bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytomegalovirus-Infected Human Endothelial Cells Can Stimulate Allogeneic CD4+ Memory T Cells by Releasing Antigenic Exosomes
Authors: Walker Jason D. , Maier Cheryl L. , Pober Jordan S.
Published: April 2014

Human CMV infection is controlled by T cell-mediated immunity and in immunosuppressed transplant patients it is associated with acute allograft rejection as well as chronic allograft vasculopathy. CMV infects endothelial cells (EC) and it is thought that CMV-specific host immune responses to infected allograft EC contribute to rejection. In vitro, CD4+ T cells from CMV-positive donors (but not CMV-negative donors) are readily activated by CMV-infected allogeneic EC, although it is unclear how allogeneic CMV-infected EC activate self-class II MHC-restricted memory CD4+ T cells. In this study, we confirm that purified CD4+ T cells from CMV+ donors are activated by allogeneic CMV-infected EC, but find that the response is dependent upon copurified APC expressing class II MHC that are autologous to the T cells. The transfer of CMV Ags from infected EC to APC can be mediated by EC-derived exosome-like particles. These results provide a mechanism by which CMV can exacerbate allograft rejection and suggest a novel function of EC-derived exosomes that could contribute in a more general manner to immune surveillance.
Acute Alcohol Intoxication Inhibits the Lineage−c-kit+Sca-1+ Cell Response to Escherichia coli Bacteremia
Authors: Zhang Ping , Welsh David A. , Siggins Robert W. , Bagby Gregory J. , Raasch Caroline E. , Happel Kyle I. , Nelson Steve
Published: April 2014

Alcohol abuse predisposes the host to bacterial infections. In response to bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for enhancing host defense. This study investigated the hematopoietic precursor cell response to bacteremia and how alcohol affects this response. Acute alcohol intoxication was induced in BALB/c mice 30 min before initiation of Escherichia coli bacteremia. Bacteremia caused a significant increase in the number of bone marrow lineage (lin−)-c-kit+Sca-1+ cells. Marrow lin−c-kit+Sca-1+ cells isolated from bacteremic mice showed an increase in CFU-granulocyte/macrophage activity compared with controls. In addition to enhanced proliferation of lin−c-kit+Sca-1+ cells as reflected by BrdU incorporation, phenotypic inversion of lin−c-kit+Sca-1+Sca-1− cells primarily accounted for the rapid increase in marrow lin−c-kit+Sca-1+ cells following bacteremia. Bacteremia increased plasma concentration of TNF-α. Culture of marrow lin−c-kit+Sca-1+Sca-1− cells with murine rTNF-α for 24 h caused a dose-dependent increase in conversion of these cells to lin−c-kit+Sca-1+ cells. Sca-1 mRNA expression by the cultured cells was also up-regulated following TNF-α stimulation. Acute alcohol intoxication inhibited the increase in the number of lin−c-kit+Sca-1+ cells in the bone marrow after E. coli infection. Alcohol impeded the increase in BrdU incorporation into marrow lin−c-kit+Sca-1+ cells in response to bacteremia. Alcohol also suppressed the plasma TNF-α response to bacteremia and inhibited TNF-α-induced phenotypic inversion of lin−c-kit+Sca-1+Sca-1− cells in vitro. These data show that alcohol inhibits the hematopoietic precursor cell response to bacteremia, which may serve as one mechanism underlying the impaired host defense in alcohol abusers with severe bacterial infections.
Eosinophil Deficiency Compromises Parasite Survival in Chronic Nematode Infection
Authors: Fabre Valeria , Beiting Daniel P. , Bliss Susan K. , Gebreselassie Nebiat G. , Gagliardo Lucille F. , Lee Nancy A. , Lee James J. , Appleton Judith A.
Published: April 2014

