances, and cognitive complaints were completed seven times during the 12 months which facilitated multilevel analysis with segregation of within-person (change) and between-person (baseline level) components of the time-varying predictors (perceived stress and sleep disturbances). Change in perceived stress was associated with concurrent and subsequent change in self-reported cognitive complaints over the period of 12 months and to a lesser extent the change in performance on neuropsychological tests of processing speed from baseline to 12-month follow-up. Change in sleep disturbances was also associated with concurrent and subsequent change in self-reported cognitive complaints over the 12 months but not with change on neuropsychological test performance. Although the mechanism behind the improvement in cognitive impairments in patients with work-related stress should be further explored in future studies, the results could suggest that improvement in cognitive impairments is partly mediated by decreasing levels of perceived stress and, to a lesser extent, decreasing levels of sleep disturbances. Lay summary This study examines the role of perceived stress and sleep disturbances in respect to the development of cognitive impairments (e.g. memory and concentration) in a group of patients with work-related stress. We found that change in cognitive impairments seems to be partly explained by change in perceived stress and, to a lesser extent, sleep disturbances over time. This could suggest that cognitive impairments can be reduced by stress management interventions which aim to reduce perceived stress and sleep disturbances but future studies are needed to confirm this interpretation.
Dunne, Margaret R.; Ryan, Ciara; Nolan, Bláthnaid; Tosetto, Miriam; Geraghty, Robert; Winter, Des C.; O’Connell, P. Ronan; Hyland, John M.; Doherty, Glen A.; Sheahan, Kieran; Ryan, Elizabeth J.; Fletcher, Jean M.
2016-01-01
T cell infiltration into colorectal tumors has been shown to correlate with improved patient outcomes. However, more detailed information on the makeup and relationships between the infiltrating T cell subsets is lacking. We therefore correlated the extent of immune infiltration into colorectal tumors with the frequencies of various T cell subsets. We prospectively recruited 22 patients at the time of surgical resection for colorectal cancer. The Klintrup–Mäkinen (KM) score was used to estimate the extent of immune infiltration into colorectal tumors. The frequencies of CD4 and CD8 T cells that produced cytokines or expressed the inhibitory molecule programed cell death 1 (PD-1) were determined by flow cytometry in colorectal tumor and matched uninvolved colonic tissue. In addition, the frequency of CD4 regulatory T cell (Treg) subsets was determined. An increased frequency of CD4 T cells producing IL-17 (Th17 cells) was observed in colorectal tumor tissue compared with adjacent uninvolved tissue. These Th17 cells mostly coproduced TNF-α, but not IFN-γ. IL-17 expression correlated positively with TNF-α and IL-10. Increased expression of the immune checkpoint molecule PD-1 was found in colorectal tumors compared with adjacent uninvolved tissue. There was a negative correlation between expression of PD-1 and IFN-γ, but not IL-17, for both CD4+ and CD8+ T cells. CD4+CD25+CD127lo and CD4+CD25+CD127loFoxP3+CD39+ Treg cells were enriched in colorectal tumors. A positive correlation between KM score and percentage CD4+CD25+CD127lo Treg cells was observed in tumors, suggesting that increased immune infiltration is associated with an increased proportion of Treg cells. In addition, there was a negative correlation between the frequency of CD4+CD25+CD127lo Treg cells and the expression of IFN-γ and IL-2, but not IL-17, in tumors. Taken together, these data suggest that both PD-1 expressing T cells and Treg cells within the tumor may have a suppressive effect on T cells secreting IFN-γ, IL-2, or TNF-α, but not Th17 cells. PMID:27014625
Sonuga-Barke, Edmund J S; Coghill, David; DeBacker, Marc; Swanson, James
2009-12-01
Methylphenidate (MPH) is an efficacious and normally well-tolerated treatment for attention-deficit/hyperactivity disorder (ADHD). Although treatment effects are usually assessed using parent-rating scales, these can be supplemented by more objective methods. Here we examine the associations between ratings and one such method, assessments made across the day in the laboratory classroom. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Treatment effects were observed on all measures. Laboratory measures were correlated with each other, most strongly between Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP) inattention and Permanent Product Measure of Performance (PERMP). Parental ratings were correlated with classroom measures during the main morning period (1.5-4.5 hours after dosing) and to a lesser extent in the afternoon (6.0-7.5 hours after dosing), but not, by and large, immediately after dosing or in the evening. The morning correlations seemed stronger for female than for male participants. The results suggest that parental ratings and direct observations tap different aspects of MPH response and that both may be required for comprehensive assessment.
Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function
Theron, A. J.; Steel, H. C.; Tintinger, G. R.; Gravett, C. M.; Anderson, R.; Feldman, C.
2014-01-01
Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies. PMID:24971371
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harvey, R.W.; Nevins, W.M.; Smith, G.R.
Electron cyclotron (EC) power has technological and physics advantages for heating and current drive in a tokamak reactor, and advances in source development make it credible for applications in ITER. Strong single pass absorption makes heating to ignition particularly simple. The optimized EC current drive (ECCD) efficiency ({l_angle}n{r_angle}IR/P) shows a linear temperature scaling at temperatures up to {approximately} 15 keV. For temperatures above 30 keV, the efficiency saturates at approximately 0.3{center_dot}10{sup 20} A/(m{sup 2}W) for a frequency of 220 GHz in an ITER target plasma with toroidal field of 6 T, due primarily to harmonic overlap [G.R. Smith et al.,more » Phys. Fluids 30 3633 (1987)] and to a lesser extent due to limitations arising from relativistic effects [N.J. Fisch, Phys. Rev. A 24 3245 (1981)]. The same efficiency can also be obtained at 170 GHz for the same plasma equilibrium except that the magnetic field is reduced to (170/220) {times} 6 T = 4.6 T. The ECCD efficiencies are obtained with the comprehensive 3D, bounce-averaged Fokker-Planck CQL3D codes [R.W. Harvey and M.G. McCoy, Proc. IAEA TCM/Advances in Simulation and Modeling in Thermonuclear Plasmas 1992, Montreal], and BANDIT3D [M.R. O`Brien, M. Cox, C.D. Warrick, and F. S. Zaitsev, ibid.].« less
Berta, Ágnes I.; Boesze-Battaglia, Kathleen; Genini, Sem; Goldstein, Orly; O'Brien, Paul J.; Szél, Ágoston; Acland, Gregory M.; Beltran, William A.; Aguirre, Gustavo D.
2011-01-01
A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell proliferation is associated with increased cyclin A1 and LATS1 mRNA expression, but CRX protein expression is unchanged. Coincident with photoreceptor proliferation is a change in the photoreceptor population. Prior to cell death the photoreceptor mosaic is composed of L/M- and S-cones, and rods. After proliferation, both cone types remain, but the majority of rods are now hybrid photoreceptors that express rod opsin and, to a lesser extent, cone S-opsin, and lack NR2E3 expression. The hybrid photoreceptors renew their outer segments diffusely, a characteristic of cones. The results indicate the capacity for terminally differentiated, albeit mutant, photoreceptors to divide with mutations in this novel retinal degeneration gene. PMID:21980341
Intriguing olfactory proteins from the yellow fever mosquito, Aedes aegypti
NASA Astrophysics Data System (ADS)
Ishida, Yuko; Chen, Angela M.; Tsuruda, Jennifer M.; Cornel, Anthon J.; Debboun, Mustapha; Leal, Walter S.
2004-09-01
Four antennae-specific proteins (AaegOBP1, AaegOBP2, AaegOBP3, and AaegASP1) were isolated from the yellow fever mosquito, Aedes aegypti and their full-length cDNAs were cloned. RT-PCR indicated that they are expressed in female and, to a lesser extent, in male antennae, but not in control tissues (legs). AaegOBP1 and AaegOBP3 showed significant similarity to previously identified mosquito odorant-binding proteins (OBPs) in cysteine spacing pattern and sequence. Two of the isolated proteins have a total of eight cysteine residues. The similarity of the spacing pattern of the cysteine residues and amino acid sequence to those of previously identified olfactory proteins suggests that one of the cysteine-rich proteins (AaegOBP2) is an OBP. The other (AaegASP1) did not belong to any group of known OBPs. Structural analyses indicate that six of the cysteine residues in AaegOBP2 are linked in a similar pattern to the previously known cysteine pairing in OBPs, i.e., Cys-24 Cys-55, Cys-51 Cys-104, Cys-95 Cys-113. The additional disulfide bridge, Cys-38 Cys-125, knits the extended C-terminal segment of the protein to a predicted α2-helix. As indicated by circular dichroism (CD) spectra, the extra rigidity seems to prevent the predicted formation of a C-terminal α-helix at low pH.
IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis.
Elizei, Sanam Salimi; Pakyari, Mohammadreza; Ghoreishi, Mehraneh; Kilani, Ruhangiz; Mahmoudi, Sanaz; Ghahary, Aziz
2018-01-01
Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1.9% ± 0.3% vs. 6.9% ± 0.6%, n = 3, P value < 0.01), IL-17+ γδ+ T cells (2.8% ± 0.3% vs. 11.6% ± 1.2%, n = 3, P value < 0.01), IL-23+ activated dendritic cells (7.6% ± 0.9% vs. 14.0% ± 0.5%, n = 3, P < 0.01), macrophages (4.3% ± 0.1% vs. 11.3% ± 1.0%, n = 3, P value < 0.01), and granulocytes (2.5% ± 0.4% vs. 4.5% ± 0.3%, n = 3, P value < 0.01) as compared to untreated psoriatic mice. This finding suggests that IDO-expressing fibroblasts, and to a lesser extent, non-IDO primary fibroblasts suppress the psoriatic-like symptoms by inhibiting the infiltration of key immune cells involved in the development of psoriasis.
Webb, Elisabeth B.; Fowler, Drew N.; Woodall, Brendan A.; Vrtiska, Mark P.
2018-01-01
Assessing nutrient stores in avian species is important for understanding the extent to which body condition influences success or failure in life‐history events. We evaluated predictive models using morphometric characteristics to estimate total body lipids (TBL) and total body protein (TBP), based on traditional proximate analyses, in spring migrating lesser snow geese (Anser caerulescens caerulescens) and Ross's geese (A. rossii). We also compared performance of our lipid model with a previously derived predictive equation for TBL developed for nesting lesser snow geese. We used external and internal measurements on 612 lesser snow and 125 Ross's geese collected during spring migration in 2015 and 2016 within the Central and Mississippi flyways to derive and evaluate predictive models. Using a validation data set, our best performing lipid model for snow geese better predicted TBL (root mean square error [RMSE] of 23.56) compared with a model derived from nesting individuals (RMSE = 48.60), suggesting the importance of season‐specific models for accurate lipid estimation. Models that included body mass and abdominal fat deposit best predicted TBL determined by proximate analysis in both species (lesser snow goose, R2 = 0.87, RMSE = 23.56: Ross's geese, R2 = 0.89, RMSE = 13.75). Models incorporating a combination of external structural measurements in addition to internal muscle and body mass best predicted protein values (R2 = 0.85, RMSE = 19.39 and R2 = 0.85, RMSE = 7.65, lesser snow and Ross's geese, respectively), but protein models including only body mass and body size were also competitive and provided extended utility to our equations for field applications. Therefore, our models indicated the importance of specimen dissection and measurement of the abdominal fat pad to provide the most accurate lipid estimates and provide alternative dissection‐free methods for estimating protein.
NASA Astrophysics Data System (ADS)
Laurencin, M.; Marcaillou, B.; Graindorge, D.; Klingelhoefer, F.; Lallemand, S.; Laigle, M.; Lebrun, J.-F.
2017-05-01
The influence of the highly oblique plate convergence at the northern Lesser Antilles onto the margin strain partitioning and deformation pattern, although frequently invoked, has never been clearly imaged. The Anegada Passage is a set of basins and deep valleys, regularly related to the southern boundary of the Puerto Rico-Virgin Islands (PRVI) microplate. Despite the publications of various tectonic models mostly based on bathymetric data, the tectonic origin and deformation of this Passage remains unconstrained in the absence of deep structure imaging. During cruises Antithesis 1 and 3 (2013-2016), we recorded the first deep multichannel seismic images and new multibeam data in the northern Lesser Antilles margin segment in order to shed a new light on the structure and tectonic pattern of the Anegada Passage. We image the northeastern extent of the Anegada Passage, from the Sombrero Basin to the Lesser Antilles margin front. Our results reveal that this northeastern segment is an EW trending left-stepping en échelon strike-slip system that consists of the Sombrero and Malliwana pull-apart basins, the Malliwana and Anguilla left-lateral faults, and the NE-SW compressional restraining bend at the Malliwana Hill. Reviewing the structure of the Anegada Passage, from the south of Puerto Rico to the Lesser Antilles margin front, reveals a polyphased tectonic history. The Anegada Passage is formed by a NW-SE extension, possibly related to the rotation or escape of PRVI block due to collision of the Bahamas Bank. Currently, it is deformed by an active WNW-ESE strike-slip deformation associated to the shear component of the strain partitioning resulting from the subduction obliquity.
Lavretsky, Philip; Peters, Jeffrey L; Winker, Kevin; Bahn, Volker; Kulikova, Irina; Zhuravlev, Yuri N; Wilson, Robert E; Barger, Chris; Gurney, Kirsty; McCracken, Kevin G
2016-02-01
Estimating the frequency of hybridization is important to understand its evolutionary consequences and its effects on conservation efforts. In this study, we examined the extent of hybridization in two sister species of ducks that hybridize. We used mitochondrial control region sequences and 3589 double-digest restriction-associated DNA sequences (ddRADseq) to identify admixture between wild lesser scaup (Aythya affinis) and greater scaup (A. marila). Among 111 individuals, we found one introgressed mitochondrial DNA haplotype in lesser scaup and four in greater scaup. Likewise, based on the site-frequency spectrum from autosomal DNA, gene flow was asymmetrical, with higher rates from lesser into greater scaup. However, using ddRADseq nuclear DNA, all individuals were assigned to their respective species with >0.95 posterior assignment probability. To examine the power for detecting admixture, we simulated a breeding experiment in which empirical data were used to create F1 hybrids and nine generations (F2-F10) of backcrossing. F1 hybrids and F2, F3 and most F4 backcrosses were clearly distinguishable from pure individuals, but evidence of admixed histories was effectively lost after the fourth generation. Thus, we conclude that low interspecific assignment probabilities (0.011-0.043) for two lesser and nineteen greater scaup were consistent with admixed histories beyond the F3 generation. These results indicate that the propensity of these species to hybridize in the wild is low and largely asymmetric. When applied to species-specific cases, our approach offers powerful utility for examining concerns of hybridization in conservation efforts, especially for determining the generational time until admixed histories are effectively lost through backcrossing. © 2015 John Wiley & Sons Ltd.
An Item Response Theory Analysis of DSM-IV Conduct Disorder
ERIC Educational Resources Information Center
Gelhorn, Heather; Hartman, Christie; Sakai, Joseph; Mikulich-Gilbertson, Susan; Stallings, Michael; Young, Susan; Rhee, Soo; Corley, Robin; Hewitt, John; Hopfer, Christian; Crowley, Thomas
2009-01-01
Interviews with over 3,000 adolescents were made to evaluate the extent to which DSM-IV criteria characterizes the range of severity of adolescent antisocial behavior within and across sex. The DSM-IV conduct disorder (CD) criteria are a useful indicator of severe adolescent antisocial behavior but some CD criteria display sex bias.
Our Crowded Shores: Balancing Growth and Resource Protection. [CD-ROM].
ERIC Educational Resources Information Center
National Oceanic and Atmospheric Administration (DOC), Washington, DC. Environmental Data Service.
This interactive educational CD-ROM is designed for the general public and examines the extent of coastal population growth and development and their impact on coastal resources. High schools will find it a useful complement to environmental sciences curricula while science and visitors centers, museums, and aquariums will discover it to be a…
Defense Acquisition Reform, 19602009: An Elusive Goal
2011-10-31
the seven largest economies of the world (United States, China, Japan, Germany , France, United Kingdom, and Italy).11 Major weapon systems...and to a lesser extent, Germany ) compared with that of the United States was an im- portant reason for Japan’s higher rate of productivity growth...professions and areas of expertise. DoD vetted prospects from non-defense businesses such as insurance and cruise lines, from organized labor, and
ERIC Educational Resources Information Center
Moffitt, Robert; Winder, Katie
The dramatic decline in Temporary Assistance for Needy Families (TANF) caseloads in the 1990s has focused attention on the process of exit from, and, to a lesser extent, entry into, the welfare system. This paper charts the process of turnover in the TANF program in three major U.S. cities over an 18-month, post-PWORA period and documents its…
NASA Technical Reports Server (NTRS)
1985-01-01
These unique weathered volcanic intrusions near Wadi Habawnah, Saudi Arabia (18.0N, 44.0E) are located near Najran, north of the Yemen border. This harsh and rugged desert landscape has been heavily wind eroded and, to a lesser extent, water eroded, as evidenced by the dendritic patterns in this region where rainfall is a seldom occurance. Only a dwindling number of nomadic tribes inhabit this harsh region of few resources.
Nutrient status and plant growth effects of forest soils in the Basin of Mexico
Mark E. Fenn; V.M. Perea-Estrada; L.I. de Bauer; M. Pérez-Suárez; D.R. Parker; V.M. Cetina-Alcalá
2006-01-01
The nutrient status of forest soils in the Mexico City Air Basin was evaluated by observing plant growth responses to fertilization with N, P or both nutrients combined. P deficiency was the most frequent condition for soil from two high pollution sites and N deficiency was greatest at a low N deposition site. Concentrations of Pb and Ni, and to a lesser extent Zn and...
ERIC Educational Resources Information Center
Policy Studies Associates, Inc., Washington, DC.
This report describes the research design of a study that identified and evaluated a collection of reforms designed to enhance learning by altering the amount of and/or the quality of time devoted to learning. The study focused on the quantity and quality of time that teachers and students spent in school and, to a lesser extent, students'…
2016-12-22
in both the energy received and the travel time , both exhibiting strong 3D propagation. A paper was published on using noise correlations to estimate...3-5 Hz. 3.2. Passive Acoustic Thermometry From theoretical considerations it follows that the acoustic travel time between two sensors can be...obtained from the ambient noise field. In underwater acoustics, this travel time strongly depends on the depth and temperature and to a lesser extent
From Insurgency to Stability. Volume 2: Insights from Selected Case Studies
2011-01-01
Venezuela; and, to a lesser extent Ecuador , Panama, and Brazil. Cuba has facilitated discussions between the Colombian government and the ELN, and some...regroup and rebuild inside Venezuela and possibly Ecuador . Despite occasional pronouncements from President Chavez that his government is not...interest to the U.S. Department of Defense, other agencies of the U.S. government , as well as government and nongovernmental orga- nizations in other
ERIC Educational Resources Information Center
Elderton, Anna; Clarke, Sally; Jones, Chris; Stacey, James
2014-01-01
Historically, and to a somewhat lesser extent presently, people with learning disabilities have had little or no voice in the stories other people (particularly professionals) tell about them and their lives. Four psychology workshops, based on a narrative therapy approach, were run for a group of people with learning disabilities who identify as…
Nagatomo, Kazuya; Yabuuchi, Hidetake; Yamasaki, Yuzo; Narita, Hiroshi; Kumazawa, Seiji; Kojima, Tsukasa; Sakai, Noriyuki; Masaki, Masahumi; Kimura, Hiroshi
2016-10-01
To elucidate the utility of PROPELLER for motion artefact reduction on shoulder MRI and to examine the influence of streak artefacts on diagnosis of clinical images. 15 healthy volunteers and 48 patients underwent shoulder MRI with/without PROPELLER (coronal oblique proton density-fast spin echo [PD-FSE], sagittal oblique T2-FSE). In a volunteer study, all sequences were performed in both static and exercise-loaded conditions. Two radiologists graded artefacts and delineation of various anatomical structures in the volunteer study and motion and streak artefacts in the clinical study. Mean scores were compared between sequences with/without PROPELLER. In the clinical study, mean scores of motion artefacts were compared with mean scores of streak artefacts. Wilcoxon signed-rank test was used for all comparisons. In both studies, PROPELLER significantly reduced motion artefacts (P<0.05). In the volunteer study, it significantly improved delineations in sagittal oblique images in the exercise-loaded condition (P<0.05). In the clinical study, streak artefacts appeared dominantly on images with PROPELLER (P<0.05), but influenced diagnosis to a lesser extent than motion artefacts. PROPELLER can reduce motion artefacts in shoulder MRI. While it does cause streak artefacts, it affects diagnosis to a lesser extent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Minero, Claudio; Maurino, Valter; Bono, Francesca; Pelizzetti, Ezio; Marinoni, Angela; Mailhot, Gilles; Carlotti, Maria Eugenia; Vione, Davide
2007-08-01
The effect of selected organic and inorganic compounds, present in snow and cloudwater was studied. Photolysis of solutions of nitrate to nitrite was carried out in the laboratory using a UVB light source. The photolysis and other reactions were then modelled. It is shown that formate, formaldehyde, methanesulphonate, and chloride to a lesser extent, can increase the initial formation rate of nitrite. The effect, particularly significant for formate and formaldehyde, is unlikely to be caused by scavenging of hydroxyl radicals. The experimental data obtained in this work suggest that possible causes are the reduction of nitrogen dioxide and nitrate by radical species formed on photooxidation of the organic compounds. Hydroxyl scavenging by organic and inorganic compounds would not affect the initial formation rate of nitrite, but would protect it from oxidation, therefore, increasing the concentration values reached at long irradiation times. The described processes can be relevant to cloudwater and the quasi-liquid layer on the surface of ice and snow, considering that in the polar regions irradiated snow layers are important sources of nitrous acid to the atmosphere. Formate and (at a lesser extent) formaldehyde are the compounds that play the major role in the described processes of nitrite/nitrous acid photoformation by initial rate enhancement and hydroxyl scavenging.
Greaves, Paul; Clear, Andrew; Coutinho, Rita; Wilson, Andrew; Matthews, Janet; Owen, Andrew; Shanyinde, Milensu; Lister, T. Andrew; Calaminici, Maria; Gribben, John G.