Immune responses elicited by parasitic worms share many features with those of chronic allergy. Eosinophils contribute to the inflammation that occurs in both types of disease, and helminths can be damaged or killed by toxic products released by eosinophils in vitro. Such observations inform the widely held view that eosinophils protect the host against parasitic worms. The mouse is a natural host for Trichinella spiralis, a worm that establishes chronic infection in skeletal muscle. We tested the influence of eosinophils on T. spiralis infection in two mouse strains in which the eosinophil lineage is ablated. Eosinophils were prominent in infiltrates surrounding infected muscle cells of wild-type mice; however, in the absence of eosinophils T. spiralis muscle larvae died in large numbers. Parasite death correlated with enhanced IFN-γ and decreased IL-4 production. Larval survival improved when mice were treated with inhibitors of inducible NO synthase, implicating the NO pathway in parasite clearance. Thus, the long-standing paradigm of eosinophil toxicity in nematode infection requires reevaluation, as our results suggest that eosinophils may influence the immune response in a manner that would sustain chronic infection and insure worm survival in the host population. Such a mechanism may be deployed by other parasitic worms that depend upon chronic infection for survival.
Is Porphyromonas gingivalis Cell Invasion Required for Atherogenesis? Pharmacotherapeutic Implications
Authors: Amar Salomon , Wu Shou-chieh , Madan Monika
Published: April 2014

Various studies have demonstrated an association between chronic bacterial infections and atherosclerotic cardiovascular disease. Porphyromonas gingivalis, which can invade endothelial cells, is one pathogen that may link these disorders. If so, antibiotics that block its invasiveness may ameliorate atherosclerotic plaque progression. To explore the role of invasion of P. gingivalis in inflammation- and infection-associated atherosclerosis, 10-wk-old ApoE+/− mice were fed either a high fat diet or a regular chow diet. All mice were inoculated i.v., once per week for 24 consecutive wk, with either 50 μl of live P. gingivalis (strain 381) (107 CFU); a fimbria-deficient P. gingivalis; or metronidazole before P. gingivalis. Mice were euthanized and evaluated 24 wk after the first inoculation. ApoE+/− mice injected with DPG3 or metronidazole showed significantly fewer atheromatous lesions in the proximal aorta and the aortic tree compared with ApoE+/− mice injected with wild-type P. gingivalis for either diet condition. Serum amyloid A levels were significantly lower in ApoE+/− mice that received either DPG3 or metronidazole before P. gingivalis than from ApoE+/− mice that received P. gingivalis alone. Serum cytokine analysis revealed decreased levels of proinflammatory cytokines in both DPG3-injected and metronidazole/P. gingivalis-treated ApoE+/− mice compared with mice receiving only P. gingivalis, irrespective of diet. P. gingivalis invasion is a critical phenomenon in the progression of atherosclerosis. The present data offer new insights into the pathophysiological pathways involved in atherosclerosis and pave the way for new pharmacological interventions aimed at reducing atherosclerosis.
Novel Chlamydia muridarum T Cell Antigens Induce Protective Immunity against Lung and Genital Tract Infection in Murine Models
Authors: Yu Hong , Jiang Xiaozhou , Shen Caixia , Karunakaran Karuna P. , Brunham Robert C.
Published: April 2014

Using a combination of affinity chromatography and tandem mass spectrometry, we recently identified 8 MHC class II (I-Ab) -bound Chlamydia peptides eluted from dendritic cells (DCs) infected with Chlamydia muridarum. In this study we cloned and purified the source proteins that contained each of these peptides and determined that three of the eight peptide/protein Ags were immunodominant (PmpG-1, RplF, and PmpE/F-2) as identified by IFN-γ ELISPOT assay using splenocytes from C57BL/6 mice recovered from C. muridarum infection. To evaluate whether the three immunodominant Chlamydia protein Ags were also able to protect mice against Chlamydia infection in vivo, we adoptively transferred LPS-matured DCs transfected ex vivo with the cationic liposome DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate) and individual PmpG-1(25–500aa), RplF, or PmpE/F-2 (25–575 aa) proteins. The results showed that the transfected Chlamydia proteins were efficiently delivered intracellularly into DCs. Mice vaccinated with DCs transfected with individual Chlamydia protein PmpG-125–500, RplF, or PmpE/F-225–575 exhibited significant resistance to challenge infection as indicated by reduction in the median Chlamydia inclusion forming units in both the lung and genital tract models. The major outer membrane protein was used as a reference Ag but conferred significant protection only in the genital tract model. Overall, vaccination with DCs transfected with PmpG-125–500 exhibited the greatest degree of protective immunity among the four Chlamydia Ags tested. This study demonstrates that T cell peptide Ags identified by immunoproteomics can be successfully exploited as T cell protein-based subunit vaccines and that PmpG-125–500 protein may be a suitable vaccine candidate for further evaluation.
TSLP Conditions the Lung Immune Environment for the Generation of Pathogenic Innate and Antigen-Specific Adaptive Immune Responses
Authors: Headley Mark B. , Zhou Baohua , Shih Weihui X. , Aye Theingi , Comeau Michael R. , Ziegler Steven F.
Published: April 2014

Thymic stromal lymphopoietin (TSLP) is crucial for the development of atopic diseases in humans and mice. Mice that express a lung-specific TSLP transgene (surfactant protein C promoter (SPC)-TSLP) develop a spontaneous and progressive asthma-like disease, suggesting that TSLP expression alone was sufficient for disease development. In this study, we show that, in fact, TSLP alone only causes a weak innate response that is insufficient for development of full airway inflammatory disease. Complete disease development requires both TSLP and antigenic stimulation. These data suggest that the spontaneous lung inflammation observed in SPC-TSLP mice reflects a TSLP-driven predisposition toward the development of aberrant responses against innocuous environmental Ags. This provides evidence that TSLP may act directly to induce susceptibility to the inappropriate allergic responses that characterize atopy and asthma. We additionally show that disease development requires CD4 T cells but not B cells. Further, we reveal a TSLP-driven innate response involving mucus overproduction and goblet cell metaplasia. Taken together, these data suggest a multifaceted model of TSLP-mediated airway inflammation, with an initial activation of resident innate immune cells, followed by activation of the adaptive immune system and full disease development. This study provides new insight into the unique features of the asthma pathology contributed by the innate and adaptive immune responses in response to TSLP stimulation.
IL-17 Signaling for mRNA Stabilization Does Not Require TNF Receptor-Associated Factor 6
Authors: Hartupee Justin , Liu Caini , Novotny Michael , Sun Dongxu , Li Xiaoxia , Hamilton Thomas A.
Published: April 2014

IL-17 alone is a relatively weak inducer of gene expression, but cooperates with other cytokines, including TNF-α, to generate a strong response in part via prolongation of mRNA t1/2. Because TNFR-associated factor 6 (TRAF6) has been reported to be essential for signaling by IL-17, we examined its involvement in IL-17-mediated mRNA stabilization. Although overexpression of TRAF6 in HeLa cells activates NF-κB, it does not stabilize transfected KC mRNA. Furthermore, a dominant-negative TRAF6 abrogates NF-κB activation, but does not block IL-17-induced chemokine mRNA stabilization. IL-17 can stabilize KC and MIP-2 mRNAs comparably in TNF-α-treated mouse embryo fibroblasts from TRAF6+/+ and TRAF6−/− mice. TRAF6 is known to couple upstream signals with activation of p38 MAPK and mitogen activated protein kinase activated protein kinase 2, both of which have been shown to be important for Toll/IL-1R-mediated mRNA stabilization in various cell types. Inhibition of p38 MAPK, however, does not block IL-17-induced KC mRNA stabilization, and IL-17 can stabilize KC mRNA equally in mouse embryo fibroblasts from both wild-type and mitogen activated protein kinase activated protein kinase 2/3 doubly-deficient mice. Finally, IL-17 can amplify the levels of multiple TNF-α-stimulated mRNAs in wild-type and TRAF6-deficient cells, but not in cells from Act1−/− mice. Collectively, these findings demonstrate the existence of a TRAF6/p38 MAPK-independent pathway that couples the IL-17R with enhanced mRNA stability. Because the most potent effects of IL-17 on gene expression are obtained in cooperation with other cytokines such as TNF-α, these findings suggest that this pathway is a major contributing mechanism for response to IL-17.
Novel Autoantibodies against the Activated Coagulation Factor IX (FIXa) in the Antiphospholipid Syndrome That Interpose the FIXa Regulation by Antithrombin
Authors: Yang Yao-Hsu , Chien Daniel , Wu Meifang , FitzGerald John , Grossman Jennifer M. , Hahn Bevra H. , Hwang Kwan-Ki , Chen Pojen P.
Published: April 2014