2013-01-01
Purpose The immune microenvironment is key to the pathophysiology of classical Hodgkin lymphoma (CHL). Twenty percent of patients experience failure of their initial treatment, and others receive excessively toxic treatment. Prognostic scores and biomarkers have yet to influence outcomes significantly. Previous biomarker studies have been limited by the extent of tissue analyzed, statistical inconsistencies, and failure to validate findings. We aimed to overcome these limitations by validating recently identified microenvironment biomarkers (CD68, FOXP3, and CD20) in a new patient cohort with a greater extent of tissue and by using rigorous statistical methodology. Patients and Methods Diagnostic tissue from 122 patients with CHL was microarrayed and stained, and positive cells were counted across 10 to 20 high-powered fields per patient by using an automated system. Two statistical analyses were performed: a categorical analysis with test/validation set-defined cut points and Kaplan-Meier estimated outcome measures of 5-year overall survival (OS), disease-specific survival (DSS), and freedom from first-line treatment failure (FFTF) and an independent multivariate analysis of absolute uncategorized counts. Results Increased CD20 expression confers superior OS. Increased FOXP3 expression confers superior OS, and increased CD68 confers inferior FFTF and OS. FOXP3 varies independently of CD68 expression and retains significance when analyzed as a continuous variable in multivariate analysis. A simple score combining FOXP3 and CD68 discriminates three groups: FFTF 93%, 62%, and 47% (P < .001), DSS 93%, 82%, and 63% (P = .03), and OS 93%, 82%, and 59% (P = .002). Conclusion We have independently validated CD68, FOXP3, and CD20 as prognostic biomarkers in CHL, and we demonstrate, to the best of our knowledge for the first time, that combining FOXP3 and CD68 may further improve prognostic stratification. PMID:23045593
Bönsch, Claudia; Zuercher, Christoph; Lieby, Patricia; Kempf, Christoph; Ros, Carlos
2010-01-01
Globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin have been identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but their role and mechanism of interaction with the virus are largely unknown. In UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a lesser extent, with CD49e. However, only anti-Gb4Cer antibodies could disturb virus attachment. Only a small proportion of cell-bound viruses were internalized, while the majority became detached from the receptor. When added to uninfected cells, the receptor-detached virus showed superior cell binding capacity and infectivity. Attachment of B19V to cells triggered conformational changes in the capsid leading to the accessibility of the N terminus of VP1 (VP1u) to antibodies, which was maintained in the receptor-detached virus. VP1u became similarly accessible to antibodies following incubation of B19V particles with increasing concentrations of purified Gb4Cer. The receptor-mediated exposure of VP1u is critical for virus internalization, since capsids lacking VP1 could bind to cells but were not internalized. Moreover, an antibody against the N terminus of VP1u disturbed virus internalization, but only when present during and not after virus attachment, indicating the involvement of this region in binding events required for internalization. These results suggest that Gb4Cer is not only the primary receptor for B19V attachment but also the mediator of capsid rearrangements required for subsequent interactions leading to virus internalization. The capacity of the virus to detach and reattach again would enhance the probability of productive infections. PMID:20826697
Diaz-Amigo, Carmen; Popping, Bert
2012-01-01
Gluten is a commonly used cereal derivative found in bakery products, among other items. In some susceptible individuals, however, it triggers immune responses of different kinds; there is, to a lesser extent, the wheat allergy that is immunoglobulin E (IgE)-mediated and leads to histamine release and typical allergic symptoms. In this case, other water-soluble proteins, like albumins, are also involved. On the other hand, there is, more frequently, celiac disease (CD), where the gluten causes immune reactions in the intestines of certain individuals, leading to degeneration of villi, which typically leads to malabsorption of nutrients and, consequently, malnutrition. The only currently effective health strategy for affected consumers is avoidance of gluten-containing products, based on clear labeling rules. However, despite unanimously accepted Codex definitions by all member jurisdictions, the national implementation of equivalent laws shows significant differences. In the context of CD and in support of the gluten-free statement, regulatory enforcement, as well as manufacturers' quality controls are mostly based on analytical results. However, numerous methods are available, some of which have been validated better than others, and many provide different results on identical samples. Reasons include detection of different gluten components and variability in extraction efficiency due to different buffer compositions, especially from processed foods. Last but not least, the lack of reference materials is hindering the process of generating comparable data across different ELISA kits, as well as other methods. How can such data still be used to support a gluten-free claim? New methodologies, in particular mass spectrometric analysis of gluten derived peptides, are being introduced in numerous laboratories. This methodology is not only capable of detecting gluten derived peptides but can also differentiate between and quantitate wheat, barley, rye, and oat. This paper presents analytical limitations, as well as promising new approaches in support of industry and enforcement activities to ensure compliance with the gluten-free claim under the current regulatory framework.
Steenholdt, Casper; Brynskov, Jørn; Thomsen, Ole Ø; Munck, Lars K; Christensen, Lisbet A; Pedersen, Gitte; Kjeldsen, Jens; Ainsworth, Mark A
2015-11-01
This study assessed the effects of infliximab (IFX) treatment failure on patient-reported outcomes and explored the influence of using personalized treatment in this situation. Sixty-nine Crohn's disease patients with IFX treatment failure were randomized to an intensified IFX regimen (n = 36) or personalized treatment defined by IFX and anti-IFX antibodies (n = 33). Health-related quality of life evaluated with the Short Inflammatory Bowel Disease Questionnaire (IBDQ) and productivity evaluated with the Work Productivity and Activity Impairment Questionnaire (WPAI:CD) were assessed at treatment failure and after 4, 8, 12 and 20 weeks. Median IBDQ score at manifestation of IFX treatment failure was 40 and improved markedly in responders by 11 at weeks 4 and 8 (p < 0.001) and by 13 at weeks 12 and 20 (p < 0.001). Non-responders improved modestly at weeks 12 and 20 (increase of median 4, p < 0.05). Overall activity impairment was high at IFX failure (median 70%) and decreased substantially in responders (40-50%, p < 0.001) and to a lesser extent in non-responders (15-40%, p < 0.05). In employed patients (55%), absenteeism was negligible during the entire study period. However, median presenteeism was 40% at manifestation of IFX failure and decreased only among responders across time (decrease 10-30%, p < 0.05). Although anti-tumour necrosis factor (TNF) therapy was discontinued in most patients handled by personalized treatment, IBDQ and WPAI:CD scores were similar in these patients compared with patients routinely dose-intensified on IFX. Regaining low disease activity after IFX failure is necessary for minimizing patient impairment and indirect disease-related costs. A personalized treatment strategy does not have a negative influence on patient-reported outcomes. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Kehrmann, Jan; Tatura, Roman; Zeschnigk, Michael; Probst-Kepper, Michael; Geffers, Robert; Steinmann, Joerg; Buer, Jan
2014-07-01
The epigenetic regulation of transcription factor genes is critical for T-cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg-specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and is required for stable expression of FOXP3 and suppressive function. We analysed the impact of hypomethylating agents 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate on human CD4(+) CD25(-) T cells for generating demethylation within FOXP3-TSDR and inducing functional Treg cells. Gene expression, including lineage-specifying transcription factors of the major T-cell lineages and their leading cytokines, functional properties and global transcriptome changes were analysed. The FOXP3-TSDR methylation pattern was determined by using deep amplicon bisulphite sequencing. 5-aza-2'-deoxycytidine induced FOXP3-TSDR hypomethylation and expression of the Treg-cell-specific genes FOXP3 and LRRC32. Proliferation of 5-aza-2'-deoxycytidine-treated cells was reduced, but the cells did not show suppressive function. Hypomethylation was not restricted to FOXP3-TSDR and expression of master transcription factors and leading cytokines of T helper type 1 and type 17 cells were induced. Epigallocatechin-3-gallate induced global DNA hypomethylation to a lesser extent than 5-aza-2'-deoxycitidine, but no relevant hypomethylation within FOXP3-TSDR or expression of Treg-cell-specific genes. Neither of the DNA methyltransferase inhibitors induced fully functional human Treg cells. 5-aza-2'-deoxycitidine-treated cells resembled Treg cells, but they did not suppress proliferation of responder cells, which is an essential capability to be used for Treg cell transfer therapy. Using a recently developed targeted demethylation technology might be a more promising approach for the generation of functional Treg cells. © 2014 John Wiley & Sons Ltd.
Effect of nutrition support on immunity in paediatric patients with beta-thalassaemia major.
Tienboon, Prasong
2003-01-01
Nutritional deficiencies have been variably observed in thalassaemia and the aetiology of many of the immune abnormalities in thalassaemic children are poorly defined. Therefore, we tested the hypothesis that certain immune abnormalities have a nutritional basis. Nutritional status, selective quantitative and functional indices of immunity were studied in twelve children (7 females, 5 males; mean age 28 months, SD 5 and range 19.8-35.5), with thalassaemia major before and after a one month period of intensive nutrition support (the study diet consisted of 'Enfapro' liquid formula (Mead Johnson) with added dextrose and corn oil to achieve a caloric density of 1.1 kcal/cc in addition to vitamins and minerals). Each child was provided approximately 150 kcal/day and 4 g of protein/day. Lymphocyte proliferation to Concanavalin A (Con A) (P = 0.008) and Purified Protein Derivative (PPD) (P = 0.002) was depressed upon entry into the study, however the response to Con A attained normal values by the end of the intervention. Compared to baselines, the proliferative response to Con A (P = 0.005) and Phytohemagglutinin A (PHA) (P = 0.031) both improved after the nutrition support. Although there was no general correlation of zinc status with lymphocyte proliferation, normal baseline zinc status was associated with improvement of proliferation. The %CD4 increased (P = 0.036), primarily because of a decrease in total lymphocytes and to lesser extent a decrease in CD8 lymphocytes. Serum immunoglobulin concentrations were found to be elevated on admission but were not significantly affected by the nutrition intervention. C3 concentrations were uniformly depressed on admission but increased by the end of the study protocol (P = 0.037). C4 and CH50 activity were not significantly influenced by the intervention. In conclusion, children with beta thalassaemia have abnormalities of lymphocyte function as well as key complement components that are responsive to nutrition support. In addition, zinc status appears to have an important role in lymphocyte function in these children.
Palmer, Clovis; Hampartzoumian, Taline; Lloyd, Andrew; Zekry, Amany
2008-08-01
Adipose tissue releases pro-inflammatory and anti-inflammatory mediators, including adiponectin, which elicit a broad range of metabolic and immunological effects. The study aim was to determine in subjects infected with chronic hepatitis C virus (HCV) the effects of total adiponectin and its high-molecular-weight (HMW) and low-molecular-weight isoforms on HCV-specific immune responses. Serum levels of total adiponectin and its isoforms were determined by immunoassay. The ex vivo effect of adiponectin on the HCV-specific T-cell response was examined by interferon gamma (IFN-gamma) enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay cytokine assays. The role of the mitogen-activated protein kinase (MAPK) signaling pathway in mediating the adiponectin effect on T cells was also evaluated. We found that serum levels of total and HMW adiponectin were significantly decreased in subjects with chronic HCV and increased body mass index (BMI) compared with HCV-infected lean subjects. The presence of an anti-HCV specific immune response was strongly associated with lower BMI (P = 0.004) and higher serum total (P = 0.01) and HMW (P = 0.02) adiponectin. In ex vivo assays, total adiponectin and the HMW adiponectin isoform enhanced HCV-specific IFN-gamma production (P = 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-gamma response to adiponectin was entirely dependent on the simultaneous presence of both CD4 and CD8 T cells, and to a lesser extent, natural killer cells. Selective inhibition of p38MAPK activity by SB203580 abrogated the IFN-gamma response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response. In chronic HCV, a reciprocal association exists between BMI, adiponectin, and the anti-HCV immune responses, emphasizing the important role played by adiposity in regulating the immune response in HCV infection.
Skowron Volponi, Marta A; McLean, Donald James; Volponi, Paolo; Dudley, Robert
2018-05-01
Clearwing moths are known for their physical resemblance to hymenopterans, but the extent of their behavioural mimicry is unknown. We describe zigzag flights of sesiid bee mimics that are nearly indistinguishable from those of sympatric bees, whereas sesiid wasp mimics display faster, straighter flights more akin to those of wasps. In particular, the flight of the sesiids Heterosphecia pahangensis , Aschistophleps argentifasciata and Pyrophleps cruentata resembles both Tetragonilla collina and T. atripes stingless bees and, to a lesser extent, dwarf honeybees Apis andreniformis , whereas the sesiid Pyrophleps sp. resembles Tachysphex sp. wasps. These findings represent the first experimental evidence for behavioural mimicry in clearwing moths. © 2018 The Author(s).
CD90 (Thy-1)-positive selection enhances osteogenic capacity of human adipose-derived stromal cells.
Chung, Michael T; Liu, Chunjun; Hyun, Jeong S; Lo, David D; Montoro, Daniel T; Hasegawa, Masakazu; Li, Shuli; Sorkin, Michael; Rennert, Robert; Keeney, Michael; Yang, Fan; Quarto, Natalina; Longaker, Michael T; Wan, Derrick C
2013-04-01
Stem cell-based bone tissue engineering with adipose-derived stromal cells (ASCs) has shown great promise for revolutionizing treatment of large bone deficits. However, there is still a lack of consensus on cell surface markers identifying osteoprogenitors. Fluorescence-activated cell sorting has identified a subpopulation of CD105(low) cells with enhanced osteogenic differentiation. The purpose of the present study was to compare the ability of CD90 (Thy-1) to identify osteoprogenitors relative to CD(105). Unsorted cells, CD90(+), CD90(-), CD105(high), and CD105(low) cells were treated with an osteogenic differentiation medium. For evaluation of in vitro osteogenesis, alkaline phosphatase (ALP) staining and alizarin red staining were performed at 7 days and 14 days, respectively. RNA was harvested after 7 and 14 days of differentiation, and osteogenic gene expression was examined by quantitative real-time polymerase chain reaction. For evaluation of in vivo osteogenesis, critical-sized (4-mm) calvarial defects in nude mice were treated with the hydroxyapatite-poly(lactic-co-glycolic acid) scaffold seeded with the above-mentioned subpopulations. Healing was followed using micro-CT scans for 8 weeks. Calvaria were harvested at 8 weeks postoperatively, and sections were stained with Movat's Pentachrome. Transcriptional analysis revealed that the CD90(+) subpopulation was enriched for a more osteogenic subtype relative to the CD105(low) subpopulation. Staining at day 7 for ALP was greatest in the CD90(+) cells, followed by the CD105(low) cells. Staining at day 14 for alizarin red demonstrated the greatest amount of mineralized extracellular matrix in the CD90(+) cells, again followed by the CD105(low) cells. Quantification of in vivo healing at 2, 4, 6, and 8weeks postoperatively demonstrated increased bone formation in defects treated with CD90(+) ASCs relative to all other groups. On Movat's Pentachrome-stained sections, defects treated with CD90(+) cells showed the most robust bony regeneration. Defects treated with CD90(-) cells, CD105(high) cells, and CD105(low) cells demonstrated some bone formation, but to a lesser degree when compared with the CD90(+) group. While CD105(low) cells have previously been shown to possess an enhanced osteogenic potential, we found that CD90(+) cells are more capable of forming bone both in vitro and in vivo. These data therefore suggest that CD90 may be a more effective marker than CD105 to isolate a highly osteogenic subpopulation for bone tissue engineering.
CD90 (Thy-1)-Positive Selection Enhances Osteogenic Capacity of Human Adipose-Derived Stromal Cells
Chung, Michael T.; Liu, Chunjun; Hyun, Jeong S.; Lo, David D.; Montoro, Daniel T.; Hasegawa, Masakazu; Li, Shuli; Sorkin, Michael; Rennert, Robert; Keeney, Michael; Yang, Fan; Quarto, Natalina; Longaker, Michael T.
2013-01-01
Background Stem cell-based bone tissue engineering with adipose-derived stromal cells (ASCs) has shown great promise for revolutionizing treatment of large bone deficits. However, there is still a lack of consensus on cell surface markers identifying osteoprogenitors. Fluorescence-activated cell sorting has identified a subpopulation of CD105low cells with enhanced osteogenic differentiation. The purpose of the present study was to compare the ability of CD90 (Thy-1) to identify osteoprogenitors relative to CD105. Methods Unsorted cells, CD90+, CD90−, CD105high, and CD105low cells were treated with an osteogenic differentiation medium. For evaluation of in vitro osteogenesis, alkaline phosphatase (ALP) staining and alizarin red staining were performed at 7 days and 14 days, respectively. RNA was harvested after 7 and 14 days of differentiation, and osteogenic gene expression was examined by quantitative real-time polymerase chain reaction. For evaluation of in vivo osteogenesis, critical-sized (4-mm) calvarial defects in nude mice were treated with the hydroxyapatite-poly(lactic-co-glycolic acid) scaffold seeded with the above-mentioned subpopulations. Healing was followed using micro-CT scans for 8 weeks. Calvaria were harvested at 8 weeks postoperatively, and sections were stained with Movat's Pentachrome. Results Transcriptional analysis revealed that the CD90+ subpopulation was enriched for a more osteogenic subtype relative to the CD105low subpopulation. Staining at day 7 for ALP was greatest in the CD90+ cells, followed by the CD105low cells. Staining at day 14 for alizarin red demonstrated the greatest amount of mineralized extracellular matrix in the CD90+ cells, again followed by the CD105low cells. Quantification of in vivo healing at 2, 4, 6, and 8weeks postoperatively demonstrated increased bone formation in defects treated with CD90+ ASCs relative to all other groups. On Movat's Pentachrome-stained sections, defects treated with CD90+ cells showed the most robust bony regeneration. Defects treated with CD90− cells, CD105high cells, and CD105low cells demonstrated some bone formation, but to a lesser degree when compared with the CD90+ group. Conclusions While CD105low cells have previously been shown to possess an enhanced osteogenic potential, we found that CD90+ cells are more capable of forming bone both in vitro and in vivo. These data therefore suggest that CD90 may be a more effective marker than CD105 to isolate a highly osteogenic subpopulation for bone tissue engineering. PMID:23216074
Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas D; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Eilber, Ursula; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; deFazio, Anna; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J
2017-01-01
Importance Cytotoxic CD8+ T lymphocytes (TILs) participate in immune control of ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design Prospective survival cohort. Setting Multi-center observational. Participants Over 5,500 patients, including 3,196 high-grade serous ovarian carcinomas (HGSOCs), followed prospectively for over 24,650 person-years. Exposure(s) Following immunohistochemistry, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1–2), moderate (3–19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcome Measure(s) Overall survival time. Results Among the five major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (p-trend=4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors which drive infiltration will be key to unravelling outcome heterogeneity in this cancer. PMID:29049607
Peled, A; Kollet, O; Ponomaryov, T; Petit, I; Franitza, S; Grabovsky, V; Slav, M M; Nagler, A; Lider, O; Alon, R; Zipori, D; Lapidot, T
2000-06-01
Hematopoietic stem cell homing and engraftment require several adhesion interactions, which are not fully understood. Engraftment of nonobese/severe combined immunodeficiency (NOD/SCID) mice by human stem cells is dependent on the major integrins very late activation antigen-4 (VLA-4); VLA-5; and to a lesser degree, lymphocyte function associated antigen-1 (LFA-1). Treatment of human CD34(+) cells with antibodies to either VLA-4 or VLA-5 prevented engraftment, and treatment with anti-LFA-1 antibodies significantly reduced the levels of engraftment. Activation of CD34(+) cells, which bear the chemokine receptor CXCR4, with stromal derived factor 1 (SDF-1) led to firm adhesion and transendothelial migration, which was dependent on LFA-1/ICAM-1 (intracellular adhesion molecule-1) and VLA-4/VCAM-1 (vascular adhesion molecule-1). Furthermore, SDF-1-induced polarization and extravasation of CD34(+)/CXCR4(+) cells through the extracellular matrix underlining the endothelium was dependent on both VLA-4 and VLA-5. Our results demonstrate that repopulating human stem cells functionally express LFA-1, VLA-4, and VLA-5. Furthermore, this study implies a novel approach to further advance clinical transplantation.
Badie, B; Schartner, J M; Paul, J; Bartley, B A; Vorpahl, J; Preston, J K
2000-10-01
Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model. Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD 11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c-highly positive, CD45-slightly positive cell), macrophage (CD11b/c-highly positive, CD45-highly positive cell), lymphocyte (CD11b/c-negative, CD45-highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry. Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 +/- 3% and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42). Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.
Numerical modelling of CIGS/CdS solar cell
NASA Astrophysics Data System (ADS)
Devi, Nisha; Aziz, Anver; Datta, Shouvik
2018-05-01
In this work, we design and analyze the Cu(In,Ga)Se2 (CIGS) solar cell using simulation software "Solar Cell Capacitance Simulator in One Dimension (SCAPS-1D)". The conventional CIGS solar cell uses various layers, like intrinsic ZnO/Aluminium doped ZnO as transparent oxide, antireflection layer MgF2, and electron back reflection (EBR) layer at CIGS/Mo interface for good power conversion efficiency. We replace this conventional model by a simple model which is easy to fabricate and also reduces the cost of this cell because of use of lesser materials. The new designed model of CIGS solar cell is ITO/CIGS/OVC/CdS/Metal contact, where OVC is ordered vacancy compound. From this simple structure, even at very low illumination we are getting good results. We simulate this CIGS solar cell model by varying various physical parameters of CIGS like thickness, carrier density, band gap and temperature.
Xie, Yan; Luo, Hongji; Du, Zhimin; Hu, Longxing; Fu, Jinmin
2014-12-01
Phytoremediation utilizing plants and microbes has been increasingly adopted as a green technology for cleaning up heavy metal polluted soils. Cd polluted soil and native bermudagrass from Liuyang and Zhuzhou in Hunan province of China were collected to investigate microbial diversity and isolate Cd resistant fungi, and then to determine the effect of Cd resistant fungi on Cd tolerance and transportation of bermudagrass. The functional diversity of microorganisms was evaluated using the BIOLOG Eco method. Cd-resistant fungi strain was isolated and identified as Aspergillus aculeatus based on the ribosomal internal transcribed spacer region sequence analysis. Bermudagrass was exposed to control, Cd only, and Cd plus A. aculeatus (Cd + A. aculeatus) with growth matrix (sawdust/sand = 3/1 in volume). Results indicated that Cd + A. aculeatus treated bermudagrass exhibited a higher photosynthetic activity compared to Cd only treated plants. Inoculation of A. aculeatus resulted in a decrease in stem and leaf Cd concentrations, to a greater extent for Cd-sensitive than for Cd-tolerant genotype. However, inoculation of A. aculeatus increased root Cd concentration under Cd stress conditions, significantly elevated soil pH, and decreased soil water-soluble Cd concentration. These results suggested that A. aculeatus might be potentially applied to improve Cd tolerance and to reduce Cd transportation to shoot of bermudagrass.
Besser, J.M.; Brumbaugh, W.G.; May, T.W.; Ingersoll, C.G.
2003-01-01
We evaluated the partitioning and toxicity of cadmium (Cd) and copper (Cu) spiked into formulated sediments containing two types of organic matter (OM), i.e., cellulose and humus. Amendments of cellulose up to 12.5% total organic carbon (TOC) did not affect partitioning of Cd or Cu between sediment and pore water and did not significantly affect the toxicity of spiked sediments in acute toxicity tests with the amphipod Hyalella azteca. In contrast, amendments of natural humus shifted the partitioning of both Cd and Cu toward greater concentrations in sediment and lesser concentrations in pore water and significantly reduced toxic effects of both metals. Thresholds for toxicity, based on measured metal concentrations in whole sediment, were greater for both Cd and Cu in sediments amended with a low level of humus (2.9% TOC) than in sediments without added OM. Amendments with a high level of humus (8.9% TOC) eliminated toxicity at the highest spike concentrations of both metals (sediment concentrations of 12.4 ??g Cd/g and 493 ??g Cu/g). Concentrations of Cd in pore water associated with acute toxicity were similar between sediments with and without humus amendments, suggesting that toxicity of Cd was reduced primarily by sorption to sediment OM. However, toxic effects of Cu in humus treatments were associated with greater pore-water concentrations than in controls, suggesting that toxicity of Cu was reduced both by sorption and by complexation with soluble ligands. Both sorption and complexation by OM tend to make proposed sediment quality guidelines (SQGs) based on total metal concentrations more protective for high-OM sediments. Our results suggest that the predictive ability of SQGs could be improved by models of metal interactions with natural OM in sediment and pore water.
Besser, John M; Brumbaugh, William G; May, Thomas W; Ingersoll, Christopher G
2003-04-01
We evaluated the partitioning and toxicity of cadmium (Cd) and copper (Cu) spiked into formulated sediments containing two types of organic matter (OM), i.e., cellulose and humus. Amendments of cellulose up to 12.5% total organic carbon (TOC) did not affect partitioning of Cd or Cu between sediment and pore water and did not significantly affect the toxicity of spiked sediments in acute toxicity tests with the amphipod Hyalella azteca. In contrast, amendments of natural humus shifted the partitioning of hoth Cd and Cu toward greater concentrations in sediment and lesser concentrations in pore water and significantly reduced toxic effects of both metals. Thresholds for toxicity, based on measured metal concentrations in whole sediment, were greater for both Cd and Cu in sediments amended with a low level of humus (2.9% TOC) than in sediments without added OM. Amendments with a high level of humus (8.9% TOC) eliminated toxicity at the highest spike concentrations of both metals (sediment concentrations of 12.4 microg Cd/g and 493 microg Cu/g). Concentrations of Cd in pore water associated with acute toxicity were similar between sediments with and without humus amendments, suggesting that toxicity of Cd was reduced primarily by sorption to sediment OM. However, toxic effects of Cu in humus treatments were associated with greater pore-water concentrations than in controls, suggesting that toxicity of Cu was reduced both by sorption and by complexation with soluble ligands. Both sorption and complexation by OM tend to make proposed sediment quality guidelines (SQGs) based on total metal concentrations more protective for high-OM sediments. Our results suggest that the predictive ability of SQGs could be improved by models of metal interactions with natural OM in sediment and pore water.
1981-07-10
Pohlmann, L. D. Some models of observer behavior in two-channel auditory signal detection. Perception and Psychophy- sics, 1973, 14, 101-109. Spelke...spatial), and processing modalities ( auditory versus visual input, vocal versus manual response). If validated, this configuration has both theoretical...conclusion that auditory and visual processes will compete, as will spatial and verbal (albeit to a lesser extent than auditory - auditory , visual-visual
Differential scanning calorimetry of coal
NASA Technical Reports Server (NTRS)
Gold, P. I.
1978-01-01
Differential scanning calorimetry studies performed during the first year of this project demonstrated the occurrence of exothermic reactions associated with the production of volatile matter in or near the plastic region. The temperature and magnitude of the exothermic peak were observed to be strongly affected by the heating rate, sample mass and, to a lesser extent, by sample particle size. Thermal properties also were found to be influenced by oxidation of the coal sample due to weathering effects.
A Call to Service for America’s Youth
2011-03-24
single- parent head of households, an ineffective public education system and to a lesser extent, having both parents working and unable to supervise...Carlisle Barracks, PA 17013-5050 USAWC CLASS OF 2011 The U.S. Army War College is accredited by the Commission on Higher Education of the...Middle State Association of Colleges and Schools, 3624 Market Street, Philadelphia, PA 19104, (215) 662-5606. The Commission on Higher Education is an
Cytochemical Organization of the Retino-Suprachiasmatic System
1994-03-11
strongly expiessed of the, non-NMDA ionotropic receptors . Other AMPA-preferring receptors , GluR3 and -R4, were also found, but to lesser extent...kainate, and NMDA receptor RN was found in the hypothalamus. GluRi and GluR2 were ang the nmst strongly expressed of the non-NvDA ionotropic receptors ...several different glutamate receptors . The expression of many different types of ionotropic glutamate receptors throughout the hypothalamus suggests that
Interdisciplinary Study on Advanced NDI Techniques.
1980-01-01
treatment , etc. Their presence in manufactured components plays an important role in determining the behavior of the component when it is subjected...Table (3.1) and (3.2) have shown that this quantity differs considerably with heat treatment , and to a lesser extent from one specimen to the other...These differences are mainly due to the variations of inter- nal stresses in specimens, even when they are given the same heat treatment . Published data
2008-10-01
Fresh whole blood D Not available D Trigger: D Treatment protocol: Comment: Adjuvant therapy D Aprotinin D Tranexamic acid D Desmopressin D Ca...that were mentioned included prothrombin complex concentrate (PCC), activated recombinant factor VII (rFVIIa), aprotinin, and tranexamic acid (Fig. 2...of respondents, followed by Ca (53%) and vitamin K (38%), and to a lesser extent tranexamic acid (28%), aprotinin (26%), desmopressin (24%), and
Rhodium complexes as therapeutic agents.
Ma, Dik-Lung; Wang, Modi; Mao, Zhifeng; Yang, Chao; Ng, Chan-Tat; Leung, Chung-Hang
2016-02-21
The landscape of inorganic medicinal chemistry has been dominated by the investigation of platinum, and to a lesser extent ruthenium, complexes over the past few decades. Recently, complexes based on other metal centers such as rhodium have attracted attention due to their tunable chemical and biological properties as well as distinct mechanisms of action. This perspective highlights recent examples of rhodium complexes that show diverse biological activities against various targets, including enzymes and protein-protein interactions.
Democratization in the Arab World: A Summary of Lessons from Around the Globe
2013-01-01
key’s democratization experience together with several southern European cases . Democratization in the Arab World: A Summary of Lessons 3 termed the...examined democratization patterns in each of the following regions and focused in-depth on the cases noted in parentheses: South- ern Europe (Portugal...quickly, while in Turkey progress was more halting. In the Portuguese, Greek, and Spanish cases and, to a lesser extent, later in Turkey, the pull
Goto, Keisuke
2016-10-01
CD138 (syndecan-1) immunoexpression has been reported to be specific for the plasmacytoid variant of urothelial carcinomas (UCs). The aim of this study was to examine the utility of CD138 immunohistochemistry for diagnosing the plasmacytoid variant of UCs. The extent and intensity of CD138 immunostaining were evaluated in 22 infiltrating UCs, 2 other infiltrating carcinomas, 15 noninvasive urothelial lesions, 3 other benign lesions, and perilesional normal tissues. CD138 immunostaining of the normal urothelial epithelium was universally diffuse and strong. In addition, all 42 cases of urinary tract lesions exhibited positive CD138 immunostaining; however, 1 of 3 plasmacytoid variants exhibited focal CD138 expression. The frequency of CD138 positivity in plasmacytoid variants may be relatively low, compared with that observed in the conventional types and other variants; thus, it is not appropriate to assume that CD138 expression in UCs is specific for plasmacytoid variants. © The Author(s) 2016.
Zhu, Lei; Jia, Yong-gang; Pan, Yu-ying
2013-09-01
The determination of pollution extent and health risk assessment are the premise of heavy metal contaminated site remediation. The content of Cu, Cr, Pb, Cd, Zn, Ni in Qingdao North Station was detected, and the correlation of the 6 kinds of heavy metal content was analyzed. The pollution extent in excess of background values was characterized by anthropogenic influence multiple, and the pollution of heavy metal in soil was evaluated using geoaccumulation index and a new method which connects geoaccumulation index with Nemero index. Finally, human health risk assessment was carried out with health risk assessment model for heavy metal content. The results showed that Qingdao North Station soil were polluted by heavy metals. Six heavy metal pollution levels were: Cd > Cu > Ni > Pb > Cr > Zn, and Cd had reached the severity pollution level, Cu and Ni followed by, Cr, Pb and Zn were in minor pollution level. The order of coefficient variation in all heavy metals was: Cd > Ni > Cr > Zn > Pb > Cu. Within the study area soil heavy metal distribution was different, but overall discrepancy was small. The order of non-cancer hazards of heavy metals in soil was Cr > Pb > Cu > Ni > Cd > Zn, and the order of carcinogen risks of heavy metals was Ni > Cd. The non-cancer hazard and carcinogen risks values of metals were both lower than that their threshold values. They were not the direct threats to human health.
Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue
NASA Technical Reports Server (NTRS)
Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.
2003-01-01
HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.
Trace elements in urban and suburban rainfall, Mersin, Northeastern Mediterranean
NASA Astrophysics Data System (ADS)
Özsoy, Türkan; Örnektekin, Sermin
2009-10-01
Spatial/temporal variabilities of rainwater constituents are examined based on soluble/insoluble trace elements, pH and electrical conductivity measurements in rainfall sampled during December 2003-May 2005 at two urban and two suburban sites in Mersin, an industrialized city of 850,000 inhabitants on the southern coast of Turkey. In the analyses, backward air mass trajectories for rainy days were used in addition to factor analyses, enrichment factors, phase distributions and correlations between trace elements. The pH varied from 4.8 to 8.5 with an average value of 6.2, reflecting a mainly alkaline regime. Mean concentrations of trace elements collected from urban and suburban sites are spatially variable. Based on the overall data, total concentrations of trace elements were ordered as Ca > Na > Fe > Al > Mg > K > Zn > Mn > Sr > Pb > Ni > Cr > Ba > Cu > Co > Cd. Mainly terrigeneous (Ca, Fe, Al) and, to a lesser extent, sea salt particles (Na, Mg) were shown to be the major source of trace elements. Excluding major cations, the solubilities of trace elements were found to be ordered as Sr > Zn > Ba > Mn > Cu > Ni > Cr > Fe > Al, confirming the lower solubility of crustal elements. Cd, Co and Pb were excluded from the above evaluation because of the low numbers of soluble samples allowing quantitative measurements. The solubilities of Al, Fe, Mn and particularly of Ni were found to be considerably lower than those reported for various sites around the world, most likely due to the effect of pH. During the entire sampling period, a total of 28 dust transport episodes associated with 31 red rain events were identified. Extremely high mean concentration ratios of Al (8.2), Fe (14.4) and Mn (13.1) were observed in red rain, compared to normal rain. The degree of this enhancement displayed a decrease from crustal to anthropogenic origin elements and the lowest enhancements were found for anthropogenic origin elements of Zn and Cd (both having a ratio of 1.1). Aerosol dust was found to be the main source of almost all analyzed elements in Mersin precipitation, regardless that they are crustal or anthropic derived elements. The magnitude of crustal source contribution to trace element budget of precipitation was at its highest levels for crustal originated elements, most probably due to much higher scavenging ratios of crustal elements compared to anthropogenic ones.
Neri, L M; Bortul, R; Zweyer, M; Tabellini, G; Borgatti, P; Marchisio, M; Bareggi, R; Capitani, S; Martelli, A M
1999-06-01
The higher order of chromatin organization is thought to be determined by the nuclear matrix, a mainly proteinaceous structure that would act as a nucleoskeleton. The matrix is obtained from isolated nuclei by a series of extraction steps involving the use of high salt and nonspecific nucleases, which remove chromatin and other loosely bound components. It is currently under debate whether these structures, isolated in vitro by unphysiological extraction buffers, correspond to a nucleoskeleton existing in vivo. In most cell types investigated, the nuclear matrix does not spontaneously resist these extractions steps; rather, it must be stabilized before the application of extracting agents. In this study nuclei, isolated from K562 human erythroleukemia cells, were stabilized by incubation with different metal ions (Ca2+, Cu2+, Zn2+, Cd2+), and the matrix was obtained by extraction with 2 M NaCl. By means of ultrastructural analysis of the resulting structures, we determined that, except for Ca2+, all the other metals induced a stabilization of the matrix, which retained the inner fibrogranular network and residual nucleoli. The biochemical composition, analyzed by two-dimensional gel electrophoresis separation, exhibited a distinct matrix polypeptide pattern, characteristic of each type of stabilizing ion employed. We also investigated to what extent metal ions could maintain in the final structures the original distribution of three inner matrix components, i.e. NuMA, topoisomerase IIalpha, and RNP. Confocal microscopy analysis showed that only NuMa, and, to a lesser extent, topoisomerase IIalpha, were unaffected by stabilization with divalent ions. On the contrary, the fluorescent RNP patterns detected in the resulting matrices were always disarranged, irrespective of the stabilization procedure. These results indicate that several metal ions are powerful stabilizing agents of the nuclear matrix prepared from K562 erythroleukemia cells and also strengthen the concept that NuMA and topoisomerase IIalpha may act as structural components of the nuclear matrix.
Galatsch, Michael; Li, Jian; Derycke, Hanne; Müller, Bernd Hans; Hasselhorn, Hans Martin
2013-12-05
Previous cross-sectional findings from the European Nurses Early Exit Study (NEXT) show that nurses who were dissatisfied with their work schedule tended to consider leaving the nursing profession. Mediating factors in this decision process may be caused by self-perceived poor work ability and/or health. The aim of this paper is to investigate changes in work ability and general health among nurses in relation to requested, forced and denied change of shift schedule. Longitudinal data from the NEXT Study was used. In total 11,102 nurses from Belgium, Germany, Finland, the Netherlands, Poland, Slovakia, France and Italy completed both the 'basic questionnaire' (t1) and the '12 month follow-up questionnaire' (t2). To examine the time-effect (repeated measures) and the group-effect of five defined groups of nurses on the Work Ability Index (WAI) and general health (SF36), an adjusted 2-way analysis of covariance (ANCOVA) was performed. The nurses who wanted to, but could not change their shifts during the 12 month follow-up had the lowest initial and follow-up scores for WAI (t1: 37.6, t2: 36.6, p <0.001), lowest general health (t1: 63.9, t2: 59.2, p <0.001) and showed the highest decrease in both outcomes. Shift pattern change in line with the nurses' wishes was associated with improved work ability and to a lesser comparatively low extent with increased decline in health scores. A forced change of shift against the nurses' will was significantly associated with a deteriorating work ability and health. The findings would suggest that nurses' desire to change their shift patterns may be an indicator for perceived low work ability and/or low health. The results also indicate that fulfilling nurses' wishes with respect to their shift work pattern may improve their personal resources such as work ability and - to somewhat lesser extent - health. Disregarding nurses' preferences, however, bears the risk for further resource deterioration. The findings imply that shift schedule organization may constitute a valuable preventive tool to promote nurses' work ability and - to lesser extent - their perceived health, not least in aging nursing work forces.
Effects of Beta-blockers on Punished Responding and on Heart Rate in Pigeons
1986-06-17
in pigeons. The present study attempted to confirm that fmding, to compare the effects of propranolol, metoprolol , and atenolol with that of...occurred at approximately 15% iii of the high unpunished response rates. Propranolol, atenolol, and metoprolol doses from 1.0 to 10.0 mg!kg, i.m. and...and, to a somewhat lesser extent, metoprolol produced large dose-related decreases. Atenolol’s effect was small. Chlordiazepoxide increased heart rate
Purification and characterization of a tuliposide-converting enzyme from bulbs of Tulipa gesneriana.
Kato, Yasuo; Shoji, Kazuaki; Ubukata, Makoto; Shigetomi, Kengo; Sato, Yukio; Nakajima, Noriyuki; Ogita, Shinjiro
2009-08-01
An enzyme that catalyzes the stoichiometric conversion of 6-tuliposide into tulipalin was purified and characterized from bulbs of Tulipa gesneriana. The enzyme appeared to be a dimer, the relative molecular mass (Mr) of each subunit being 34,900; it had maximum activity and stability at neutral pH and moderate temperature. The enzyme preferentially acted on such glucose esters as 6-tuliposides, and to a lesser extent on p-nitrophenylacetate.
2000-01-01
tactical support, and, to a lesser extent, bom- bardment. The American Army had to digest quickly the crucial lesson already absorbed by the...2. United States Air Force Statistical Digest , 1947, Director of Statistical Services, Comptroller, HQ USAF, Washington, D.C., 1948, 15-16, 72, 132...Statistical Digest , Director of Statistical Services, Deputy Chief of Staff, Comptroller, HQ USAF, Washington, D.C., Nov 1952, 162-164. 6. Sarah A
Cardiovascular and other dynamic systems in long-term space flight
NASA Technical Reports Server (NTRS)
Tipton, David A.
1987-01-01
The paper examines the physiology of the cardiovascular system, and to a lesser extent the endocrine, renal, and hematopoietic systems. The paper highlights the aspects of these areas that are most pertinent to space manufacturing, i.e., working in space. Areas covered include the physiological costs of working in microgravity and partial gravity (e.g., the moon or Mars), countermeasures to potentially adverse physiological adaptations, and problems associated with return to earth after long periods of weightlessness.
NASA Technical Reports Server (NTRS)
Rice, James E.
1996-01-01
The report is organized into sections representing the phases of work performed in analyzing the STS 62 results and preparing the instrument for STS 65. Section 2 contains a brief analysis of the STS 62 data which verifies the instrument changes to resolve the STS 58 problems. Section 3 describes the results from STS 62, including the original mission plan and several minor calibration period anomalies first discovered on STS 58 and reappearing to a lesser extent on STS 62.
Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles
NASA Astrophysics Data System (ADS)
Zubareva, A. A.; Shcherbinina, T. S.; Varlamov, V. P.; Svirshchevskaya, E. V.
2015-04-01
Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive groups that is easily used to obtain derivatives with a desired charge and hydrophobic properties. The aim of this work was to study the intracellular traffic of positively charged hexanoyl-chitosan (HC) or HC-based nanoparticles (HCNPs) and negatively charged succinoyl-chitosan (SC) and SCNPs in epithelial and macrophage cell lines. By using flow cytometry we demonstrated that positively charged HC adhered to cell membranes quicker and more efficiently than negatively charged SC or NPs. However confocal studies showed that SC and SCNPs penetrated cells much more efficiently than HC while HCNPs did not enter the epithelial cells. Macrophages also phagocyted better negatively charged material but were able to engulf both HC and HCNPs. Upon entering the cells, SC and SCNPs were co-localized with endosomes and lysosomes while HC was found in mitochondria and, to a lesser extent, in lysosomes of epithelial cells. Macrophages, RAW264.7, more efficiently transported all Chi samples to the lysosomal compartment while some positively charged material was still found in mitochondria. Incubation of Chi derivatives and ChiNPs at pH specific to mitochondria (8.0) and lysosomes (4.5) demonstrated the neutralization of Chi charge. We concluded that epithelial cells and, to a lesser extent, macrophages sort charged material to the organelles neutralizing Chi charge.
Cosh, Suzanne; Hawkins, Kimberley; Skaczkowski, Gemma; Copley, David; Bowden, Jacqueline
2015-01-01
Smoking prevalence among Aboriginal Australian young people greatly exceeds the prevalence in the broader population of Australian young people, yet limited research has explored the social context in which young Aboriginal Australians smoke. Four focus groups were conducted in 2009 with South Australian Aboriginal smokers aged 15-29 years residing in urban areas (n = 32) to examine attitudes and experiences surrounding smoking and quitting. The primary reasons for smoking initiation and maintenance among Aboriginal Australian young people were identified as stress, social influence and boredom. Motivators for quitting were identified as pregnancy and/or children, sporting performance (males only), cost issues and, to a lesser extent, health reasons. The barriers to cessation were identified as social influence, the perception of quitting as a distant event and reluctance to access cessation support. However, it appears that social influences and stress were particularly salient contributors to smoking maintenance among Aboriginal Australian young people. Smoking cessation interventions targeted at young urban Aboriginal Australian smokers should aim to build motivation to quit by utilising the motivators of pregnancy and/or children, sporting performance (males only), cost issues and, to a lesser extent, health reasons, while acknowledging the pertinent role of social influence and stress in the lives of young urban Aboriginal Australian smokers.
Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study.
Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer
2015-01-01
We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders.
Xu, Ruqiang; El-Hage, Nazira; Dever, Seth M
2015-11-01
HIV penetrates the central nervous system (CNS), and although it is clear that microglia and to a lesser extent astrocytes are infected, whether certain other cell types such as neurons are infected remains unclear. Here, we confirmed the finding that RNAs of both cellular and viral origins are present in native HIV-1 particles and exploited this phenomenon to directly examine HIV-1 infectivity of CNS cell types. Using in vitro transcribed mRNAs that were labeled with a fluorescent dye, we showed that these fluorescent mRNAs were packaged into HIV-1 particles by directly examining infected cells using fluorescence microscopy. Cells in culture infected with these labeled virions showed the fluorescent signals of mRNA labels by a distinct pattern of punctate, focal signals within the cells which was used to demonstrate that the CXCR4-tropic NL4-3 strain was able to enter microglia and to a lesser extent astrocytes, but not neurons. The strategy used in the present study may represent a novel approach of simplicity, robustness and reliability for versatile applications in HIV studies, such as the determination of infectivity across a broad range of cell types and within sub-populations of an individual cell type by direct visualization of viral entry into cells. Copyright © 2015 Elsevier B.V. All rights reserved.
Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study
Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer
2015-01-01
PURPOSE We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. METHODS This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. RESULTS In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. CONCLUSION A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders. PMID:25835077
Oberg, Katarina; Sjögren Fugl-Meyer, Kerstin
2005-03-01
To explore the associations between women's distressing sexual dysfunctions and different aspects of life satisfaction together with women's concomitant socio-psychological characteristics. Thus, this descriptive article does not discuss causalities. A nationally representative sample of sexually active Swedish women aged 18-65 years in a heterosexual steady partner relationship participated in 1996 in a combined structured interview/questionnaire investigation. Personal sexual distress caused by low sexual interest, insufficient lubrication, orgasm dysfunction, dyspareunia, and vaginism was classified as manifest and mild. Concomitant conditions explored were perceived health, stability of domestic situation, perception of male partner's sexual functions/dysfunctions per se, and some socio-demographic factors. Satisfaction with life as a whole and with 10 different domains of life were reported by using the LiSat-11 checklist. Main results were that a multitude of the independent variables were univariately associated with manifest and, to a lesser extent, mild distressing sexual dysfunctions. This was particularly true for satisfaction with partner relationship and for male's sexual dysfunctions. By performing multiple logistic regressions, the numbers were markedly reduced. The resulting statistical models still contained sexual partner's sexual dysfunctions and satisfaction with partner relationship as dominant covariants of most distressing sexual dysfunctions. Reported low level of satisfaction with partner relationship and male sexual dysfunctions per se are likely to co-occur with manifest but, to a lesser extent, mild distressing sexual dysfunctions in Swedish women aged 18-65 years.
Jaleco, A C; Covas, M J; Pinto, L A; Victorino, R M
1994-12-01
Some clinical studies indicate that disease progression in HIV-2-infected subjects may be slower than in HIV-1. We investigated whether there were differences in the distribution of CD45RO+ (memory) and CD45RA+ (naive) T-cell subsets between HIV-1 and HIV-2 infection. Analysis of lymphocyte subsets was performed by flow cytometry in peripheral blood mononuclear cells from healthy controls, HIV-1-(n = 49) and HIV-2-infected (n = 47) individuals divided into two groups: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL) and AIDS-related complex (ARC)/AIDS. Both HIV-1- and HIV-2-infected patients had significant reductions in the absolute number and percentage of CD4+ lymphocytes compared with seronegative individuals. No significant differences were found between HIV-2- and HIV-1-infected subjects in the same clinical stage. CD4+CD45RA+ cells were significantly reduced in HIV-1 and HIV-2 ARC/AIDS patients and mildly reduced in ASY/PGL HIV-1 and HIV-2 patients. There were no differences in the degree of reduction of CD4+CD45RO+ cells in ASY/PGL HIV-1 versus HIV-2 patients. However, in HIV-1-infected ARC/AIDS individuals the reduction in the percentage of this subset was more pronounced than in HIV-2 infection and this difference reached statistical significance. The increase in CD8+ lymphocytes (percentage and absolute number) was more pronounced in HIV-1 and the differences between HIV-1- and HIV-2-infected patients were statistically significant. CD8+CD45RO+ cells were significantly increased both in ASY/PGL and ARC/AIDS HIV-1-infected patients, whereas HIV-2-infected ASY/PGL patients had normal levels of these cells and HIV-2-infected ARC/AIDS patients had increases that were much less pronounced than that observed in HIV-1-infected ARC/AIDS patients. Significant differences in the absolute number and percentage of this subset between HIV-1- and HIV-2-infected individuals in similar clinical stages were found. HIV-2-infected individuals exhibit a lesser degree of depletion of memory CD4+ cells and a more limited expansion of CD8+CD45RO+ subset, which could be related to the putative lower immunopathogenicity of HIV-2.
Cheng, Jiaji; Hao, Junjie; Liu, Haochen; Li, Jiagen; Li, Junzi; Zhu, Xi; Lin, Xiaodong; Wang, Kai; He, Tingchao
2018-05-30
Ligand-induced chirality in semiconductor nanocrystals (NCs) has attracted attention because of the tunable optical properties of the NCs. Induced circular dichroism (CD) has been observed in CdX (X = S, Se, Te) NCs and their hybrids, but circularly polarized luminescence (CPL) in these fluorescent nanomaterials has been seldom reported. Herein, we describe the successful preparation of l- and d-cysteine-capped CdSe-dot/CdS-rods (DRs) with tunable CD and CPL behaviors and a maximum anisotropic factor ( g lum ) of 4.66 × 10 -4 . The observed CD and CPL activities are sensitive to the relative absorption ratio of the CdS shell to the CdSe core, suggesting that the anisotropic g-factors in both CD and CPL increase to some extent for a smaller shell-to-core absorption ratio. In addition, the molar ratio of chiral cysteine to the DRs is investigated. Instead of enhancing the chiral interactions between the chiral molecules and DRs, an excess of cysteine molecules in aqueous solution inhibits both the CD and CPL activities. Such chiral and emissive NCs provide an ideal platform for the rational design of semiconductor nanomaterials with chiroptical properties.