We previously reported that some human antiphospholipid Abs (aPL) in patients with the antiphospholipid syndrome (APS) bind to the homologous enzymatic domains of thrombin and the activated coagulation factor X (FXa). Moreover, some of the reactive Abs are prothrombotic and interfere with inactivation of thrombin and FXa by antithrombin (AT). Considering the enzymatic domain of activated coagulation factor IX (FIXa) is homologous to those of thrombin and FXa, we hypothesized that some aPLs in APS bind to FIXa and hinder AT inactivation of FIXa. To test this hypothesis, we searched for IgG anti-FIXa Abs in APS patients. Once the concerned Abs were found, we studied the effects of the Ab on FIXa inactivation by AT. We found that 10 of 12 patient-derived monoclonal IgG aPLs bound to FIXa and that IgG anti-FIXa Abs in APS patients were significantly higher than those in normal controls (p < 0.0001). Using the mean + 3 SD of 30 normal controls as the cutoff, the IgG anti-FIXa Abs were present in 11 of 38 (28.9%) APS patients. Importantly, 4 of 10 FIXa-reactive monoclonal aPLs (including the B2 mAb generated against β2-glycoprotein I significantly hindered AT inactivation of FIXa. More importantly, IgG from two positive plasma samples were found to interfere with AT inactivation of FIXa. In conclusion, IgG anti-FIXa Ab occurred in ∼30% of APS patients and could interfere with AT inactivation of FIXa. Because FIXa is an upstream procoagulant factor, impaired AT regulation of FIXa might contribute more toward thrombosis than the dysregulation of the downstream FXa and thrombin.
Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family
Authors: Abe Katsuaki , Endo Yuichi , Nakazawa Naomi , Kanno Kazuko , Okubo Mitsuo , Hoshino Tadashi , Fujita Teizo
Published: April 2014

A deficiency in the early components of complement is associated with an increased susceptibility to pyrogenic infections and multiple autoimmune diseases. We previously reported a Japanese case of selective C1s deficiency resulting from a compound heterozygosity for a 4-bp deletion in exon X and a nonsense mutation Glu597X in exon XII of the C1s gene. In this previous case, the patient suffered from unique symptoms including virus-associated hemophagocytic syndrome and died after a long period of loss of consciousness. In the present study, we report another patient from the same family, with C1s abnormality caused by a distinct compound-heterozygous genotype and who had a novel missense mutation Gly630Glu transmitted from the mother’s side and a previously identified nonsense mutation Glu597X from the father’s side. Thus three distinct mutations of the C1s gene were clustered and resulted in two distinct genotypes for C1s deficiency and C1s abnormality within this one family. The present patient showed symptoms that were similar in part to our previous patient, which were different from those of the cases reported in other families. The biochemical properties of C1s in the patient’s serum and the recombinant form were closely related to the undetectable or very low activity of complement activation. These results suggested that the uniqueness and severity of the symptoms observed here in the two patients might be under the control of a common C1s allele and distinct counterparts, respectively.
Phenotypic and Functional Analysis of CD4+CD25−Foxp3+ T Cells in Patients with Systemic Lupus Erythematosus
Authors: Bonelli Michael , Savitskaya Anastasia , Steiner Carl-Walter , Rath Eva , Smolen Josef S. , Scheinecker Clemens
Published: April 2014