Jaudszus, Anke; Gruen, Michael; Watzl, Bernhard; Ness, Christina; Roth, Alexander; Lochner, Alfred; Barz, Dagmar; Gabriel, Holger; Rothe, Michael; Jahreis, Gerhard
2013-01-01
Despite their beneficial anti-inflammatory properties, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may increase the infection risk at high doses, likely by generating an immune-depressed state. To assess the contribution of different immune cell populations to the immunomodulatory fatty acid effect, we comparatively investigated several aspects of inflammation in human T-helper (Th) cells and monocytes. Both fatty acids, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of cytokine-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells. In monocytes, both EPA and DHA increased interleukin (IL)-10 without affecting tumor necrosis factor (TNF)-α and IL-6. Cellular incorporation of EPA and DHA occurred mainly at the expense of arachidonic acid. Concomitantly, thromboxane B (TXB)2 and leukotriene B (LTB)4 in supernatants decreased, while levels of TXB3 and LTB5 increased. This increase was independent of activation and in accordance with cyclooxygenase expression patterns in monocytes. Moreover, EPA and DHA gave rise to a variety of mono- and trihydroxy derivatives of highly anti-inflammatory potential, such as resolvins and their precursors. Our results suggest that EPA and DHA do not generally affect immune cell functions in an inhibitory manner but rather promote pro-resolving responses. PMID:23349208
Austruy, A; Wanat, N; Moussard, C; Vernay, P; Joussein, E; Ledoigt, G; Hitmi, A
2013-04-01
In order to revegetate an industrial soil polluted by trace metals and metalloids (As, Pb, Cu, Cd, Sb), the impact of pollution on three plant species, Solanum nigrum and Agrostis capillaris, both native species in an industrial site, and Vicia faba, a plant model species, is studied. Following the study of soil pollution from the industrial wasteland of Auzon, it appears that the As is the principal pollutant. Particular attention is given to this metalloid, both in its content and its speciation in the soil that the level of its accumulation in plants. In V. faba and A. capillaris, the trace metals and metalloids inhibit the biomass production and involve a lipid peroxidation in the leaves. Furthermore, these pollutants cause a photosynthesis perturbation by stomatal limitations and a dysfunction of photosystem II. Whatever the plant, the As content is less than 0.1 percent of dry matter, the majority of As absorbed is stored in the roots which play the role of trap organ. In parallel, the culture of S. nigrum decreases significantly the exchangeable and weakly adsorbed fraction of As in rhizospheric soil. This study has highlighted the ability of tolerance to trace metals of S. nigrum and to a lesser extent A. capillaris. Our data indicate that V. faba is not tolerant to soil pollution and is not a metallophyte species. Copyright © 2012 Elsevier Inc. All rights reserved.
Sodium chloride inhibits IFN-γ, but not IL-4, production by invariant NKT cells.
Jeong, Dongjin; Kim, Hye Young; Chung, Doo Hyun
2018-01-01
Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like functions in vivo by producing IFN-γ and IL-4. Sodium chloride modulates the functions of various immune cells, including conventional CD4 + T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN-γ, but not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18) stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR engagement or IL-12 + IL-18. Sodium chloride increased phosphorylated p38 expression in iNKT cells and inhibitors of p38, NFAT5, SGK1, and TCF-1 restored IFN-γ production by iNKT cells stimulated with sodium chloride and TCR engagement. Furthermore, adoptive transfer of iNKT cells pretreated with sodium chloride restored antibody-induced joint inflammation to a lesser extent than for untreated iNKT cells in Jα18 knockout mice. These findings suggest that sodium chloride inhibits IFN-γ production by iNKT cells in TCR-dependent and TCR-independent manners, which is dependent on p38, NFAT5, SGK1, and TCF-1. These findings highlight the functional role of sodium chloride in iNKT cell-mediated inflammatory diseases. ©2017 Society for Leukocyte Biology.
Woodward, Daniel F.; Goldstein, Jack N.; Farag, Aïda M.; Brumbaugh, William G.
1997-01-01
The South Fork basin of the Coeur d'Alene River, Idaho has been an area of heavy mining activity since the 1880s. The mining operations have resulted in elevated concentrations of metals in surface water, most notably cadmium, lead, zinc, and, to a lesser extent, copper. The metals affected surface water quality downstream in the Coeur d'Alene basin and are suspected to be one of the primary reasons for the reduction in populations of native westslope cutthroat trout Oncorhynchus clarki lewisi. The avoidance response of a surrogate species, Snake River cutthroat trout O. clarki (unnamed subspecies), was evaluated against conditions simulating those in the Coeur d'Alene River basin. Cutthroat trout avoided a metals mixture of these concentrations: Cd (0.30 ??g/L), Cu (6.0 ??g/L), Pb (0.6 ??g/L), and Zn (28 ??g/L). The avoidance response to either Cu or Zn alone was similar to the avoidance response to the mixture, suggesting that avoidance to the mixture was due to these metals. After acclimation to Zn at 55 ??g/L for 90 d, cutthroat trout detected and preferred a lower Zn concentration of 28 ??g/L. The lowest Zn concentrations avoided (28 ??g/L) were 1/6 to 1/78 the Zn concentrations measured in the South Fork and lower Coeur d'Alene River basins. Avoidance of metals-contaminated habitats by cutthroat trout may be, in part, responsible for reduced fish populations.
Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia
Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.
2012-01-01
While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4+ T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT. PMID:22205732
Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Ursula, Eilber; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; Anna, deFazio; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J
2017-12-01
Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Overall survival time. The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.
NASA Technical Reports Server (NTRS)
Ueno, Akiko; Vannais, Diane; Lenarczyk, Marek; Waldren, Charles A.; Chatterjee, A. (Principal Investigator)
2002-01-01
It has been reported that X-ray induced HPRT- mutation in cultured human cells is prevented by ascorbate added after irradiation. Mutation extinction is attributed to neutralization by ascorbate, of radiation-induced long-lived radicals (LLR) with half-lives of several hours. We here show that post-irradiation treatment with ascorbate (5 mM added 30 min after radiation) reduces, but does not eliminate, the induction of CD59- mutants in human-hamster hybrid A(L) cells exposed to high-LET carbon ions (LET of 100 KeV/microm). RibCys, [2(R,S)-D-ribo-1',2',3',4'-Tetrahydroxybutyl]-thiazolidene-4(R)-ca riboxylic acid] (4 mM) gave a similar but lesser effect. The lethality of the carbon ions was not altered by these chemicals. Preliminary data are presented that ascorbate also alters the spectrum of CD59- mutations induced by the carbon beam, mainly by reducing the incidence of small mutations and mutants displaying transmissible genomic instability (TGI), while large mutations are unaffected. Our results suggest that LLR are important in initiating TGI.
Oyler-McCance, Sara J.; DeYoung, Randall W; Fike, Jennifer; Hagen, Christian A.; Johnson, Jeff A.; Larsson, Lena C.; Patten, Michael
2016-01-01
The distribution of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) has been markedly reduced due to loss and fragmentation of habitat. Portions of the historical range, however, have been recolonized and even expanded due to planting of conservation reserve program (CRP) fields that provide favorable vegetation structure for Lesser Prairie-Chickens. The source population(s) feeding the range expansion is unknown, yet has resulted in overlap between Lesser and Greater Prairie-Chickens (T. cupido) increasing the potential for hybridization. Our objectives were to characterize connectivity and genetic diversity among populations, identify source population(s) of recent range expansion, and examine hybridization with the Greater Prairie-Chicken. We analyzed 640 samples from across the range using 13 microsatellites. We identified three to four populations corresponding largely to ecoregions. The Shinnery Oak Prairie and Sand Sagebrush Prairie represented genetically distinct populations (F ST > 0.034 and F ST > 0.023 respectively). The Shortgrass/CRP Mosaic and Mixed Grass ecoregions appeared admixed (F ST = 0.009). Genetic diversity was similar among ecoregions and N e ranged from 142 (95 % CI 99–236) for the Shortgrass/CRP Mosaic to 296 (95 % CI 233–396) in the Mixed Grass Prairie. No recent migration was detected among ecoregions, except asymmetric dispersal from both the Mixed Grass Prairie and to a lesser extent the Sand Sagebrush Prairie north into adjacent Shortgrass/CRP Mosaic (m = 0.207, 95 % CI 0.116–0.298, m = 0.097, 95 % CI 0.010–0.183, respectively). Indices investigating potential hybridization in the Shortgrass/CRP Mosaic revealed that six of the 13 individuals with hybrid phenotypes were significantly admixed suggesting hybridization. Continued monitoring of diversity within and among ecoregions is warranted as are actions promoting genetic connectivity and range expansion.
Li, Peng; Fu, Jian-hua; Li, Xin-zhi
2008-08-01
To study the effect and molecular mechanism of two haw leaf extracts, Vitexin-rhamnoside (VR) and Vitexin-glucoside (VG), and their preparation, Aoshaen injection (AI), on the polymorphonuclear leucocyte (PMN) adhesion during human umbilical vein endothelial cell (HUVEC) anoxia/reoxygenation (A/R) injury. The cell model of A/R injury duplicated by breaking off the oxygen supplying of HUVEC for 60 min followed with reoxygenating for 30 min (phase 1) or 240 min (phase 2) was taken as the experimental objective. The effects of testing drugs (VR, VG and AI) on PMN adhesion in the model cells were measured by enzyme immunoassay, and their effects on PMN superficial adhesion molecule CD11/CD18 expression were measured by flow cytometer respectively. After 60 min of anoxia, HUVEC was shrunk and deformed. The adhesion between PMN and HUVEC significantly revealed at phase 1 in the model group, but it was fewer in the normal cell group, and also lesser in the groups treated with various drugs. The condition of cell adhesion revealed at phase 2 was the similar to that at phase 1. All testing drugs, VR, VG and AI, showed inhibitory effect on the cell adhesion at either phase 1 or phase 2, showing a certain dose-effect relationship. The expression of CD11/ CD18 was also inhibited by the testing drugs, and a good dose-effect relation was shown by VG and AI. At the resting condition, there are almost no expression of CD11/CD18 molecule, but it could be enhanced by incubating PMN with supernate of A/R injured HUVEC culture, and more marked at phase 1. Adding the test drugs into the supernate could inhibit the enhancing of CD11/CD18 molecule expression and reduce the PMN-HUVEC adhesion, which may be one of the molecular mechanisms of haw leaf extracts and their preparation in protecting heart against A/R injury.
Mittal, Ravinder K; Zifan, Ali; Kumar, Dushyant; Ledgerwood-Lee, Melissa; Ruppert, Erika; Ghahremani, Gary
2017-09-01
The smooth muscles of the lower esophageal sphincter (LES) and skeletal muscles of the crural diaphragm (CD) provide a closure/antireflux barrier mechanism at the esophago-gastric junction (EGJ). A number of questions in regard to the pressure profile of the LES and CD remain unclear, e.g., 1 ) Why is the LES pressure profile circumferentially asymmetric, 2 ) Is the crural diaphragm (CD) contraction also circumferentially asymmetric, and 3 ) Where is the LES and CD pressure profile located in the anatomy of the esophagus and stomach? The three-dimensional (3-D) high-resolution esophageal manometry (HRM) catheter can record a detailed profile of the EGJ pressure; however, it does not allow the determination of the circumferential orientation of individual pressure transducers in vivo. We used computed tomography (CT) scan imaging in combination with 3-D EGJ pressure recordings to determine the functional morphology of the LES and CD and its relationship to the EGJ anatomy. A 3-D-HRM catheter with 96 transducers (12 rings, 7.5 mm apart, located over 9-cm length of the catheter, with eight transducers in each ring, 45° apart (Medtronics), was used to record the EGJ pressure in 10 healthy subjects. A 0.5-mm diameter metal ball (BB) was taped to the catheter, adjacent to transducer 1 of the catheter. The EGJ was recorded under the following conditions: 1 ) end-expiration (LES pressure) before swallow, after swallow, and after edrophonium hydrochloride; and 2 ) peak inspiration (crural diaphragm contraction) for tidal inspiration and forced maximal inspiration. A CT scan was performed to localize the circumferential orientation of the BB. The CT scan imaging allowed the determination of the circumferential orientation of the LES and CD pressure profiles. The LES pressure under the three end-expiration conditions were different; however, the shape of the pressure profile was unique with the LES length longer toward the lesser curvature of the stomach as compared with the greater curvature. The pressure profile revealed circular and axial pressure asymmetry, with greatest pressure and shortest cranio-caudal length on the left (close to the angle of His). The CD contraction with tidal and forced inspiration increases pressure in the cranial half of the LES pressure profile, and it was placed horizontally across the recording. The CD, esophagus, and stomach were outlined in the CT scan images to construct a 3-D anatomy of the region; it revealed that the hiatus (CD) is placed obliquely across the esophagus; however, because of the bend of the esophagus to the left at the upper edge of the hiatus, the two were placed at right angle to each other, which resulted in a horizontal pressure profile of the CD on the LES. Our observations suggest a unique shape of the LES, CD, and the anatomical relationship between the two, which provides a possible explanation as to why the LES pressure shows circumferential and axial asymmetry. Our findings have implication for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in achalasia esophagus. NEW & NOTEWORTHY We used computed tomography scan imaging with three-dimensional esophago-gastric junction (EGJ) pressure recordings to determine functional morphology of the lower esophageal sphincter (LES) and crural diaphragm and its relationship to EGJ anatomy. The LES pressure profile was unique with the LES length longer and pressures lower toward the lesser curvature of the stomach, as compared with the greater curvature. Our findings have implications for the length and circumferential orientation of myotomy incision required for the ablation of LES pressure in the achalasia esophagus. Copyright © 2017 the American Physiological Society.
Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants.
Larregina, A T; Morelli, A E; Kolkowski, E; Sanjuan, N; Barboza, M E; Fainboim, L
1997-01-01
Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma). Images Figure 1 PMID:9227332
Safroneeva, E; Vavricka, S R; Fournier, N; Pittet, V; Peyrin-Biroulet, L; Straumann, A; Rogler, G; Schoepfer, A M
2015-10-01
The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication. © 2015 John Wiley & Sons Ltd.
Prabdial-Sing, N; Blackard, J T; Puren, A J; Mahomed, A; Abuelhassan, W; Mahlangu, J; Vermeulen, M; Bowyer, S M
2016-03-01
Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ∼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.
Scalia, Santo; Casolari, Alberto; Iaconinoto, Antonietta; Simeoni, Silvia
2002-11-07
The effects of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the base-catalyzed degradation and light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC) were investigated. Reversed-phase liquid chromatography was used to study the interaction between natural and modified cyclodextrins, added to the mobile phase, and the sunscreen. Among the available cyclodextrins (beta-CD, HP-beta-CD, hydroxypropyl-alpha-cyclodextrin and hydroxypropyl-gamma-cyclodextrin), only HP-beta-CD and beta-CD produced a significant decrease in the chromatographic retention of trans-EHMC. The complexation of the sunscreen agent with HP-beta-CD and beta-CD was confirmed by thermal analysis and nuclear magnetic resonance spectroscopy. beta-CD depressed the decomposition of trans-EHMC in alkaline solutions more effectively than HP-beta-CD. Moreover, the irradiation-induced degradation of the sunscreen agent in emulsion vehicles was reduced by complexation with beta-CD (the extent of degradation was 26.1% for the complex compared to 35.8% for free trans-EHMC) whereas HP-beta-CD had no significant effect. Therefore, the complex of beta-CD with trans-EHMC enhances the chemical- and photo-stability of the sunscreen agent. Moreover, it limits adverse interactions of the UV filter with other formulation ingredients.
Microheterogeneity in CH3OH/CD3OH mixture
NASA Astrophysics Data System (ADS)
Wrzeszcz, Władysław; Mazurek, Sylwester; Szostak, Roman; Tomza, Paweł; Czarnecki, Mirosław A.
2018-01-01
Recently, we demonstrated the presence of microheterogeneity in binary mixtures of unlike alcohols. [RSC Adv. 2016, 6, 37195-37202] The aim of this work was examination if this phenomenon occurs also in the mixture of very similar alcohols like CH3OH and CD3OH. Theoretical calculations suggest that the isotopic substitution in methyl group influences properties of the OH group. Hence, one can expect that this effect may lead to partial separation of CH3OH and CD3OH at a molecular level and it contributes to deviation from the ideal mixture. This work evidences that CH3OH/CD3OH mixture also deviates from the ideal one, but the extent of this deviation is much smaller as compared with the mixtures of other alcohols. It is of particular note that this deviation results mainly from the difference between the CH3 and CD3 groups, while the contribution from the OH groups is small. The structure of CH3OH/CD3OH mixture at a molecular level is similar to the structure of binary mixtures of other alcohols. The mixture is composed of the homoclusters of both alcohols and the mixed clusters. The homoclusters existing in the mixture are similar to those present in bulk alcohols. The highest population of the heteroclusters and the largest deviation from the ideal mixture were observed at equimolar mixture. Both the experimental and theoretical results reveal that in CH3OH/CD3OH mixture dominate the cyclic tetramers and larger clusters, while the population of the linear clusters is negligible. Though the extent and strength of hydrogen bonding in both alcohols are the same, the position and intensity of the 2ν(OH) band for CH3OH and CD3OH are different. We propose possible explanation of this observation.
Microheterogeneity in CH3OH/CD3OH mixture.
Wrzeszcz, Władysław; Mazurek, Sylwester; Szostak, Roman; Tomza, Paweł; Czarnecki, Mirosław A
2018-01-05
Recently, we demonstrated the presence of microheterogeneity in binary mixtures of unlike alcohols. [RSC Adv. 2016, 6, 37195-37202] The aim of this work was examination if this phenomenon occurs also in the mixture of very similar alcohols like CH 3 OH and CD 3 OH. Theoretical calculations suggest that the isotopic substitution in methyl group influences properties of the OH group. Hence, one can expect that this effect may lead to partial separation of CH 3 OH and CD 3 OH at a molecular level and it contributes to deviation from the ideal mixture. This work evidences that CH 3 OH/CD 3 OH mixture also deviates from the ideal one, but the extent of this deviation is much smaller as compared with the mixtures of other alcohols. It is of particular note that this deviation results mainly from the difference between the CH 3 and CD 3 groups, while the contribution from the OH groups is small. The structure of CH 3 OH/CD 3 OH mixture at a molecular level is similar to the structure of binary mixtures of other alcohols. The mixture is composed of the homoclusters of both alcohols and the mixed clusters. The homoclusters existing in the mixture are similar to those present in bulk alcohols. The highest population of the heteroclusters and the largest deviation from the ideal mixture were observed at equimolar mixture. Both the experimental and theoretical results reveal that in CH 3 OH/CD 3 OH mixture dominate the cyclic tetramers and larger clusters, while the population of the linear clusters is negligible. Though the extent and strength of hydrogen bonding in both alcohols are the same, the position and intensity of the 2ν(OH) band for CH 3 OH and CD 3 OH are different. We propose possible explanation of this observation. Copyright © 2017 Elsevier B.V. All rights reserved.
2016-01-01
For 2015, the U.S. Energy Information Administration (EIA) estimates that members of the Organization of the Petroleum Exporting Countries (OPEC) earned about $404 billion in net oil export revenues (unadjusted for inflation). This represents a 46% decline from the $753 billion earned in 2014, mainly as a result of a precipitous fall in average annual crude oil prices during the year, and to a lesser extent to decreases in the level of OPEC net oil exports. The 2015 revenue total was the lowest earnings for OPEC since 2004.
Variability of plasma-line enhancement in ionospheric modification experiments.
NASA Technical Reports Server (NTRS)
Fejer, J. A.
1972-01-01
A simple explanation for the variations of plasma-line intensity is suggested. The explanation is based on the fact that the plasma waves responsible for scattering the radar waves occur over a very limited range of heights. The explanation further makes use of the fact that the position of these height ranges of generation depends primarily on the gradient of the number density and to a lesser extent on the temperature and the orientation of the diagnostic radar beam.
Ozuna, G.B.; Small, T.A.
1993-01-01
Major pathways of potential contaminant migration off the bases include the local streams of Medio and Leon Creeks, and to a lesser extent, the shallow ground water beneath the bases. Although the Uvalde Gravel is not a source of shallow ground water at Medina Base, it drains water quickly, and wastes that might be buried in the gravel could be a potential source of contamination during brief ground-water recharge periods resulting from major precipitation.
2002-09-01
employed by the supermarket industry in 1973. Other common linear bar code symbologies are Code 39, pioneered by the defense and automotive industries...Teller Machine ( ATM ) cards are one of the prominent uses of this technology, but to a lesser extent, the technology has been used for shop floor...additional power is transmitted to it through the probe, extending its charge. There is a risk of data loss if the CMB is not accessed from time to time
Implications for the UK of solar-power satellites /s.p.s/ as an energy source
NASA Technical Reports Server (NTRS)
Shelton, R. M.
1980-01-01
The solar power satellite concept which would make the sun's radiation available on earth as a source of energy, is discussed. Attention is given to the concept currently under evaluation in the USA, and also in Europe, though to a lesser extent. The advantages and problems associated with its adoption by the UK as a major source of electrical energy are discussed. The discussion covers topics such as sizing, reference system, and construction, costs, and problem areas.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bertok, L.; Nagy, S.U.
Experiments were performed to demonstrate that, while the shock-inducing dose of parent (toxic) endotoxin significantly decreases the serum T4 level of rats and inhibits the T4 response given to exogenous thyroid stimulating hormone (TSH), the radio-detoxified (/sup 60/Co-gamma, 150 kGy) endotoxin preparation does not inhibit the response to exogenous TSH. It also decreases serum T4 level to a lesser extent than untreated endotoxin.
Report on the OJT Study Task. On-the-Job Training in the Department of Defense
1981-01-01
it is not presently possible to compare these costs with OJT costs for use as a factor in determining the best allocation of learning tasks between...further development by the Services and support, at least in principle, by OSD. Each Service, to a greater or lesser extent, has something to learn from...ISD entails selection of tasks required for each skill and identifies those that are best taught in school and those that can be deferred to be learned
Wei, Ting; Lv, Xin; Jia, HongLei; Hua, Li; Xu, HuiHui; Zhou, Ran; Zhao, Jin; Ren, XinHao; Guo, JunKang
2018-05-15
In this study, we investigated the ameliorative effects of salicylic acid (SA), metal ion (Fe(II)), and plant growth-promoting bacteria Burkholderia sp. D54 (B) on two tomato genotypes with different Cd tolerances under Cd stress, viz. Liger (Cd tolerant) and Tabd (Cd sensitive). The plant biomass, Cd accumulation, antioxidative response, pigment content and photosynthetic performance were determined. According to the results, exogenous application of SA, Fe(II) and Burkholderia sp. D54 or their complex effectively reduced Cd accumulation and increased biomass of root, stem and leaves in both Cd sensitive and Cd tolerant genotypes. Among all treatments, SA+Fe+B exerted the best performance. Burkholderia sp. D54 effectively alleviated Cd-induced oxidative toxicity in both tomato genotypes, while SA ameliorated oxidative stress in Cd sensitive genotype. Photosynthetic pigment content and photosynthetic rate of Cd tolerant genotype was increased by all treatments, but only SA and Burkholderia sp. D54 treatment increased pigment contents and photosynthetic performance in Cd sensitive genotypes. All treatments significantly decreased Cd accumulation in both tomato genotypes. The effect of Cd reduction was Fe+SA+B>SA>Fe>B. Taken together, our results indicated that exogenous application of SA, Fe(II) and Burkholderia sp. D54 could alleviate the Cd toxicity in both Cd sensitive and Cd tolerant genotypes, although the extent varies. Copyright © 2018 Elsevier Ltd. All rights reserved.
The October 17, 1989, Loma Prieta, California, earthquake: selected photographs
Nakata, John K.; Meyer, C.E.; Wilshire, H.G.; Tinsley, J. C.; Updegrove, W.S.; Peterson, D.M.; Ellen, S.D.; Haugerud, R.A.; McLaughlin, R.J.; Fisher, G.R.; Diggles, M.F.
1999-01-01
This CD-ROM contains 103 digitized color 35-mm images from Open-File Report 90-547 (Nakata and others, 1990). Our photographic coverage reflects the time and resources available immediately after the event and is not intended to portray the full extent of earthquake damage. This CD-ROM provides images for use by the interested public, multimedia producers, desktop publishers, and the high-end printing industry.
Use of Maize (Zea mays L.) for phytomanagement of Cd-contaminated soils: a critical review.
Rizwan, Muhammad; Ali, Shafaqat; Qayyum, Muhammad Farooq; Ok, Yong Sik; Zia-Ur-Rehman, Muhammad; Abbas, Zaheer; Hannan, Fakhir
2017-04-01
Maize (Zea mays L.) has been widely adopted for phytomanagement of cadmium (Cd)-contaminated soils due to its high biomass production and Cd accumulation capacity. This paper reviewed the toxic effects of Cd and its management by maize plants. Maize could tolerate a certain level of Cd in soil while higher Cd stress can decrease seed germination, mineral nutrition, photosynthesis and growth/yields. Toxicity response of maize to Cd varies with cultivar/varieties, growth medium and stress duration/extent. Exogenous application of organic and inorganic amendments has been used for enhancing Cd tolerance of maize. The selection of Cd-tolerant maize cultivar, crop rotation, soil type, and exogenous application of microbes is a representative agronomic practice to enhance Cd tolerance in maize. Proper selection of cultivar and agronomic practices combined with amendments might be successful for the remediation of Cd-contaminated soils with maize. However, there might be the risk of food chain contamination by maize grains obtained from the Cd-contaminated soils. Thus, maize cultivation could be an option for the management of low- and medium-grade Cd-contaminated soils if grain yield is required. On the other hand, maize can be grown on Cd-polluted soils only if biomass is required for energy production purposes. Long-term field trials are required, including risks and benefit analysis for various management strategies aiming Cd phytomanagement with maize.
Aytac, Zeynep; Yildiz, Zehra Irem; Kayaci-Senirmak, Fatma; Tekinay, Turgay; Uyar, Tamer
2017-09-15
The volatility and limited water solubility of linalool is a critical issue to be solved. Here, we demonstrated the electrospinning of polymer-free nanofibrous webs of cyclodextrin/linalool-inclusion complex (CD/linalool-IC-NFs). Three types of modified cyclodextrin (HPβCD, MβCD, and HPγCD) were used to electrospin CD/linalool-IC-NFs. Free-standing CD/linalool-IC-NFs facilitate maximum loading of linalool up to 12% (w/w). A significant amount of linalool (45-89%) was preserved in CD/linalool-IC-NFs, due to enhancement in the thermal stability of linalool by cyclodextrin inclusion complexation. Remarkably, CD/linalool-IC-NFs have shown fast-dissolving characteristics in which these nanofibrous webs dissolved in water within two seconds. Furthermore, linalool release from CD/linalool-IC-NFs inhibited growth of model Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria to a great extent. Briefly, characteristics of liquid linalool have been preserved in a solid nanofiber form and designed CD/linalool-IC-NFs confer high loading capacity, enhanced shelf life and strong antibacterial activity of linalool. Copyright © 2017 Elsevier Ltd. All rights reserved.
Child Maltreatment and Children's Developmental Trajectories in Early- to Middle-Childhood
Font, Sarah A.; Berger, Lawrence M.
2014-01-01
Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Well-Being study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes. PMID:25521556
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bache, C.A.; Lisk, D.J.; Shane, B.S.
The effectiveness of filter tips for reducing cadmium, tar, nicotine, carbon monoxide and carbon dioxide in cigarettes was studied. The cigarettes were made from tobacco grown on municipal sewage sludge-amended soil and were therefore high in cadmium. When machine-smoked, filter tips did not result in a significant reduction of cadmium deposited on Cambridge filters. This may indicate that a considerable fraction of cadmium is present in the vapor phase of the smoke and therefore not reduced to the same extent as the tar by certain filters. Nicotine and carbon monoxide were reduced to a lesser extent than tar. This indicatesmore » that the filter tip has influenced the combustion of the tobacco column during smoking.« less
Sarkar, Anupam; Bhagat, Jacky; Ingole, Baban S; Rao, Durga P; Markad, Vijaykumar L
2015-02-01
This paper presents an evaluation of the genotoxic effects of cadmium chloride (CdCl2 ) on marine gastropod, Nerita chamaeleon following the technique of comet assay and the DNA alkaline unwinding assay (DAUA). In this study, the extent of DNA damage in gill cells of N. chamaeleon was measured after in vivo exposure to four different concentrations (10, 25, 50, and 75 µg/L) of CdCl2 . In vitro exposure of hydrogen peroxide (H2 O2 ; 1, 10, 25, and 50 µM) of the gill cells showed a significant increase in the percentage tail DNA, Olive tail moment, and tail length (TL). Significant changes in percentage tail DNA by CdCl2 exposure were observed in all exposed groups of snails with respect to those in control. Exposure to 75 µg/L of CdCl2 produced significant decrease in DNA integrity as measured by DAUA at all duration with respect to control. In vivo exposure to different concentrations of CdCl2 (10, 25, 50, and 75 µg/L) to N. chamaeleon showed considerable increase in DNA damage as observed by both alkaline comet assay and the DAUA. The extent of DNA damage in marine gastropods determined by the application of alkaline comet assay and DAUA clearly indicated the genotoxic responses of marine gastropod, N. chamaeleon to a wide range of cadmium concentration in the marine environment. © 2013 Wiley Periodicals, Inc.
Relating FTS Catalyst Properties to Performance
NASA Technical Reports Server (NTRS)
Ma, Wenping; Ramana Rao Pendyala, Venkat; Gao, Pei; Jermwongratanachai, Thani; Jacobs, Gary; Davis, Burton H.
2016-01-01
During the reporting period June 23, 2011 to August 31, 2013, CAER researchers carried out research in two areas of fundamental importance to the topic of cobalt-based Fischer-Tropsch Synthesis (FTS): promoters and stability. The first area was research into possible substitute promoters that might be used to replace the expensive promoters (e.g., Pt, Re, and Ru) that are commonly used. To that end, three separate investigations were carried out. Due to the strong support interaction of ?-Al2O3 with cobalt, metal promoters are commonly added to commercial FTS catalysts to facilitate the reduction of cobalt oxides and thereby boost active surface cobalt metal sites. To date, the metal promoters examined have been those up to and including Group 11. Because two Group 11 promoters (i.e., Ag and Au) were identified to exhibit positive impacts on conversion, selectivity, or both, research was undertaken to explore metals in Groups 12 - 14. The three metals selected for this purpose were Cd, In, and Sn. At a higher loading of 25%Co on alumina, 1% addition of Cd, In, or Sn was found to-on average-facilitate reduction by promoting a heterogeneous distribution of cobalt consisting of larger lesser interacting cobalt clusters and smaller strongly interacting cobalt species. The lesser interacting species were identified in TPR profiles, where a sharp low temperature peak occurred for the reduction of larger, weakly interacting, CoO species. In XANES, the Cd, In, and Sn promoters were found to exist as oxides, whereas typical promoters (e.g., Re, Ru, Pt) were previously determined to exist in an metallic state in atomic coordination with cobalt. The larger cobalt clusters significantly decreased the active site density relative to the unpromoted 25%Co/Al2O3 catalyst. Decreasing the cobalt loading to 15%Co eliminated the large non-interacting species. The TPR peak for reduction of strongly interacting CoO in the Cd promoted catalyst occurred at a measurably lower temperature than in the unpromoted catalyst. Nevertheless, the Co clusters remained slightly larger, on average, in comparison with the unpromoted 15%Co/Al2O3 reference catalyst. None of the promoted catalysts (i.e., with Cd, In, or Sn) exhibited surface Co0 site densities higher than that of the unpromoted catalyst. In activity testing, the activities were even much lower than what was expected from the H2-TPD results. Two possible explanations were proposed: (1) the promoters may be located on the surfaces of cobalt particles, blocking surface Co0 but being able to desorb hydrogen or (2) the promoters may facilitate Co oxidation during FTS, as previously observed by Huffman and coworkers when K was added to cobalt catalysts.
Dai, Zi-yun; Shu, Wen-sheng; Liao, Bin; Wan, Cai-yun; Li, Jin-tian
2011-06-01
Averrhoa carambola L., a high-biomass tropical tree, has recently been shown to be a strong accumulator of cadmium (Cd) and has great potential for Cd phytoextraction. In the present study, field studies and a controlled-environment experiment were combined to establish the extent of variation in Cd tolerance and accumulation at the cultivar level using 14 to 19 cultivars of A. carambola. The results indicated that all cultivars tested could accumulate Cd at high but different levels, and that Cd tolerance also varied greatly between these cultivars. It is confirmed that the high Cd tolerance and accumulation capacity are species-level and constitutional traits in A. carambola. However, no correlation was detected between tolerance index and accumulation of Cd in different cultivars, suggesting that the two traits are independent in this woody Cd accumulator. More importantly, cultivar Wuchuan Sweet (WCT) was shown to have the highest Cd-extraction potential; it yielded a high shoot biomass of 30 t ha(-1) in 230 d, and extracted 330 g ha(-1) Cd in the aerial tissues grown in Cd-contaminated field soil, which accounted for 12.8% of the total soil Cd in the top 20 cm of the soil profile.
Nieva-Echevarría, Bárbara; Goicoechea, Encarnación; Guillén, María D
2017-11-15
The effect of the presence of ovalbumin and soy protein isolate on lipolysis and oxidation taking place during in vitro gastrointestinal digestion of slightly oxidized sunflower and flaxseed oils was addressed. The extent of lipolysis, the molar proportions of acyl groups/fatty acids after digestion, and the oxidation products formed were studied by Proton Nuclear Magnetic Resonance. The presence of proteins provoked a higher hydrolysis in triglycerides, a lower decrease of polyunsaturated chains, and a lower generation of oxidation compounds (conjugated dienes in chains having also hydroperoxy/hydroxy groups, epoxides and aldehydes); the formation of hydroxides was clearly favoured over that of hydroperoxides. Study of headspace composition by Solid Phase Microextraction-Gas Chromatography/Mass Spectrometry confirmed that oxidation advanced to a lesser extent in the presence of protein. Thus, amino acids/peptides released during digestion may show antioxidant properties, affecting not only the extent of lipid oxidation, but also reactions pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.
Söderlund, Therese; Madison, Guy
2017-01-01
Gender studies (GS) has been challenged on epistemological grounds. Here, we compare samples of peer-reviewed academic journal publications written by GS authors and authors from closely related disciplines in the social sciences. The material consisted of 2805 statements from 36 peer-reviewed journal articles, sampled from the Swedish Gender Studies List, which covers >12,000 publications. Each statement was coded as expressing a lack of any of three aspects of objectivity: Bias, Normativity, or Political activism, or as considering any of four realms of explanation for the behaviours or phenomena under study: Biology/genetics, Individual/group differences, Environment/culture, or Societal institutions. Statements in GS publications did to a greater extent express bias and normativity, but not political activism. They did also to a greater extent consider cultural, environmental, social, and societal realms of explanation, and to a lesser extent biological and individual differences explanations.
Ménard, Lucie; Turgeon, Christine; Trudeau-Fisette, Paméla; Bellavance-Courtemanche, Marie
2016-01-01
The impact of congenital visual deprivation on speech production in adults was examined in an ultrasound study of compensation strategies for lip-tube perturbation. Acoustic and articulatory analyses of the rounded vowel /u/ produced by 12 congenitally blind adult French speakers and 11 sighted adult French speakers were conducted under two conditions: normal and perturbed (with a 25-mm diameter tube inserted between the lips). Vowels were produced with auditory feedback and without auditory feedback (masked noise) to evaluate the extent to which both groups relied on this type of feedback to control speech movements. The acoustic analyses revealed that all participants mainly altered F2 and F0 and, to a lesser extent, F1 in the perturbed condition - only when auditory feedback was available. There were group differences in the articulatory strategies recruited to compensate; while all speakers moved their tongues more backward in the perturbed condition, blind speakers modified tongue-shape parameters to a greater extent than sighted speakers.
Diez, M C; Gallardo, F; Tortella, G; Rubilar, O; Navia, R; Bornhardt, C
2012-03-01
The white-rot fungus Anthracophyllum discolor immobilized on wheat grains was evaluated for chlorophenol (2,4-dichlorophenol, 2,4,6-trichlorophenol and pentachlorophenol) degradation in allophanic soil columns activated by acidification. Columns without inoculation were used as the control to evaluate the adsorption capacity of the soil columns. The chlorophenols were removed efficiently in soil columns by both adsorption and degradation processes. In inoculated soil columns, 2,4-dichlorophenol was highly degraded and this degradation is associated with a high production of manganese peroxidase. 2,4,6-trichlorophenol was degraded to a lesser extent compared with 2,4-dichlorophenol. Pentachlorophenol was first removed by adsorption and then through degradation by the fungus. Manganese peroxidase activity was lowest when the column was fed with pentachlorophenol and highest when the column was fed with 2,4-dichlorophenol. Laccase was also produced by the fungus but to a lesser degree. Copyright © 2010 Elsevier Ltd. All rights reserved.
Breaking the Pressure Barrier: A History of the Spacesuit Injection Patch
NASA Technical Reports Server (NTRS)
McFarland, Shane M.; Weaver, Aaron S.
2013-01-01
The spacesuit assembly has a fascinating and complicated history dating back to the early 1930s. Much has been written on this history from an assembly perspective and, to a lesser extent, a component perspective. However, little has been written or preserved specifically on smaller, lesser-known aspects of pressure suit design. One example of this is the injection patch - a small 2-in.-diameter disk on the leg of the Apollo suit that facilitated a medical injection when pressurized, and the only known implementation of such a feature on a flight suit. Whereas many people are aware this feature existed, very little is known of its origin, design, and use, and the fact that the Apollo flight suit was not the only instance in which such a feature was implemented. This paper serves to tell the story of this seeming "afterthought" of a feature, as well as the design considerations heeded during the initial development of subsequent suits.
Zeng, Huawei; Briske-Anderson, Mary; Wu, Min; Moyer, Mary P
2012-01-01
Methylselenol is hypothesized to be a critical selenium metabolite for anticancer action, and differential chemopreventive effects of methylselenol on cancerous and noncancerous cells may play an important role. In this study, the submicromolar concentrations of methylselenol were generated by incubating methionase with seleno-L methionine, and colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. Similarly, the examination of mitogen-activated protein kinase (MAPK) and cellular myelocytomatosis oncogene (c-Myc) signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 and p38 mitogen-activated protein kinase and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other finding is that methylselenol inhibits sarcoma kinase phosphorylation in HCT116 cells. In contrast, methylselenol upregulated the phosphorylation of sarcoma and focal adhesion kinase survival signals in the noncancerous NCM460 cells. Collectively, methylselenol's stronger potential of inhibiting cell proliferation/survival signals in the cancerous HCT116 cells when compared with that in noncancerous NCM460 cells may partly explain the potential of methylselenol's anticancer action.
Wirth, Markus; Schramm, Juliane; Bautz, Maximilian; Hofauer, Benedikt; Edenharter, Günther; Ott, Armin; Heiser, Clemens
2018-01-01
In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.
Schultz-Nielsen, Marie Louise; Tekin, Erdal; Greve, Jane
2016-05-01
This paper examines whether nutritional disruptions experienced during the stage of fetal development impair an individual's labor market productivity later in life. We consider intrauterine exposure to the month of Ramadan as a natural experiment that might cause shocks to the inflow of nutrients essential for fetal development. Specifically, we use administrative data from Denmark to investigate the impact of exposure to Ramadan in utero on labor market outcomes of adult Muslim males, including employment status, annual salary, hourly wage rate, and hours of work. Our findings indicate that potential exposure to nutritional disruptions during a critical stage of fetal development is likely to have scarring effects on the fetus expressed as poor labor market outcomes later in life. Specifically, exposure to Ramadan around the 7th month of gestation results in a lower likelihood of employment and, to a lesser extent, a lower salary, and reduced labor supply. For example, the 7th month intrauterine exposure to Ramadan is associated with a 2.6 percentage points reduction in the likelihood of employment among Muslim males. We do not find an impact on the wage rate. Finally, we also document suggestive evidence that these results may partially be driven by increased disability and to a lesser extent by poor educational attainment among those who were exposed to Ramadan during this particular period in utero. Copyright © 2016 Elsevier B.V. All rights reserved.
Kauw, Dirkjan; Repping-Wuts, Han; Noordzij, Alida; Stikkelbroeck, Nike; Hermus, Ad; Faber, Marjan
2015-02-25
Addison's disease and Cushing's syndrome are rare. The Dutch Adrenal Society offers an online forum for Dutch adrenal patients to meet and communicate. However, little is known about the added value such a forum has for the delivery of patient-centered care. Our aim was to analyze the purposes of online patient-to-patient forum conversations, within the context of patient-centered care. For this study a consecutive sample of 300 questions ("threads") from the past 3.5 years was selected from the forum. The content of these patient-driven questions was analyzed based on the dimensions of patient-centeredness of the Picker Institute. This analysis was performed using ATLAS.ti. From the 390 questions analyzed, 80.8% (N=315) were intended to gain more information about the disease, the treatment, and to verify if other patients had similar complaints. To a much lesser extent (38/390, 9.7%), questions expressed a call for emotional support. Patients answered primarily by giving practical tips to fellow patients and to share their own experiences. On an online patient forum for Cushing's syndrome and Addison's disease, patients appear to primarily gain knowledge and, to a lesser extent, emotional support from their peers. This experience-based knowledge has become a very important information source. As such, patients can make a substantial contribution to the creation of patient-centered care if this knowledge is integrated into the care provided by health care professionals.
Changes in the Areal Extent of Arctic Sea Ice: Observations from Satellites
NASA Technical Reports Server (NTRS)
Parkinson, Claire L.
2000-01-01
Wintertime sea ice covers 15 million square kilometers of the north polar region, an area exceeding one and a half times the area of the U. S. Even at the end of the summer melt season, sea ice still covers 7 million square kilometers. This vast ice cover is an integral component of the climate system, being moved around by winds and waves, restricting heat and other exchanges between the ocean and atmosphere, reflecting most of the solar radiation incident on it, transporting cold, relatively fresh water equatorward, and affecting the overturning of ocean waters underneath, with impacts that can be felt worldwide. Sea ice also is a major factor in the Arctic ecosystem, affecting life forms ranging from minute organisms living within the ice, sometimes to the tune of millions in a single ice floe, to large marine mammals like walruses that rely on sea ice as a platform for resting, foraging, social interaction, and breeding. Since 1978, satellite technology has allowed the monitoring of the vast Arctic sea ice cover on a routine basis. The satellite observations reveal that, overall, the areal extent of Arctic sea ice has been decreasing since 1978, at an average rate of 2.7% per decade through the end of 1998. Through 1998, the greatest rates of decrease occurred in the Seas of Okhotsk and Japan and the Kara and Barents Seas, with most other regions of the Arctic also experiencing ice extent decreases. The two regions experiencing ice extent increases over this time period were the Bering Sea and the Gulf of St. Lawrence. Furthermore, the satellite data reveal that the sea ice season shortened by over 25 days per decade in the central Sea of Okhotsk and the eastern Barents Sea, and by lesser amounts throughout much of the rest of the Arctic seasonal sea ice region, although not in the Bering Sea or the Gulf of St. Lawrence. Concern has been raised that if the trends toward shortened sea ice seasons and lesser sea ice coverage continue, this could entail major consequences to the polar climate and to the lifestyles (and perhaps even the survivability) of polar bears and other polar species.
Personal and lifestyle characteristics predictive of the consumption of fast foods in Australia.
Mohr, Philip; Wilson, Carlene; Dunn, Kirsten; Brindal, Emily; Wittert, Gary
2007-12-01
To identify key predictors of fast-food consumption from a range of demographic, attitudinal, personality and lifestyle variables. We analysed data from a nationwide survey (n = 20 527) conducted in Australia by Nielsen Media Research. Items assessing frequency of fast-food consumption at (1) eat in and (2) take away were regressed onto 12 demographic, seven media consumption, and 23 psychological and lifestyle variables, the latter derived from factor analysis of responses to 107 attitudinal and behavioural items. Stepwise multiple regression analyses explained 29.6% of the variance for frequency of take-away and 9.6% of the variance for frequency of eat-in consumption of fast foods. Predictors of more frequent consumption of fast food at take away (and, to a lesser extent, eat in) included lower age - especially under 45 years, relative indifference to health consequences of behaviour, greater household income, more exposure to advertising, greater receptiveness to advertising, lesser allocation of time for eating, and greater allocation of time to home entertainment. There were no effects for occupational status or education level. The effects for age suggest that fast-food take-away consumption is associated with a general cultural shift in eating practices; individual differences in attitudinal and lifestyle characteristics constitute additional, cumulative, predictive factors. The role of advertising and the reasons for the lesser explanatory value of the eat-in models are important targets for further research.
Cadmium isotope fractionation during adsorption to Mn-oxyhydroxide
NASA Astrophysics Data System (ADS)
Wasylenki, L. E.; Swihart, J. W.
2013-12-01
The heavy metal cadmium is of interest both as a toxic contaminant in groundwater and as a critical nutrient for some marine diatoms [1], yet little is known about the biogeochemistry of this element. Horner et al. [2] suggested that Cd stable isotopes could potentially enable reconstruction of biological use of Cd in the marine realm: since cultured diatoms fractionate Cd isotopes [3], and ferromanganese crusts appear to incorporate a faithful record of deepwater Cd isotopes [2], depth profiles in such crusts may yield information about the extent of Cd assimilation of isotopically light Cd by diatoms over time. Although no work has yet been published regarding the use of stable isotopes to track reactive transport of Cd in contaminated aquifers, others have recently demonstrated the potential of isotopes to track reactions affecting the mobility of other toxic metals (e.g., [4]). With both of these potential applications in mind, we conducted two sets of experiments, at low and high ionic strength, in which Cd partially adsorbed to potassium birnessite. Our goals are to quantify the fractionations and to constrain the mechanisms governing Cd isotope behavior during adsorption to an environmentally abundant scavenger of Cd. Suspensions of synthetic birnessite were doped with various amounts of dissolved Cd2+ at pH ~8.3. Following reaction, the dissolved and adsorbed pools of Cd were separated by filtration, purified by anion exchange chromatography, and analyzed by multicollector ICP-MS using a double-spike routine. In all cases, lighter isotopes preferentially adsorbed to the birnessite particles. At low ionic strength (I<0.01m), we observed a small fractionation of 0.15‰×0.05 (Δ114/112) that was constant as a function of the fraction of Cd adsorbed. This indicates a small equilibrium isotope effect, likely driven by a subtle shift in coordination geometry for Cd during adsorption. In a groundwater system with continuous flow of dissolved Cd, this fractionation might manifest as an open system Rayleigh trend, with isotope signatures along the flow path reflecting the extent to which adsorption attenuates mobility of Cd. In simplified synthetic seawater (I=0.7m), the magnitude of fractionation decreases slightly with increasing proportion of Cd adsorbed, suggesting a kinetic or Rayleigh effect (irreversible sorption). A time series (1-192 hours) shows that the fractionation decreases from 0.3‰ to 0.2‰ over the course of 8 days. A longer experiment is underway to determine whether our study supports the observation of Horner et al. that Cd partitioned between deepwater and ferromanganese crusts is isotopically homogeneous [2]. The difference in Cd isotope behavior between low and high ionic strength conditions is likely due to different speciation of Cd in solution; chloro- complexes dominate Cd speciation in artificial seawater, while Cd2+ dominates at low ionic strength. [1] Price & Morel (1990) Nature 344, 658. [2] Horner et al (2010) G-cubed doi:10.1029/2009GC002987. [3] Lacan et al. (2006) Geochim. Cosmochim. Acta. 70, 5104. [4] Berna et al. (2010) Env. Sci. & Tech. 44, 1043.
Malo, Courtney S; Huggins, Matthew A; Goddery, Emma N; Tolcher, Heather M A; Renner, Danielle N; Jin, Fang; Hansen, Michael J; Pease, Larry R; Pavelko, Kevin D; Johnson, Aaron J
2018-02-12
The contribution of antigen-presenting cell (APC) types in generating CD8 + T cell responses in the central nervous system (CNS) is not fully defined, limiting the development of vaccines and understanding of immune-mediated neuropathology. Here, we generate a transgenic mouse that enables cell-specific deletion of the H-2Kb MHC class I molecule. By deleting H-2K b on dendritic cells and macrophages, we compare the effect of each APC in three distinct models of neuroinflammation: picornavirus infection, experimental cerebral malaria, and a syngeneic glioma. Dendritic cells and macrophages both activate CD8 + T cell responses in response to these CNS immunological challenges. However, the extent to which each of these APCs contributes to CD8 + T cell priming varies. These findings reveal distinct functions for dendritic cells and macrophages in generating CD8 + T cell responses to neurological disease.
[Survey and evaluation of heavy metal in the major vegetables in Shaanxi Province].
Nie, Xiaoling; Cheng, Guoxia; Wang, Minjuan; Wang, Caixia; Du, Kejun
2015-09-01
To evaluate the contamination condition of the Pb, Cd, Hg and As in ten kinds of vegetables in Shaanxi Province. The Pb and Cd contents were determined by inductively coupled plasma mass spectrometry, and the As contents were determined by hydride generation-atomic fluorescence spectrometry, and the Hg contents were determined by mercury vapourmeter. One factor contamination index was employed to evaluate the metal pollution situation of different types of vegetables. Moreover, the health risk after intake of those heavy metals through vegetables were described. In ten kinds of vegetables of Shaanxi Province, the Pb contents in cowpea reached the alertness level, while the contents of Cd, Hg and As were below the safety level. What' s more, the contents of the Pb, Cd, Hg and As were below the safety level in other nine vegetables, and the over standard rate of were Hg > Pb > Cd > As. The contamination extents of Pb, Cd, Hg and As in ten kinds of vegetables in Shaanxi Province were low.
Chiba, Sahoko; Tsuchiya, Kimitake; Akashi, Takumi; Ishizuka, Masahiro; Okamoto, Tsukasa; Furusawa, Haruhiko; Tateishi, Tomoya; Kishino, Mitsuhiro; Miyazaki, Yasunari; Tateishi, Ukihide; Takemura, Tamiko; Inase, Naohiko
2016-06-01
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Xia, Jingya; Veselenak, Ronald L.; Gorder, Summer R.; Bourne, Nigel; Milligan, Gregg N.
2014-01-01
Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation. PMID:25485971
Whitney, P.R.
1981-01-01
Manganese oxide coatings on gravels from 255 sites on tributary streams in the Genesee River Watershed were analyzed for Mn, Fe, Zn, Cd, Co, Ni, Pb, and Cu. The results were compared with data on bedrock geology, surficial geology and land use, using factor analysis and stepwise multiple regression. All metals except Pb show strong positive correlation with Mn. This association results from the well-known tendency of Mn oxide precipitates to adsorb and incorporate dissolved trace metals. Pb may be present in a separate phase on the gravel surfaces; alternatively Pb abundance may be so strongly influenced by environmental factors that the effect of varying abundance of the carrier phase becomes relatively unimportant. When the effects of varying Mn abundance are allowed for, Pb and to a lesser extent Zn and Cu abundances are seen to be related to commercial, industrial and residential land use. In addition to this pollution effect, all the trace metals, Cd and Ni most strongly, tend to be more abundant in oxide coatings from streams in the forested uplands in the southern part of the area. This probably reflects increased geochemical mobility of the metals in the more acid soils and groundwater of the southern region. A strong Zn anomaly is present in streams draining areas underlain by the Lockport Formation. Oxide coatings in these streams contain up to 5% Zn, originating from disseminated sphalerite in the Lockport and secondary Zn concentrations in the overlying muck soils. The same group of metals, plus calcium and loss on ignition, were determined in the silt and clay (minus 230 mesh) fraction of stream sediments from 129 of the same sites, using a hot nitric acid leach. The amounts of manganese in the sediments are low (average 1020 ppm) and manganese oxides are, at most, of relatively minor significance in the trace-metal geochemistry of these sediments. The bulk of the trace metals in sediment appears to be associated with iron oxides, clays and organic matter. ?? 1981.
Singha, Krishnadipti; Mondal, Aniruddha; Ghosh, Subhash Chandra; Panda, Asit Baran
2018-02-02
CdS sheet-rGO nanocomposite as a heterogeneous photocatalyst enables visible-light-induced photocatalytic reduction of aromatic, heteroaromatic, aliphatic and sulfonyl azides to the corresponding amines using hydrazine hydrate as a reductant. The reaction shows excellent conversion and chemoselectivity towards the formation of the amine without self-photoactivated azo compounds. In the adopted strategy, CdS not only accelerates the formation of nitrene through photoactivation of azide but also enhances the decomposition of azide to a certain extent, which entirely suppressed formation of the azo compound. The developed CdS sheet-rGO nanocomposite catalyst is very active, providing excellent results under irradiation with a 40 W simple household CFL lamp. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Differences in dissolved cadmium and zinc uptake among stream insects: Mechanistic explanations
Buchwalter, D.B.; Luoma, S.N.
2005-01-01
This study examined the extent to which dissolved Cd and Zn uptake rates vary in several aquatic insect taxa commonly used as indicators of ecological health. We further attempted to explain the mechanisms underlying observed differences. By comparing dissolved Cd and Zn uptake rates in several aquatic insect species, we demonstrated that species vary widely in these processes. Dissolved uptake rates were not related to gross morphological features such as body size or gill size-features that influence water permeability and therefore have ionoregulatory importance. However, finer morphological features, specifically, the relative numbers of ionoregulatory cells (chloride cells), appeared to be related to dissolved metal uptake rates. This observation was supported by Michaelis-Menten type kinetics experiments, which showed that dissolved Cd uptake rates were driven by the numbers of Cd transporters and not by the affinities of those transporters to Cd. Calcium concentrations in exposure media similarly affected Cd and Zn uptake rates in the caddisfly Hydropsyche californica. Dissolved Cd and Zn uptake rates strongly co-varied among species, suggesting that these metals are transported by similar mechanisms.
Liu, Jia Nv; Zhou, Qi Xing; Wang, Song; Sun, Ting
2009-02-01
The role of ornamental plants has drawn much attention as the urban pollution levels exacerbate. Althaea rosea Cav. had showed its strong tolerance and accumulation ability of Cd in our previous work, thus, the effects of ethylenediamine triacetic acid (EDTA), ethylenegluatarotriacetic acid (EGTA) and sodium dodecyl sulfate (SDS) on its Cd phytoremediation capacity were further investigated in this work. It reconfirmed that the species had strong tolerance and accumulation ability of Cd. Particularly, the species can be regarded as a potential Cd-hyperaccumulator through applying chemical agents. However, different chelators and surfactants had great differences in affecting hyperaccumulating characteristics of the species. EGTA and SDS could not only increase the dry biomass of the plants, but also promote Cd accumulation in shoots and roots. On the contrary, EDTA was toxic to the species by restraining the growth of plants, although it could promote Cd accumulation in shoots and roots of the plants to a certain extent. Thus, EGTA and SDS were effective in enhancing phytoremediation with Althaea rosea Cav. for Cd contaminated soils, while EDTA is ineffective in this regard.
Impact of tannery effluents on the aquatic environment of the Buriganga River in Dhaka, Bangladesh.
Asaduzzaman, Mohammad; Hasan, Imtiaj; Rajia, Sultana; Khan, Nazneen; Kabir, Kazi Ahmed
2016-06-01
This study presents an overview of the existence and effects of six heavy metals, chromium (Cr), lead (Pb), cadmium (Cd), mercury (Hg), manganese (Mn), and aluminum (Al), in tannery effluents released to the Buriganga River in Dhaka, Bangladesh. The pollutants were found in three different sources, such as effluents from tanneries, contaminated river water and three species of fish-climbing perch (Anabas testudineus), spotted snakehead (Channa punctata), and Black tilapia (Oreochromis mossambicus) caught from the river. Tannery effluents, water, and fish samples were collected from three different factories, five sample stations, and three different harvesting points, respectively. Effluents from all three factories contained significant amounts of heavy metals, especially Cr (374.19 ppm in average), whereas lesser amounts were found in the tissues of the three fish species studied. The trends in tissue elemental concentrations of fish were Cr > Pb > Al > Hg > Mn > Cd. In most cases (Cr, Cd, Mn, and Al), heavy metal concentrations were found to be greater in climbing perch than in Black tilapia and spotted snakehead. Although the river water contained high concentrations of harmful heavy metals, the fish species under study had concentrations well below the permissible Food and Agriculture Organization/World Health Organization levels for those metals and seemed to be safe for human consumption. © The Author(s) 2014.
Child maltreatment and children's developmental trajectories in early to middle childhood.
Font, Sarah A; Berger, Lawrence M
2015-01-01
Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.
Willander, Johan; Sikström, Sverker; Karlsson, Kristina
2015-01-01
Previous studies on autobiographical memory have focused on unimodal retrieval cues (i.e., cues pertaining to one modality). However, from an ecological perspective multimodal cues (i.e., cues pertaining to several modalities) are highly important to investigate. In the present study we investigated age distributions and experiential ratings of autobiographical memories retrieved with unimodal and multimodal cues. Sixty-two participants were randomized to one of four cue-conditions: visual, olfactory, auditory, or multimodal. The results showed that the peak of the distributions depends on the modality of the retrieval cue. The results indicated that multimodal retrieval seemed to be driven by visual and auditory information to a larger extent and to a lesser extent by olfactory information. Finally, no differences were observed in the number of retrieved memories or experiential ratings across the four cue-conditions.
Gomes, J A P; Dua, H S; Rizzo, L V; Nishi, M; Joseph, A; Donoso, L A
2004-01-01
Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. PMID:14736792
Lee, Woo-Yong; Sanz, Maria-Jesus; Wong, Connie H Y; Hardy, Pierre-Olivier; Salman-Dilgimen, Aydan; Moriarty, Tara J; Chaconas, George; Marques, Adriana; Krawetz, Roman; Mody, Christopher H; Kubes, Paul
2014-09-23
CXCR6-GFP(+) cells, which encompass 70% invariant natural killer T cells (iNKT cells), have been found primarily patrolling inside blood vessels in the liver. Although the iNKT cells fail to interact with live pathogens, they do respond to bacterial glycolipids presented by CD1d on liver macrophage that have caught the microbe. In contrast, in this study using dual laser multichannel spinning-disk intravital microscopy of joints, the CXCR6-GFP, which also made up 60-70% iNKT cells, were not found in the vasculature but rather closely apposed to and surrounding the outside of blood vessels, and to a lesser extent throughout the extravascular space. These iNKT cells also differed in behavior, responding rapidly and directly to joint-homing pathogens like Borrelia burgdorferi, which causes Lyme disease. These iNKT cells interacted with B. burgdorferi at the vessel wall and disrupted dissemination attempts by these microbes into joints. Successful penetrance of B. burgdorferi out of the vasculature and into the joint tissue was met by a lethal attack by extravascular iNKT cells through a granzyme-dependent pathway, an observation also made in vitro for iNKT cells from joint but not liver or spleen. These results suggest a novel, critical extravascular iNKT cell immune surveillance in joints that functions as a cytotoxic barrier and explains a large increase in pathogen burden of B. burgdorferi in the joint of iNKT cell-deficient mice, and perhaps the greater susceptibility of humans to this pathogen because of fewer iNKT cells in human joints.
Stoebner, Pierre E; Rahmoun, Massilva; Ferrand, Christophe; Meunier, Laurent; Yssel, Hans; Pène, Jérôme
2006-08-01
Solar ultraviolet (UV) radiation has hazardous effects on human health that are, in part, associated with its immunosuppressive effects via the induction of interleukin (IL)-10 production. Although IL-10 is produced by both T helper type 2 (Th2) cells and T-regulatory type 1 (Tr1) cells, the relative contribution of either subset in UV radiation-induced immunosuppression has not been established. Here, we show that T cells isolated from non-treated allergic contact dermatitis (ACD) reactions, 48 h following nickel challenge and propagated for 7-10 days in the presence of IL-2, were mainly CD4(+) and produced IL-10, but little interferon-gamma. A single sub-erythematous solar-simulated radiation (SSR) prior to antigen challenge exposure resulted in a clinical attenuation of the intensity of ACD reactions which was associated with a significant increase in both the magnitude of IL-10 production by skin-infiltrating T cells and the frequency of IL-10-producing Tr1 cells. Skin-infiltrating T cells in SSR-exposed, as well as non-exposed, ACD reactions showed a perturbed T-cell receptor (TCR)-Vbeta repertoire, without overexpression of a particular TCR-Vbeta gene product, indicating the presence of high frequencies of nickel non-specific T cells in ACD reactions. These results show that a single sub-erythematous SSR induces immunosuppression via the cutaneous infiltration of IL-10-producing Tr1, and to a lesser extent, Th2 cells.
Yovchev, Mladen I.; Xue, Yuhua; Shafritz, David A.; Locker, Joseph; Oertel, Michael
2013-01-01
Background & Aim Considerable progress has been made in developing anti-fibrotic agents and other strategies to treat liver fibrosis; however, significant long-term restoration of functional liver mass has not yet been achieved. Therefore, we investigated whether transplanted hepatic stem/progenitor cells can effectively repopulate the liver with advanced fibrosis/cirrhosis. Methods Stem/progenitor cells derived from fetal livers or mature hepatocytes from DPPIV+ F344 rats were transplanted into DPPIV− rats with thioacetamide (TAA)-induced fibrosis/cirrhosis; rats were sacrificed 1, 2, or 4 months later. Liver tissues were analyzed by histochemistry, hydroxyproline determination, RT-PCR, and immunohistochemistry. Results After chronic TAA administration, DPPIV− F344 rats exhibited progressive fibrosis, cirrhosis and severe hepatocyte damage. Besides stellate cell activation, increased numbers of stem/progenitor cells (Dlk-1+, AFP+, CD133+, Sox-9+, FoxJ1+) were observed. In conjunction with partial hepatectomy (PH), transplanted stem/progenitor cells engrafted, proliferated competitively compared to host hepatocytes, differentiated into hepatocytic and biliary epithelial cells, and generated new liver mass with extensive long-term liver repopulation (40.8 ± 10.3%). Remarkably, more than 20% liver repopulation was achieved in the absence of PH, associated with reduced fibrogenic activity (e.g., expression of α-SMA, PDGFRβ, desmin, vimentin, TIMP1) and fibrosis (reduced collagen). Furthermore, hepatocytes can also replace liver mass with advanced fibrosis/cirrhosis, but to a lesser extent than FLSPCs. Conclusions This study is a Proof of Principle demonstration that transplanted epithelial stem/progenitor cells can restore injured parenchyma in a liver environment with advanced fibrosis/cirrhosis and exhibit anti-fibrotic effects. PMID:23840008
Hernández, Ana Jesus; Alexis, Stervin; Pastor, Jesús
2007-05-25
Two of the National Parks of the only Biosphere Reserve in the Caribbean Islands, the Jaragua-Bahoruco-Enriquillo reserve, occur mostly within the Pedernales province (Dominican Republic). In these National Parks, Jaragua and Bahoruco, almost every tropical forest ecosystem is represented, as are the land uses most common to the Dominican Republic. Despite soil being a key natural resource that needs to be considered in any sustainable development programme, the literature contains very little information on the soils of this region. In this study, we analysed 41 topsoil samples representing the main forest types and land uses of the province. The factors examined were fertility (OM, N, P, K) and heavy metal contents (Cu, Cr, Pb, Cd, Ni, Zn). Mean OM, N and total and available metal levels were almost invariably higher in the natural forest soils compared to those given over to human activities, especially cultivated soils. This difference suggests the uptake of metals by the crops and, to a lesser extent, by animals feeding on crop remains and grassland plants. This hypothesis is supported by high total and available metal contents, especially of Zn, Cu, Pb and, in smaller measure, of Cr recorded in the solid waste landfill of the city of Pedernales. It appears that the cutting down and burning practices of a nomad type of cultivation, as well as the pressures of intensive agriculture and livestock rearing have resulted in heavy metals bound to the soil's OM. We propose this is an important point to consider for the management of these lands.
Larchevêque, Marie; Ballini, Christine; Korboulewsky, Nathalie; Montès, Nicolas
2006-10-01
In Mediterranean frequently burnt areas, fire and erosion result in the decrease of soil fertility, so afforestation is a major concern. We carried out an in situ experiment of compost amendment to improve survival and growth of planted tree seedlings. One-year-tree seedlings of native species (Quercus ilex, Pinus halepensis and Pinus pinea) were planted on a frequently burnt calcareous site. Three rates of fresh co-composted sewage sludge and greenwastes (control without compost, 20 and 40 kg m(-2) of compost) were incorporated into the soil at each seedling stem. Changes of soil properties and tree development were studied during 3 years (2001-2003) and 2 years (2002-2003) respectively. The compost improved survival of Quercus ilex and Pinus pinea seedlings in severe drought conditions, but had no effect on Pinus halepensis. For all species seedling length and radial growth and NPK nutrition were increased for both rates of amendment. Amendment improved soil fertility, but available P concentration increased 13 fold in the neighbouring soil of seedlings amended at the maximal rate compared to control. However, amendment did not significantly increase concentrations of Cd, Cr, Ni and Pb in soils or tree seedlings. It increased Cu and Zn total and available concentrations in soils, while foliar Cu and Zn concentrations in the seedlings remained similar in all plots. Compost can efficiently help afforestation of dry soils with low organic matter content. However, sewage sludge concentrations in P, and to a lesser extent in Cu and Zn, limit rates of application that can be applied without environmental hazard.
Metal contamination in wildlife living near two zinc smelters
Beyer, W.N.; Pattee, O.H.; Sileo, L.; Hoffman, D.J.; Mulhern, B.M.
1985-01-01
Wildlife in an oak forest on Blue Mountain was studied 10 km upwind (Bake Oven Knob site) and 2 km downwind (Palmerton site) of two zinc smelters in eastern Pennsylvania, USA. Previous studies at sites near these smelters had shown changes in populations of soil microflora, lichens, green plants and litter-inhabiting arthropods. The 02 soil litter horizon at Palmerton was heavily contaminated with Pb (2700 mg kg-1), Zn (24000 mg kg-1), and Cd (710 mg kg-1), and to a lesser extent with Cu (440 mg kg-1). Various kinds of invertebrates (earthworms, slugs and millipedes) that feed on soil litter or soil organic matter were rare at, or absent from, the Palmerton site. Those collected at Bake Oven Knob tended to have much higher concentrations of metals than did other invertebrates. Frogs, toads and salamanders were very rare at, or absent from, the Palmerton site, but were present at Bake Oven Knob and at other sites on Blue Mountain farther from the smelters. Metal concentrations (dry wt) in different organisms from Palmerton were compared. Concentrations of Pb were highest in shrews (110 mg kg-1), followed by songbirds (56 mg kg-1), leaves (21 mg kg-1), mice (17 mg kg-1), carrion insects (14 mg kg-1), berries (4.0 mg kg-1), moths (4,3 mg kg-1) and fungi (3.7 mg kg-1). Concentrations of Cd, in contrast, were highest in carrion insects (25 mg kg-1 ),followed by fungi (9.8 mg kg-1), leaves (8.1 mg kg-1), shrews (7.3 mg kg-I), moths (4.9 mg kg-1), mice (2.6 mg kg -1), songbirds (2.5 mg kg -1) and berries (1.2 mg kg-1). Concentrations of Zn and Cu tended to be highest in the same organisms that had the highest concentrations of Cd. Only a small proportion of the metals in the soil became incorporated into plant foliage, and much of the metal contamination detected in the biota probably came from aerial deposition. The mice from both sites seemed to be healthy. Shrews had higher concentrations of metals than did mice, and one shrew showed evidence of Pb poisoning; its red blood cell ALAD activity was greatly reduced, one kidney contained acid-fast intranuclear inclusion bodies, and the other kidney had 280 mg kg-1 Pb (wet wt). The livers from two cuckoos from Palmerton had elevated Pb concentrations (18 and 25 mg kg-1, wet wt). Most of the songbirds seemed to be healthy.
Assessing cadmium exposure risks of vegetables with plant uptake factor and soil property.
Yang, Yang; Chang, Andrew C; Wang, Meie; Chen, Weiping; Peng, Chi
2018-07-01
Plant uptake factors (PUFs) are of great importance in human cadmium (Cd) exposure risk assessment while it has been often treated in a generic way. We collected 1077 pairs of vegetable-soil samples from production fields to characterize Cd PUFs and demonstrated their utility in assessing Cd exposure risks to consumers of locally grown vegetables. The Cd PUFs varied with plant species and pH and organic matter content of soils. Once normalized PUFs against soil parameters, the PUFs distributions were log-normal in nature. In this manner, the PUFs were represented by definable probability distributions instead of a deterministic figure. The Cd exposure risks were then assessed using the normalized PUF based on the Monte Carlo simulation algorithm. Factors affecting the extent of Cd exposures were isolated through sensitivity analyses. Normalized PUF would illustrate the outcomes for uncontaminated and slightly contaminated soils. Among the vegetables, lettuce was potentially hazardous for residents due to its high Cd accumulation but low Zn concentration. To protect 95% of the lettuce production from causing excessive Cd exposure risks, pH of soils needed to be 5.9 and above. Copyright © 2018 Elsevier Ltd. All rights reserved.
Excretion of cadmium and zinc during moulting in the grasshopper Omocestus viridulus (Orthoptera)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lindqvist, L.; Block, M.
1994-10-01
Nymphs of Omocestus viridulus (Orthoptera) were reared on grass leaves containing known amounts of [sup 109]Cd or [sup 65]Zn. After the animals molted to adults, contents of these metals were measured in the grasshoppers, in the cast of exuviae and in the feces produced during rearing. Dry weights of adult bodies and exuviae were lower for [sup 109]Cd-treated grasshoppers than for those given [sup 65]Zn. Exuviae accounted for only a minor part of the excreted [sup 109]Cd and [sup 65]Zn. The [sup 109]Cd was assimilated from food to a much smaller extent than was [sup 65]Zn. After 15 d ofmore » rearing, [approximately] 50% of the ingested [sup 65]Zn, but only 10% of the ingested [sup 109]Cd, remained in the grasshoppers. Because the amount of [sup 109]Cd in the grasshopper nymphs decreased with time, whereas that of the exuviae were constant, content in exuviae constituted a larger portion of the total content of [sup 109]Cd with increasing time between feeding of [sup 109]Cd and molting. For [sup 65]Zn there was no such trend.« less
Some empirical evidence for ecological dissonance theory.
Miller, D I; Verhoek-Miller, N; Giesen, J M; Wells-Parker, E
2000-04-01
Using Festinger's cognitive dissonance theory as a model, the extension to Barker's ecological theory, referred to as ecological dissonance theory, was developed. Designed to examine the motivational dynamics involved when environmental systems are in conflict with each other or with cognitive systems, ecological dissonance theory yielded five propositions which were tested in 10 studies. This summary of the studies suggests operationally defined measures of ecological dissonance may correlate with workers' satisfaction with their jobs, involvement with their jobs, alienation from their work, and to a lesser extent, workers' conflict resolution behavior and communication style.
Economic consequences for Medicaid of human immunodeficiency virus infection
Baily, Mary Ann; Bilheimer, Linda; Wooldridge, Judith; well, Kathryn Lang; Greenberg, Warren
1990-01-01
Medicaid is currently a major source of financing for health care for those with acquired immunodeficiency syndrome (AIDS) and to a lesser extent, for those with other manifestations of human immunodeficiency virus (HIV) infection. It is likely to become even more important in the future. This article focuses on the structure of Medicaid in the context of the HIV epidemic, covering epidemiological issues, eligibility, service coverage and use, and reimbursement. A simple methodology for estimating HI\\'-related Medicaid costs under alternative assumptions about the future is also explained. PMID:10113503
The Frictional Force with Respect to the Actual Contact Surface
NASA Technical Reports Server (NTRS)
Holm, Ragnar
1944-01-01
Hardy's statement that the frictional force is largely adhesion, and to a lesser extent, deformation energy is proved by a simple experiment. The actual contact surface of sliding contacts and hence the friction per unit of contact surface was determined in several cases. It was found for contacts in normal atmosphere to be about one-third t-one-half as high as the macroscopic tearing strength of the softest contact link, while contacts annealed in vacuum and then tested, disclosed frictional forces which are greater than the macroscopic strength.
Schilliger, Lionel; Tréhiou-Sechi, Emilie; Petit, Amandine M P; Misbach, Charlotte; Chetboul, Valérie
2010-12-01
Ultrasonography, and, to a lesser extent, echocardiography are now well-established, noninvasive, and painless diagnostic tools in herpetologic medicine. Various cardiac lesions have been previously described in reptiles, but valvulopathy is rarely documented in these animals and, consequently, is poorly understood. In this report, sinoatrial and atrioventricular insufficiencies were diagnosed in a 5-yr-old captive dyspneic Burmese python (Python molurus bivittatus) on the basis of echocardiographic and Doppler examination. This case report is the first to document Doppler assessment of valvular regurgitations in a reptile.
Food avoidance in athletes: FODMAP foods on the list.
Lis, Dana; Ahuja, Kiran D K; Stellingwerff, Trent; Kitic, Cecilia M; Fell, James
2016-09-01
We surveyed 910 athletes to assess behaviours towards self-selected food/ingredient avoidance to minimize gastrointestinal distress. Fifty-five percent eliminated at least 1 high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) food/category, with up to 82.6% reporting symptom improvement. In athletes indicating that high FODMAP foods trigger gastrointestinal symptoms, lactose (86.5%) was most frequently eliminated, followed by galactooligosaccharides (23.9%), fructose (23.0%), fructans (6.2%), and polyols (5.4%). Athletes avoid predominantly lactose and to a lesser extent other high FODMAP foods to reduce gastrointestinal distress.
Seasonal air and water mass redistribution effects on LAGEOS and Starlette
NASA Technical Reports Server (NTRS)
Gutierrez, Roberto; Wilson, Clark R.
1987-01-01
Zonal geopotential coefficients have been computed from average seasonal variations in global air and water mass distribution. These coefficients are used to predict the seasonal variations of LAGEOS' and Starlette's orbital node, the node residual, and the seasonal variation in the 3rd degree zonal coefficient for Starlette. A comparison of these predictions with the observed values indicates that air pressure and, to a lesser extent, water storage may be responsible for a large portion of the currently unmodeled variation in the earth's gravity field.
Human cortical activity related to unilateral movements. A high resolution EEG study.
Urbano, A; Babiloni, C; Onorati, P; Babiloni, F
1996-12-20
In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.
Trends in solid state electronics, part 2
NASA Technical Reports Server (NTRS)
Gassaway, J. D.
1972-01-01
Developments in the fields of semiconductors and magnetics are surveyed. Materials, devices, theory, and fabrication technology are discussed. Important events up until the present time are reported, and events are interpreted through historical perspective. A brief analysis of forces which have driven the development of today's electronic technology and some projections of present trends are given. More detailed discussions are presented for four areas of contemporary interest: amorphous semiconductors, bubble domain devices, charge-coupled devices, and electron and ion beam techniques. Beam addressed magnetic memories are reviewed to a lesser extent.
Recoilless fractions calculated with the nearest-neighbour interaction model by Kagan and Maslow
NASA Astrophysics Data System (ADS)
Kemerink, G. J.; Pleiter, F.
1986-08-01
The recoilless fraction is calculated for a number of Mössbauer atoms that are natural constituents of HfC, TaC, NdSb, FeO, NiO, EuO, EuS, EuSe, EuTe, SnTe, PbTe and CsF. The calculations are based on a model developed by Kagan and Maslow for binary compounds with rocksalt structure. With the exception of SnTe and, to a lesser extent, PbTe, the results are in reasonable agreement with the available experimental data and values derived from other models.
Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura.
Cao, Long Bao; Jones, Christopher; Movahed, Assad
2013-04-16
Thrombotic thrombocytopenia purpura (TTP) was first described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.
Astrachan, G D
2000-07-01
This paper attempts to discern a ground for doing depth psychological work in times of disappearance, loss and the absence of the gods. Through the poetry of Friedrich Hölderlin, and to a lesser extent, Rainer Maria Rilke, it seeks to discover the significance of fragmentation and conflagration in the manifestations of both psyche and the post-industrial landscape we inhabit. What does the 'death of god' mean for our notions of symbol and self and for the practice of psychotherapy and psychoanalysis? How do we understand our daily clinical work in the context of ruin, holocaust and despair?
Rock geochemistry in the Mahd adh Dhahab district, Kingdom of Saudi Arabia
Worl, R.G.; Doebrich, J.L.; Allen, M.S.; Afifi, A.M.; Ebens, R.J.
1987-01-01
Anomalous values of gold, silver, lead, and to a lesser extent copper and zinc in surface rock samples clearly delineated the northern mineralized zone in the upper agglomerate, and an east-vein area and west-vein area of the southern mineralized zone in the lower agglomerate. A third geochemically anomalous area occurs farther to the west in the lower agglomerate, suggesting that mineralization may have extended at least to this area along the lower agglomerate-lower tuff contact, and possibly even further to the west.
Analytical solutions to the problem of transient heat transfer in living tissue.
NASA Technical Reports Server (NTRS)
Shitzer, A.; Chato, J. C.
1971-01-01
An analytical model of transient heat transfer in living biological tissue is considered. The model includes storage, generation, conduction, and convective transport of heat in the tissue. Solutions for rectangular and cylindrical coordinates are presented and discussed. Transient times for reaching the ?locally fully developed' temperature profile were found to be of the order of 5 to 25 min. These transients are dominated by a geometrical parameters and, to a lesser extent, by a parameter representing the ratio of heat supplied by blood flow to heat conducted in the tissue.
Measurement of hadron azimuthal distributions in deep inelastic muon proton scattering
NASA Astrophysics Data System (ADS)
Arneodo, M.; Arvidson, A.; Aubert, J. J.; Badelek, B.; Beaufays, J.; Bee, C. P.; Benchouk, C.; Berghoff, G.; Bird, I.; Blum, D.; Böhm, E.; de Bouard, X.; Brasse, F. W.; Braun, H.; Broll, C.; Brown, S.; Brück, H.; Calen, H.; Chima, J. S.; Ciborowski, J.; Clifft, R.; Coignet, G.; Combley, F.; Conrad, J.; Coughlan, J.; D'Agostini, G.; Dahlgren, S.; Dengler, F.; Derado, I.; Dreyer, T.; Drees, J.; Düren, M.; Eckardt, V.; Edwards, A.; Edwards, M.; Ernst, T.; Eszes, G.; Favier, J.; Ferrero, M. I.; Figiel, J.; Flauger, W.; Foster, J.; Gabathuler, E.; Gajewski, J.; Gamet, R.; Gayler, J.; Geddes, N.; Grafström, P.; Grard, F.; Haas, J.; Hagberg, E.; Hasert, F. J.; Hayman, P.; Heusse, P.; Jaffre, M.; Jacholkowska, A.; Janata, F.; Jancso, G.; Johnson, A. S.; Kabuss, E. M.; Kellner, G.; Korbel, V.; Krüger, J.; Kullander, S.; Landgraf, U.; Lanske, D.; Loken, J.; Long, K.; Maire, M.; Malecki, P.; Manz, A.; Maselli, S.; Mohr, W.; Montanet, F.; Montgomery, H. E.; Nagy, E.; Nassalski, J.; Norton, P. R.; Oakham, F. G.; Osborne, A. M.; Pascaud, C.; Pavel, N.; Pawlik, B.; Payre, P.; Peroni, C.; Peschel, H.; Pessard, H.; Pettingale, J.; Pietrzyk, B.; Pönsgen, B.; Pötsch, M.; Renton, P.; Ribarics, P.; Rith, K.; Rondio, E.; Scheer, M.; Sandacz, A.; Schlagböhmer, A.; Schiemann, H.; Schmitz, N.; Schneegans, M.; Scholz, M.; Schröder, T.; Schultze, K.; Sloan, T.; Stier, H. E.; Studt, M.; Taylor, G. N.; Thénard, J. M.; Thompson, J. C.; de La Torre, A.; Toth, J.; Urban, L.; Wallucks, W.; Whalley, M.; Wheeler, S.; Williams, W. S. C.; Wimpenny, S. J.; Windmolders, R.; Wolf, G.
1987-09-01
A study of the distribution of the azimuthal angle ϕ of charged hadrons in deep inelastic μ- p scattering is presented. The dependence of the moments of this distribution on the Feynman x variable and the momentum transverse to the virtual photon indicates that non-zero moments arise mainly from the effects of the intrinsic K T of the struck quark with < K {/T 2}>>≳(0.44 GeV)2, and to a lesser extent from QCD processes. No significant variation with Q 2 or W 2 is observed.
Is Red Heavier Than Yellow Even for Blind?
Barilari, Marco; de Heering, Adélaïde; Crollen, Virginie; Collignon, Olivier; Bottini, Roberto
2018-01-01
Across cultures and languages, people find similarities between the products of different senses in mysterious ways. By studying what is called cross-modal correspondences, cognitive psychologists discovered that lemons are fast rather than slow, boulders are sour, and red is heavier than yellow. Are these cross-modal correspondences established via sensory perception or can they be learned merely through language? We contribute to this debate by demonstrating that early blind people who lack the perceptual experience of color also think that red is heavier than yellow but to a lesser extent than sighted do.
Uribe M , Rosario; Valdivia R , Mario; Carrasco E , Juan
1997-01-01
In 1996, one hundred health histories of HIV serum positive patients were reviewed using the Elisa and Western Blot techniques at the Arzobispo Loayza National Hospital. Such cases were defined according to Case Definition 1987 CDC/WHO. 70% of HIV serum positive patients showed gastrointestinal symptoms according to the first medical examination. 57% of the patients were younger than 30 years old, most of them were men (men/ women ratio: 2.7/1). 59% of the patients were heterosexual, 26% bisexual, and 15% homosexual. Chronic diarrhea was the main symptom, characterized by watering depositions over 10c/d. Giardia lamblia was isolated in 32% of the cases, while Isospora Belli in 16% and Criptosporidium in 12.5%. The laboratory findings of 7 patients (12.5%) were negative. Patients showed more than 10% weight loss. 10% of the patients had an anorectal disease while 7 of the patients (10%) had an hepatic-billiary disease. The odynophagia and dysphagia were explained by oropharyngeal candidiasis. 2.8% of the patients had acalculous cholecystitis; 2.8% suffered from acute pancreatic disease and 1.4% ascitis. The hepatic biochemistry was affected by the serum albumin reduction, the transaminases increase over 2-3 times compared to normal levels and the alkaline phosphatase, bilirrubina was about 5 mg. The high endoscopic diagnostic was in connection to the candida esophagitis and inflammatory pathology. In proctoscopy, condyloma acuminatum and perianal fistula were the most usual findings. The counting of CD4 leukocytes in 20 patients showed a great reduction of CD4 lymphocytes, in values lesser than 200 cel/mm3. The relation CD4/CD8 goes from 0.01 to 0.91 rates.
Lemoine, H.; Schönell, H.; Kaumann, A. J.
1988-01-01
1. (-)-Atenolol was used as a tool to assess the function of beta 1- and beta 2-adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for beta-adrenoceptor labelling with [3H]-(-)-bupranolol and adenylate cyclase assays. 2. The positive inotropic effects of (-)-noradrenaline were antagonized to a similar extent by (-)-atenolol in atrial and ventricular preparations. (-)-Atenolol consistently antagonized the effects of (-)-adrenaline to a lesser extent than those of (-)-noradrenaline in atrial preparations. In ventricular preparations (-)-atenolol antagonized the effects of low concentrations of (-)-adrenaline to a lesser extent than those of high concentrations. 3. pKB values (M) of (-)-atenolol, estimated with non-linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for beta 1-adrenoceptors and 6.0 for beta 2-adrenoceptors. 4. (-)-Atenolol inhibited the binding of [3H]-(-)-bupranolol to ventricular beta 1-adrenoceptors with a pKD (M) of 5.9 and to ventricular beta 2-adrenoceptors with a pKD of 4.6. 5. (-)-Atenolol inhibited the catecholamine-induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8-6.4 for beta 1- and pKB values of 4.7-5.7 for beta 2-adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (-)-atenolol inherent to membrane preparations. 6. beta 1-Adrenoceptors mediate the maximum positive inotropic effects of (-)-noradrenaline in both the atrium and ventricle of man. beta 2-Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (-)-adrenaline in atrium. In contrast, ventricular beta 2-adrenoceptors mediated only submaximal effects of (-)-adrenaline. PMID:2851354
Berghoff, Anna S; Fuchs, Elisabeth; Ricken, Gerda; Mlecnik, Bernhard; Bindea, Gabriela; Spanberger, Thomas; Hackl, Monika; Widhalm, Georg; Dieckmann, Karin; Prayer, Daniela; Bilocq, Amelie; Heinzl, Harald; Zielinski, Christoph; Bartsch, Rupert; Birner, Peter; Galon, Jerome; Preusser, Matthias
2016-01-01
The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). TIL density was not associated with corticosteroid administration (p > 0.05). A significant difference in infiltration density according to TIL subtype was present (p < 0.001; Chi Square); high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8+ TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging (p = 0.031). The density of CD3+ (15 vs. 6 mo; p = 0.015), CD8+ (15 vs. 11 mo; p = 0.030) and CD45RO+ TILs (18 vs. 8 mo; p = 0.006) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo; p < 0.001). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612, p < 0.001). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings. PMID:26942067
Mutoh, Yoshikazu; Nishijima, Takeshi; Inaba, Yosuke; Tanaka, Noriko; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi
2018-03-02
The extent and duration of long-term recovery of CD4 count, CD4%, and CD4/CD8 ratio after initiation of combination antiretroviral therapy (cART) in patients with suppressed viral load are largely unknown. HIV-1 infected patients who started cART between January 2004 and January 2012 and showed persistent viral suppression (<200 copies/mL) for at least 4 years were followed up at AIDS Clinical Center, Tokyo. Change point analysis was used to determine the time point where CD4 count recovery shows a plateau, and linear mixed model was applied to estimate CD4 count at the change point. Data of 752 patients were analyzed [93% males, median age 38, median baseline CD4 count 172/µL (IQR, 62-253), CD4% 13.8% (IQR, 7.7-18.5), and CD4/8 ratio 0.23 (IQR, 0.12-0.35)]. The median follow-up period was 81.2 months and 91 (12.1%) patients were followed for >10 years. Change point analysis showed that CD4 count, CD4%, and CD4/CD8 ratio, continued to increase until 78.6, 62.2, and 64.3 months, respectively, with adjusted mean of 590 /µL (95%CI 572-608), 29.5% (29-30.1), and 0.89 (0.86-0.93), respectively, at the change point. Although 73.8% of the study patients achieved CD4 count ≥500 /μL, 48.2% of the patients with baseline CD4 count <100 /μL did not achieve CD4 count ≥500 /μL. Neither CD4% nor CD4/CD8 ratio normalized in a majority of patients. The results showed lack of normalization of CD4 count, CD4%, and CD4/CD8 ratio to the levels seen in healthy individuals even after long-term successful cART in patients with suppressed viral load.
CD8+ T Cells Cause Disability and Axon Loss in a Mouse Model of Multiple Sclerosis
Schmalstieg, William F.; Sauer, Brian M.; Wang, Huan; German, Christopher L.; Windebank, Anthony J.; Rodriguez, Moses; Howe, Charles L.
2010-01-01
Background The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. Methodology/Principal Findings To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. Conclusions/Significance In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis. PMID:20814579
Veazey, Ronald S.; Mansfield, Keith G.; Tham, Irene C.; Carville, Angela C.; Shvetz, Daniel E.; Forand, Amy E.; Lackner, Andrew A.
2000-01-01
Early viral replication and profound CD4+ T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4+ T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4+ T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a “memory” phenotype (CD45RA−). Following intravenous infection with SIVmac251, memory CD4+ CCR5+ T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4+ T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4+ T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA+). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4+ T cells were found in lymphoid tissues, and all of the remaining CD4+ T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo. PMID:11069995
ADP ribosyl-cyclases (CD38/CD157), social skills and friendship.
Chong, Anne; Malavasi, Fabio; Israel, Salomon; Khor, Chiea Chuen; Yap, Von Bing; Monakhov, Mikhail; Chew, Soo Hong; Lai, Poh San; Ebstein, Richard P
2017-04-01
Why some individuals seek social engagement while others shy away has profound implications for normal and pathological human behavior. Evidence suggests that oxytocin (OT), the paramount human social hormone, and CD38 that governs OT release, contribute to individual differences in social skills from intense social involvement to extreme avoidance that characterize autism. To explore the neurochemical underpinnings of sociality, CD38 expression of peripheral blood leukocytes (PBL) was measured in Han Chinese undergraduates. First, CD38 mRNA levels were correlated with lower Autism Quotient (AQ), indicating enhanced social skills. AQ assesses the extent of autistic-like traits including the propensity and dexterity needed for successful social engagement in the general population. Second, three CD157 eQTL SNPs in the CD38/CD157 gene region were associated with CD38 expression. CD157 is a paralogue of CD38 and is contiguous with it on chromosome 4p15. Third, association was also observed between the CD157 eQTL SNPs, CD38 expression and AQ. In the full model, CD38 expression and CD157 eQTL SNPs altogether account for a substantial 14% of the variance in sociality. Fourth, functionality of CD157 eQTL SNPs was suggested by a significant association with plasma oxytocin immunoreactivity products. Fifth, the ecological validity of these findings was demonstrated with subjects with higher PBL CD38 expression having more friends, especially for males. Furthermore, CD157 sequence variation predicts scores on the Friendship questionnaire. To summarize, this study by uniquely leveraging various measures reveals salient elements contributing to nonkin sociality and friendship, revealing a likely pathway underpinning the transition from normality to psychopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.
D'Souza, Sushila; Romano, Marta; Korf, Johanna; Wang, Xiao-Ming; Adnet, Pierre-Yves; Huygen, Kris
2006-05-01
Reactivation tuberculosis (TB) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (HIV) coinfection. The adaptive immune response mediated by CD4+ and CD8+ T cells is known to confer protection against TB. Hence, vaccines against TB are designed to activate these two components of the immune system. Anti-TB DNA vaccines encoding the immunodominant proteins Ag85A, Ag85B, and PstS-3 from Mycobacterium tuberculosis are ineffective in mice lacking CD4+ T cells (CD4-/- mice). In this study, we demonstrate that reconstitution of the T-cell compartment in CD4-/- mice restores vaccine-specific antibody and gamma interferon (IFN-gamma) responses to these DNA vaccines. The magnitude of the immune responses correlated with the extent of reconstitution of the CD4+-T-cell compartment. Reconstituted mice vaccinated with DNA encoding PstS-3, known to encode a dominant D(b)-restricted CD8+-T-cell epitope, displayed CD8+-T-cell responses not observed in CD4-/- mice. M. tuberculosis challenge in reconstituted mice led to the extravasation of IFN-gamma-producing CD4+ and CD8+ T cells into lungs, the primary site of bacterial replication. Importantly, a reconstitution of 12 to 15% of the CD4+-T-cell compartment resulted in Ag85B plasmid DNA-mediated protection against a challenge M. tuberculosis infection. Our findings provide evidence that anti-TB DNA vaccines could be effective in immunodeficient individuals after CD4+-T-lymphocyte reconstitution, as may occur following antiretroviral therapy in HIV+ patients.
Yun, Xiang; Shang, Yunxiao; Li, Miao
2015-01-01
Bronchial asthma is a chronic airway inflammatory disease that involves T lymphocytes. In order to explore the effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4(+) CD25(+) Foxp3(+) Treg in asthma Balb/c mouse, we constructed acute asthma model with ovalbumin to observe the mouse behavior change in Balb/c mice. The expression of GATA-3 mRNA and T-bet mRNA was measured by real-time PCR. The proportion of CD4(+) CD25(+) Foxp3(+) Treg/CD4(+) was determined by flow cytometry. The results demonstrated that oral gavage with Lactobacillus salivarius before sensitization could alleviate the clinical symptoms, airway hyper-reactivity and airway inflammation in asthma mouse to some extent; Lactobacillus salivarius may improve the imbalance of Th1/Th2 in asthma mouse through increasing the expression of T-bet mRNA at the transcriptional level and inhibiting the expression of GATA-3 mRNA simultaneously. CD4(+) CD25(+) Foxp3(+) Treg cells may be involved in the pathogenesis of bronchial asthma, and may be the upstream regulatory mechanism of the improvement of Th1/Th2 imbalance by Lactobacillus salivarius.
Shurlygina, A V; Mel'nikova, E V; Trufakin, V A
2015-02-01
We studied the chronodependent effect of IL-2 in the experimental model of immunodeficiency, cyclophosphamide-induced immunosuppression in mice. IL-2 in a dose of 100 U/ mouse was administered at 10.00 and 16.00 for 3 days after injection of cyclophosphamide. In contrast to the morning treatment with the cytokine, evening administration produced antiapoptotic effect on splenocytes and stimulated proliferation to a greater extent. This was accompanied by an increase in the number of CD4(+), CD25(+) and CD4(+)25(+) cells in the spleen to a level of intact mice. More pronounced effect of the evening mode of IL-2 administration on the proliferation and subpopulation composition of mouse spleen cells in the studied model can be associated with high blood level of CD25(+) cells at this time of the day.
Mihaylova, Ivana; DeRuyter, Marcel; Rummens, Jean-Luc; Bosmans, Eugene; Maes, Michael
2007-08-01
There is some evidence that patients with chronic fatigue syndrome (CFS) suffer from immune abnormalities, such as immune activation and decreased immune cell responsivity upon polyclonal stimili. This study was designed to evaluate lymphocyte activation in CFS by using a CD69 expression assay. CD69 acts as a costimulatory molecule for T- and natural killer (NK) cell activation. We collected whole blood from CFS patients, who met CDC criteria, and healthy volunteers. The blood samples were stimulated with mitogens during 18 h and the levels of activated T and NK cells expressing CD69 were measured on a Coulter Epics flow cytometer using a three color immunofluorescence staining protocol. The expression of the CD69 activation marker on T cells (CD3+, CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+) was significantly lower in CFS patients than in healthy subjects. These differences were significant to the extent that a significant diagnostic performance was obtained, i.e. the area under the ROC curve was around 89%. No differences either in the number of leukocytes or in the number or percentage of lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found between CFS patients and the controls. Patients with CFS show defects in T- and NK cell activation. Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in CFS there is a disorder in the early activation of the immune system involving PKC.
Alves, Christina S.; Konstantopoulos, Konstantinos
2012-01-01
Fibrin(ogen) mediates sustained tumor cell adhesion and survival in the pulmonary vasculature, thereby facilitating the metastatic dissemination of tumor cells. CD44 is the major functional fibrin receptor on colon carcinoma cells. Growth factors, such as platelet-derived growth factor (PDGF), induce post-translational protein modifications, which modulate ligand binding activity. In view of the roles of PDGF, fibrin(ogen) and CD44 in cancer metastasis, we aimed to delineate the effect of PDGF on CD44-fibrin recognition. By immunoprecipitating CD44 from PDGF-treated and untreated LS174T colon carcinoma cells, which express primarily CD44v, we demonstrate that PDGF enhances the adhesion of CD44v-coated beads to immobilized fibrin. Enzymatic inhibition studies coupled with flow-based adhesion assays and autoradiography reveal that PDGF augments the binding of CD44v to fibrin by significantly attenuating the extent of CD44 sulfation primarily on chondroitin and dermatan sulfate chains. Surface plasmon resonance assays confirm that PDGF enhances the affinity of CD44v-fibrin binding by markedly reducing its dissociation rate while modestly increasing the association rate. PDGF mildly reduces the affinity of CD44v-hyaluronan binding without affecting selectin-CD44v recognition. The latter is attributed to the fact that CD44v binds to selectins via sialofucosylated O-linked residues independent of heparan, dermatan and chondroitin sulfates. Interestingly, PDGF moderately reduces the sulfation of CD44s and CD44s-fibrin recognition. Collectively, these data offer a novel perspective into the mechanism by which PGDF regulates CD44-dependent binding of metastatic colon carcinoma cells to fibrin(ogen). PMID:23056168
Lewis, S M; Treacher, D F; Edgeworth, J; Mahalingam, G; Brown, C S; Mare, T A; Stacey, M; Beale, R; Brown, K A
2015-11-01
There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively. © 2015 British Society for Immunology.
Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B
2009-03-01
To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.
Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.
2012-01-01
Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319
Lee, Shin Wha; Kim, Yong-Man; Lee, Ha-Young; Kim, Dae-Yeon; Kim, Jong-Hyeok; Nam, Joo-Hyun; Kim, Young-Tak
2010-03-01
Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4(+)CD25(high+)Foxp3(+) T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2). Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry. Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4(+) T lymphocytes increased, CD8(+) T lymphocytes decreased, and the proportion of CD3(-)CD16(+)56(+) NK cells was unchanged. The proportion of CD4(+)CD25(high+)Foxp3(+) regulatory T lymphocytes in CD4(+) T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group. This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.
Endoscopy in inflammatory bowel disease when and why
Rameshshanker, Rajaratnam; Arebi, Naila
2012-01-01
Endoscopy plays an important role in the diagnosis and management of inflammatory bowel disease (IBD). It is useful to exclude other aetiologies, differentiate between ulcerative colitis (UC) and Crohn’s disease (CD), and define the extent and activity of inflammation. Ileocolonoscopy is used for monitoring of the disease, which in turn helps to optimize the management. It plays a key role in the surveillance of UC for dysplasia or neoplasia and assessment of post operative CD. Capsule endoscopy and double balloon enteroscopy are increasingly used in patients with CD. Therapeutic applications relate to stricture dilatation and dysplasia resection. The endoscopist’s role is vital in the overall management of IBD. PMID:22720120
Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection
Zhang, Zhi-Qiang; Notermans, Daan W.; Sedgewick, Gerald; Cavert, Winston; Wietgrefe, Stephen; Zupancic, Mary; Gebhard, Kristin; Henry, Keith; Boies, Lawrence; Chen, Zongming; Jenkins, Marc; Mills, Roger; McDade, Hugh; Goodwin, Carolyn; Schuwirth, Caspar M.; Danner, Sven A.; Haase, Ashley T.
1998-01-01
Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1. PMID:9448301
Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection.
Zhang, Z Q; Notermans, D W; Sedgewick, G; Cavert, W; Wietgrefe, S; Zupancic, M; Gebhard, K; Henry, K; Boies, L; Chen, Z; Jenkins, M; Mills, R; McDade, H; Goodwin, C; Schuwirth, C M; Danner, S A; Haase, A T
1998-02-03
Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.
Muñoz-Pinedo, C; Oliver, F J; López-Rivas, A
2001-01-01
Treatment of haematopoietic BA/F3 cells with the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine (FUdR) activated apoptosis through a mechanism that required continuous protein synthesis and was inhibited by Bcl-2 over-expression. Analysis of p53 levels in cells treated with FUdR indicated a marked accumulation of this protein. Accumulation of p53 was also observed in cells over-expressing Bcl-2. In BA/F3 cells transfected with a cDNA coding for the human papilloma virus protein E6, p53 accumulation after FUdR treatment was inhibited markedly. However, apoptosis was induced in both control and E6 cells to a similar extent. The role of the CD95/CD95 ligand (CD95L) system in FUdR-induced apoptosis was also assessed. As determined by reverse transcriptase PCR, BA/F3 expressed a low constitutive level of CD95L mRNA, which decreased following FUdR treatment. Moreover, blocking CD95-CD95L interactions with antagonistic CD95 monoclonal antibody did not prevent drug-induced apoptosis. Furthermore, analysis of caspase involvement showed important differences in apoptosis induced by CD95-triggering or FUdR treatment. In summary, these results suggest that apoptosis induced by thymineless stress in haematopoietic BA/F3 cells occurs by a mechanism that does not require accumulation of p53 and which is independent of CD95-CD95L interactions. PMID:11115403
Lancioni, Christina L; Thomas, Jeremy J; Rojas, Roxana E
2009-05-15
Direct regulation of T cell function by microbial ligands through Toll-like receptors (TLR) is an emerging area of T cell biology. Currently either immunomagnetic cell sorting (IMACS) or fluorescence-activated cell sorting (FACS), are utilized to isolate T-cell subsets for such studies. However, it is unknown to what extent differences in T cell purity between these isolation techniques influence T cell functional assays. We compared the purity, response to mitogen, activation requirements, and response to TLR ligands between human CD4(+) T cells isolated either by IMACS (IMACS-CD4(+)) or by IMACS followed by FACS (IMACS/FACS-CD4(+)). As expected, IMACS-CD4(+) were less pure than IMACS/FACS-CD4(+) (92.5%+/-1.4% versus 99.7%+/-0.2%, respectively). Consequently, IMACS-CD4(+) proliferated and produced cytokines in response to mitogen alone and had lower activation requirements compared to IMACS/FACS-CD4(+). In addition IMACS-CD4(+) but not IMACS/FACS-CD4(+) responses were upregulated by the TLR-4 ligand lipopolysaccharide (LPS). On the other hand, TLR-2 and TLR-5 engagement induced costimulation in both IMACS-CD4(+) and highly purified IMACS-/FACS-CD4(+). Altogether these results indicate that small differences in cell purity can significantly alter T cell responses to TLR ligands. This study stresses the importance of a stringent purification method when investigating the role of microbial ligands in T cell function.
Medina, A; Vassilev, N; Barea, J M; Azcón, R
2005-04-06
The microbial transformation of sugar beet (SB) agrowaste with or without rock-phosphate (RP) has utility for the improvement of plant growth in a Cd (5 microg g-1) artificially contaminated soil, particularly when the soil is co-inoculated with arbuscular mycorrhizal (AM) fungus Glomus mosseae isolated from a Cd-polluted area. Under such Cd-polluted conditions, the limited growth, mineral nutrition, symbiotic developments (nodulation and AM-colonization) and soil enzymatic activities were stimulated using SB or SB+RP as soil amendments and G. mosseae as inoculant. G. mosseae enhanced plant establishment in a higher extent in amended soil; it is probably due to the interactive effect increasing the potential fertility of such compounds and its ability for decreasing Cd transfer from soil to plant. The amount of Cd transferred from soil solution to biomass of AM-colonized plants ranged from 0.09 microg Cd g-1 (in SB+RP-amended soil) to 0.6 microg Cd g-1 (in non-amended soil). Nodule formation was more sensitive to Cd than AM-colonization, and both symbioses were stimulated in amended soils. Not only AM-colonization but also amendments were critical for plant growth and nutrition in Cd-polluted soil. The high effectiveness of AM inoculum increasing nutrients and decreasing Cd in amended soil indicated the positive interaction of these treatments in increasing plant tolerance to Cd contamination.
CD47-ligation induced cell death in T-acute lymphoblastic leukemia.
Leclair, Pascal; Liu, Chi-Chao; Monajemi, Mahdis; Reid, Gregor S; Sly, Laura M; Lim, Chinten James
2018-05-10
CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death. Here, we describe a commercially available mAb, CC2C6, which induces T-cell acute lymphoblastic leukemia (ALL) cell death in soluble form. Soluble CC2C6 induces CD47-dependent cell death in a manner consistent with immobilized B6H12, which is characterized by mitochondrial deficiencies but is independent of caspase activation. Titration studies indicated that CC2C6 shares a common CD47-epitope with B6H12. Importantly, CC2C6 retains the anti-phagocytic neutralizing function, thus possessing dual anti-tumour properties. Although CD47-ligation induced cell death occurs in a caspase-independent manner, CC2C6 was found to stimulate increases in Mcl-1 and NOXA levels, two Bcl-2 family proteins that govern the intrinsic apoptosis pathway. Further analysis revealed that the ratio of Mcl-1:NOXA were minimally altered for cells treated with CC2C6, in comparison to cells treated with agents that induced caspase-dependent apoptosis which alter this ratio in favour of NOXA. Finally, we found that CC2C6 can synergize with low dose chemotherapeutic agents that induce classical apoptosis, giving rise to the possibility of an effective combination treatment with reduced long-term sequelae associated with high-dose chemotherapies in childhood ALL.
Muench, Marcus O.; Beyer, Ashley I.; Fomin, Marina E.; Thakker, Rahul; Mulvaney, Usha S.; Nakamura, Masato; Suemizu, Hiroshi; Bárcena, Alicia
2014-01-01
The liver plays a vital role in hematopoiesis during mammalian prenatal development but its hematopoietic output declines during the perinatal period. Nonetheless, hepatic hematopoiesis is believed to persist into adulthood. We sought to model human adult-liver hematopoiesis by transplantation of fetal and neonatal hematopoietic stem cells (HSCs) into adult immunodeficient mice. Livers were found to be engrafted with human cells consisting primarily of monocytes and B-cells with lesser contributions by erythrocytes, T-cells, NK-cells and mast-cells. A resident population of CD117++CD203c+ mast cells was also documented in human midgestation liver, indicating that these cells comprise part of the liver's resident immune cell repertoire throughout human ontogeny. The murine liver was shown to support human multilineage hematopoiesis up to 321 days after transplant. Evidence of murine hepatic hematopoiesis was also found in common mouse strains as old as 2 years. Human HSC engraftment of the murine liver was demonstrated by detection of high proliferative-potential colony-forming cells in clonal cultures, observation of CD38−CD34++ and CD133+CD34++ cells by flow cytometry, and hematopoietic reconstitution of secondary transplant recipients of chimeric liver cells. Additionally, chimeric mice with both hematopoietic and endothelial reconstitution were generated by intrasplenic injection of immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA) transgene. In conclusion, the murine liver is shown to be a hematopoietic organ throughout adult life that can also support human hematopoiesis in severely immunodeficient strains. Further humanization of the murine liver can be achieved in mice harboring an uPA transgene, which support engraftment of non-hematopoietic cells types. Thus, offering a model system to study the interaction of diverse human liver cell types that regulate hematopoiesis and immune function in the liver. PMID:24819392
Surface complexation modeling of proton and Cd adsorption onto an algal cell wall.
Kaulbach, Emily S; Szymanowski, Jennifer E S; Fein, Jeremy B
2005-06-01
This study quantifies Cd adsorption onto the cell wall of the algal species Pseudokirchneriella subcapitata by applying a surface complexation approach to model the observed adsorption behavior. We use potentiometric titrations to determine deprotonation constants and site concentrations for the functional groups on the algal cell wall. Adsorption and desorption kinetics experiments illustrate that adsorption of Cd onto the cell wall is rapid and reversible, except under low pH conditions. Adsorption experiments conducted as a function of pH and total Cd concentration yield the stoichiometry and site-specific stability constants for the important Cd-algal surface complexes. We model the acid/base properties of the algal cell wall by invoking four discrete surface functional group types, with pKa values of 3.9 +/- 0.3, 5.4 +/- 0.1, 7.6 +/- 0.3, and 9.6 +/- 0.4. The results of the Cd adsorption experiments indicate that the first, third, and fourth sites contribute to Cd adsorption under the experimental conditions, with calculated log stability constant values of 4.1 +/- 0.5, 5.4 +/- 0.5, and 6.1 +/- 0.4, respectively. Our results suggest that the stabilities of the Cd-surface complexes are high enough for algal adsorption to affect the fate and transport of Cd under some conditions and that on a per gram basis, algae and bacteria exhibit broadly similar extents of Cd adsorption.
Stadnik, Ryan D; Brand, Bethany; Savoca, Angela
2013-01-01
Assessing patients with dissociative disorders (DD) using personality tests is difficult. On the Minnesota Multiphasic Personality Inventory-2 ( J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989 ), DD patients often obtain elevations on multiple clinical scales as well as on validity scales that were thought to indicate exaggeration yet have been shown to be elevated among traumatized individuals, including those with DD. No research has been conducted to determine how DD patients score on the Personality Assessment Inventory (PAI; L. C. Morey, 1991 ), which includes the symptom exaggeration scale Negative Impression (NIM) and the malingering scales Malingering Index (MAL) and Rogers Discriminant Function (RDF). The goals of this study were to document the PAI profile of dissociative identity disorder (DID) and dissociative disorder not otherwise specified (DDNOS) patients and to determine how the validity and Schizophrenia scales are related to other PAI scales as well as dissociation. A total of 42 inpatients with DID or DDNOS were assessed on the PAI as well as the Dissociative Experiences Scale-II. The DID/DDNOS patients were elevated on many PAI scales, including NIM and, to a lesser extent, MAL, but not RDF. Dissociation scores significantly and uniquely predicted NIM scores above and beyond Depression and Borderline Features. In addition, after we controlled for MAL and RDF, dissociation was positively associated with NIM. In contrast, after we controlled for the other 2 scales, dissociation was not related to MAL and was negatively related to RDF, indicating that RDF and, to a lesser extent, MAL are better correlates of feigning in DD patients than NIM.
Work, Timothy T.; Klimaszewski, Jan; Thiffault, Evelyne; Bourdon, Caroline; Paré, David; Bousquet, Yves; Venier, Lisa; Titus, Brian
2013-01-01
Abstract Increased interest in biomass harvesting for bioenergetic applications has raised questions regarding the potential ecological consequences on forest biodiversity. Here we evaluate the initial changes in the abundance, species richness and community composition of rove (Staphylinidae) and ground beetles (Carabidae), immediately following 1) stem-only harvesting (SOH), in which logging debris (i.e., tree tops and branches) are retained on site, and 2) whole-tree harvesting (WTH), in which stems, tops and branches are removed in mature balsam fir stands in Quebec, Canada. Beetles were collected throughout the summer of 2011, one year following harvesting, using pitfall traps. Overall catch rates were greater in uncut forest (Control) than either stem-only or whole-tree harvested sites. Catch rates in WTH were greater than SOH sites. Uncut stands were characterized primarily by five species: Atheta capsularis, Atheta klagesi, Atheta strigosula, Tachinus fumipennis/frigidus complex (Staphylinidae) and to a lesser extent to Pterostichus punctatissimus (Carabidae). Increased catch rates in WTH sites, where post-harvest biomass was less, were attributable to increased catches of rove beetles Pseudopsis subulata, Quedius labradorensis and to a lesser extent Gabrius brevipennis. We were able to characterize differences in beetle assemblages between harvested and non-harvested plots as well as differences between whole tree (WTH) and stem only (SOH) harvested sites where logging residues had been removed or left following harvest. However, the overall assemblage response was largely a recapitulation of the responses of several abundant species. PMID:23653498
Work, Timothy T; Klimaszewski, Jan; Thiffault, Evelyne; Bourdon, Caroline; Paré, David; Bousquet, Yves; Venier, Lisa; Titus, Brian
2013-01-01
Increased interest in biomass harvesting for bioenergetic applications has raised questions regarding the potential ecological consequences on forest biodiversity. Here we evaluate the initial changes in the abundance, species richness and community composition of rove (Staphylinidae) and ground beetles (Carabidae), immediately following 1) stem-only harvesting (SOH), in which logging debris (i.e., tree tops and branches) are retained on site, and 2) whole-tree harvesting (WTH), in which stems, tops and branches are removed in mature balsam fir stands in Quebec, Canada. Beetles were collected throughout the summer of 2011, one year following harvesting, using pitfall traps. Overall catch rates were greater in uncut forest (Control) than either stem-only or whole-tree harvested sites. Catch rates in WTH were greater than SOH sites. Uncut stands were characterized primarily by five species: Atheta capsularis, Atheta klagesi, Atheta strigosula, Tachinus fumipennis/frigidus complex (Staphylinidae) and to a lesser extent to Pterostichus punctatissimus(Carabidae). Increased catch rates in WTH sites, where post-harvest biomass was less, were attributable to increased catches of rove beetles Pseudopsis subulata, Quedius labradorensis and to a lesser extent Gabrius brevipennis. We were able to characterize differences in beetle assemblages between harvested and non-harvested plots as well as differences between whole tree (WTH) and stem only (SOH) harvested sites where logging residues had been removed or left following harvest. However, the overall assemblage response was largely a recapitulation of the responses of several abundant species.
Neural Correlates of Emotion Regulation in Patients with Schizophrenia and Non-Affected Siblings
van der Velde, Jorien; Pijnenborg, Gerdina; Wiersma, Durk; Bruggeman, Richard; Aleman, André
2014-01-01
Background Patients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC) exhibit differences in brain activation during emotion regulation. Methods All subjects (n = 20 per group) performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress), in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ). Results Though the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas. Conclusions Given that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis. PMID:24941136
Lu, Zhibing; Feng, Xiaohua; Song, Ling; Han, Ying; Kim, Alexander; Herzberg, Osnat; Woodson, William R; Martin, Brian M; Mariano, Patrick S; Dunaway-Mariano, Debra
2005-12-20
The work described in this paper was carried out to define the chemical function a new member of the isocitrate lyase enzyme family derived from the flowering plant Dianthus caryophyllus. This protein (Swiss-Prot entry Q05957) is synthesized in the senescent flower petals and is named the "petal death protein" or "PDP". On the basis of an analysis of the structural contexts of sequence markers common to the C-C bond lyases of the isocitrate lyase/phosphoenolpyruvate mutase superfamily, a substrate screen that employed a (2R)-malate core structure was designed. Accordingly, stereochemically defined C(2)- and C(3)-substituted malates were synthesized and tested as substrates for PDP-catalyzed cleavage of the C(2)-C(3) bond. The screen identified (2R)-ethyl, (3S)-methylmalate, and oxaloacetate [likely to bind as the hydrate, C(2)(OH)(2) gem-diol] as the most active substrates (for each, k(cat)/K(m) = 2 x 10(4) M(-)(1) s(-)(1)). In contrast to the stringent substrate specificities previously observed for the Escherichia coli isocitrate and 2-methylisocitrate lyases, the PDP tolerated hydrogen, methyl, and to a much lesser extent acetate substituents at the C(3) position (S configuration only) and hydoxyl, methyl, ethyl, propyl, and to a much lesser extent isobutyl substituents at C(2) (R configuration only). It is hypothesized that PDP functions in oxalate production in Ca(2+) sequestering and/or in carbon scavenging from alpha-hydroxycarboxylate catabolites during the biochemical transition accompanying petal senescence.
Gray, Vanessa C; Hughes, Robert N
2015-03-15
In an effort to address the need to include both sexes in studies of effects of the SSRI fluoxetine, the NRI reboxetine and the SNRI venlafaxine on anxiety-related behavior and memory along with the use of chronic drug administration, male and female PVG/c rats were fed diets containing two doses of each drug for 21 days. The rats' anxiety level was then assessed in an open field. Short-term spatial memory for a brightness change in a Y maze was also measured. While there was little evidence of anxiolytic effects of any of the drugs, both fluoxetine and, to a lesser extent, venlafaxine appeared to be mainly anxiogenic in their action depending on both dose and sex. Reboxetine was relatively ineffective in this respect. Ability to locate the Y-maze arm that had changed (from white to black) seemed to be impaired for male (but not female) rats by both fluoxetine and venlafaxine and, to a much lesser extent, by reboxetine. Given the relative ineffectiveness of reboxetine in either test, it is possible that the effects of the other two drugs on both anxiety and memory were mainly due to their serotonin reuptake inhibiting properties. The differences that occurred between males and females in responsiveness to all three drugs supported the long-held view that both sexes should be investigated in studies of this sort, especially in view of reports of sex differences in effects of clinically prescribed antidepressants. Copyright © 2014 Elsevier B.V. All rights reserved.
Hussain, S; Devers-Lamrani, M; Spor, A; Rouard, N; Porcherot, M; Beguet, J; Martin-Laurent, F
2013-03-01
The temporal and spatial variability of the activity of soil microorganisms able to mineralize the herbicide isoproturon (IPU) pesticide was investigated over a three-year long crop rotation between 2008 and 2010. Isoproturon mineralization was higher in 2008, when winter wheat was treated with this herbicide, than in 2009 and 2010, when rape seed and barley were treated with different herbicides. Under laboratory conditions, we showed that isoproturon mineralization was not promoted by sulfonylurea herbicide applied on barley crop in 2010. IPU mineralization was shown to be highly variable at the field scale in years 2009 and 2010. Principal component analyses and analyses of similarities revealed that soil pH and equivalent humidity, and to a lesser extent soil organic matter content and cation exchange capacity (CEC) were the main drivers of isoproturon-mineralizing activity variance. Using a rather simple model that yields the rate of isoproturon mineralization as a function of soil pH and equivalent humidity, we explained up to 85% of the variance observed. Mapping field-scale distribution of isoproturon mineralization over the three-year survey indicated higher variability in 2009 and in 2010 as compared to 2008, suggesting that isoproturon treatment applied to winter wheat promoted isoproturon mineralization activity and reduced its spatial variability. Field-scale distribution of isoproturon mineralization showed important similarity to the distribution of soil pH, equivalent humidity and to a lesser extent to soil organic matter and cation exchange capacity (CEC) thereby confirming our model. Copyright © 2012 Elsevier Ltd. All rights reserved.
Spatio-temporal analysis of preterm birth in Portugal and its relation with environmental variables
NASA Astrophysics Data System (ADS)
Oliveira, M.; Teodoro, Ana C.; Freitas, A.; Bernardes, J.; Gonçalves, H.
2016-10-01
Preterm birth (PTB), one of the major concerns in obstetrics, is conventionally defined as the delivery of a live infant before 37 completed weeks of gestation, and one of its causes may be environmental factors. Remote sensing is a valuable approach for monitoring environmental variables, including in health sciences. In this work, remote sensing data were used to explore the relation of the environment with PTB. Time-series with monthly rates of male/female ratio and PTB were obtained from Portugal in 2000-2014. The environmental variables included in this study were monthly mean temperatures (T), relative humidity (RH), NDVI, concentrations of NO2 and PM10 in 2003-2008. A temporal and spatial analysis of each health-related and environmental variable was performed, as well as their correlation. PTB has been increasing over time, from below 5% in 2000 to around 7% in 2014, with predominance of higher rates in districts with larger population. From 2003 to 2008, T and PM10 decreased significantly. A positive and significant correlation was found between male/female ratio and NO2 and RH, and to a lesser extent with PM10 and NDVI. PTB was also positively and significantly correlated with NO2 and T, and to a lesser extent with RH and PM10. These preliminary results suggest an association of PTB with most of the environmental variables studied, showing that more polluted and populated districts have higher rates of PTB. Further studies are warranted to explore interaction between the considered environmental factors and other variables related with risk for PTB.
Anda, Angéla; Illés, Bernadett; Soós, G
2013-12-01
The aim of the study was to analyse the effect of atmospheric cadmium (Cd) pollution of atmospheric origin in maize compared to a control without Cd pollution. The plant parameters investigated were the timing of phenological phases, leaf area index (LAI) and yield, while radiation and water regime parameters were represented by albedo (reflection grade) and evapotranspiration, respectively. In treatments with and without irrigation, Cd caused a significant reduction in LAI, accompanied by lower evapotranspiration. The mean annual albedo in the Cd-polluted treatment only rose to a moderate extent in 2011 (in 2010 there was hardly any change), but changes within the year were more pronounced in certain phases of development. Cd led to greater reflection of radiation by plants during the vegetative phase, so the radiation absorption of the canopy was reduced leading to a lower level of evapotranspiration. In the dry, hot year of 2011 maize plants in the non-irrigated treatments showed a substantial reduction in grain dry matter, but maize yield losses could be reduced by irrigation in areas exposed to Cd pollution.
Martina, M N; Ramirez Bajo, M J; Bañon-Maneus, E; Moya Rull, D; Hierro-Garcia, N; Revuelta, I; Campistol, J M; Rovira, J; Diekmann, F
2016-11-01
Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27 + CD24 + phenotype was not modified by any immunosuppressive treatment. Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation. Copyright © 2016. Published by Elsevier Inc.
Recent Northern Hemisphere snow cover extent trends and implications for the snow-albedo feedback
NASA Astrophysics Data System (ADS)
Déry, Stephen J.; Brown, Ross D.
2007-11-01
Monotonic trend analysis of Northern Hemisphere snow cover extent (SCE) over the period 1972-2006 with the Mann-Kendall test reveals significant declines in SCE during spring over North America and Eurasia, with lesser declines during winter and some increases in fall SCE. The weekly mean trend attains -1.28, -0.78, and -0.48 × 106 km2 (35 years)-1 over the Northern Hemisphere, North America, and Eurasia, respectively. The standardized SCE time series vary and trend coherently over Eurasia and North America, with evidence of a poleward amplification of decreasing SCE trends during spring. Multiple linear regression analyses reveal a significant dependence of the retreat of the spring continental SCE on latitude and elevation. The poleward amplification is consistent with an enhanced snow-albedo feedback over northern latitudes that acts to reinforce an initial anomaly in the cryospheric system.
A review of studies of the effect of severe malnutrition on mental development.
Grantham-McGregor, S
1995-08-01
This is a review of studies on the relationship between mental development and severe malnutrition. School-age children who suffered from early childhood malnutrition have generally been found to have poorer IQ levels, cognitive function, school achievement and greater behavioral problems than matched controls and, to a lesser extent, siblings. The disadvantages last at least until adolescence. There is no consistent evidence of a specific cognitive deficit. The evidence of a causal relationship is strong but not unequivocal because of difficulties in interpreting retrospective case control studies. Marked improvements in development can occur after adoption or intervention. Therefore, the outcome depends to a large extent on the quality of the subsequent environment. It is likely that extremely deprived environments would exacerbate the effects. There is limited evidence that other nutritional deficiencies may interact with previous malnutrition in affecting cognition. The mechanism linking malnutrition to poor development is still not established.
Maltby, Tomas
2013-04-01
Focusing on gas, this article explores the role of the European Commission in the process of European Union energy security policy development, and the extent to which the policy area is becoming increasingly supranational. Situating the article within the literature on agenda-setting and framing, it is argued that a policy window was opened as a result of: enlargement to include more energy import dependent states, a trend of increasing energy imports and prices, and gas supply disruptions. From the mid-2000s, the Commission contributed to a shift in political norms, successfully framing import dependency as a problem requiring an EU-level solution, based on the institution's pre-existing preferences for a diversified energy supply and internal energy market. Whilst Member States retain significant sovereignty, the Commission has achieved since 2006 creeping competencies in the internal, and to a lesser extent external, dimensions of EU energy policy.