CD4+CD25+Foxp3+ regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune diseases. Recent studies have described increased proportions of CD4+Foxp3+ T cells that lacked expression of CD25 in systemic lupus erythematosus (SLE) patients but the suppressive capacity of these cells has not been analyzed so far. We therefore performed combined phenotypic and functional analyses of CD4+CD25−Foxp3+ T cells in patients with autoimmune diseases and healthy controls (HC). Phenotypic analysis revealed increased proportions of CD4+CD25−Foxp3+ T cells in SLE patients as compared with patients with systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased proportions of CD4+CD25−Foxp3+ T cells correlated with the clinical disease activity and the daily cortisone dose. According to phenotypic analysis, CD4+CD25−Foxp3+ T cells resembled regulatory T cells rather than activated T cells. For functional analysis, a surrogate surface marker combination to substitute for intracellular Foxp3 was defined: CD4+CD25−CD127− T cells from SLE patients were isolated by FACS sorting and analyzed for their suppressive capacity in vitro. CD4+CD25−CD127− T cells, that contained up to 53% Foxp3+ T cells, were found to suppress T cell proliferation but not IFN-γ production in vitro. In summary, CD4+CD25−Foxp3+ T cells phenotypically and to a certain extent also functionally resemble conventional Treg. Despite increased proportions, however, their selective functional defects might contribute to the failure of Treg to control autoimmune dysregulation in SLE patients.
Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients
Authors: Peraldi Marie-Noëlle , Berrou Jeannig , Dulphy Nicolas , Seidowsky Alexandre , Haas Philippe , Boissel Nicolas , Metivier Fabien , Randoux Christine , Kossari Niloufar , Guérin Alain , Geffroy Sylvie , Delavaud Guy , Marin-Esteban Viviana , Glotz Denis , Charron Dominique , Toubert Antoine
Published: April 2014

To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.
Nicotinic Attenuation of Central Nervous System Inflammation and Autoimmunity
Authors: Shi Fu-Dong , Piao Wen-Hua , Kuo Yen-Ping , Campagnolo Denise I. , Vollmer Timothy L. , Lukas Ronald J.
Published: April 2014

The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c+ dendritic and CD11b+ infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.
Anti-Endothelial Antibodies Interfere in Apoptotic Cell Clearance and Promote Thrombosis in Patients with Antiphospholipid Syndrome
Authors: Graham Audrey , Ford Isobel , Morrison Rona , Barker Robert N. , Greaves Mike , Erwig Lars-Peter
Published: April 2014

Antiphospholipid syndrome is an important cause of recurrent thrombotic events. The pathogenesis of the thrombosis remains unclear, but it has been suggested that anti-phospholipid Abs, which are laboratory markers for the disease and include species capable of binding to vascular endothelial cells, play an important role. We hypothesized that these anti-endothelial Abs promote thrombosis through interference with clearance of dying cells. We show that healthy endothelial cell monolayers effectively remove apoptotic endothelial cells, but this clearance is markedly inhibited by serum or IgG from patients with antiphospholipid syndrome and anti-endothelial Abs. In addition, patient sera or IgG opsonize apoptotic endothelial cells and cause enhanced Fc-mediated uptake by professional phagocytes. Importantly, the delayed clearance of apoptotic cells by healthy endothelial cells and the enhanced Fc-mediated macrophage uptake each result in procoagulant consequences, as judged by increased thrombin generation. The effects on apoptotic cell clearance were reproduced by a mAb derived from a patient with antiphospholipid syndrome, which binds to endothelial cells and is thrombogenic in experimental models. Taken together, our data support a novel, dual mechanism by which anti-endothelial Abs are prothrombotic in antiphospholipid syndrome by inhibiting removal of procoagulant apoptotic cells and by diverting their clearance to provoke inflammatory and prothrombotic changes in professional phagocytes.
Eenheid in verscheidenheid - Het beeld van de letterkunde in Johan Huizinga’s Nederland’s beschaving in de zeventiende eeuw
Authors: Leuker Maria-Theresia
Published: April 2014

The following article focuses upon the image of seventeenth-century Dutch literature sketched by Johan Huizinga in his Holländische Kultur des siebzehnten Jahrhunderts (1933) and Nederland’s beschaving in de zeventiende eeuw (1941). The German version is based upon three lectures given by Huizinga in Cologne in 1932 and stresses the peculiarity of seventeenth-century Dutch culture. Despair of civilisation and the intention to stimulate his readers’ national pride determine the way in which he composes and presents ‘his’ literary canon in the 1941 Dutch version. This canon contains the familiar names: Vondel, Hooft, Huygens, Cats and Bredero. But nevertheless, Huizinga has his special manner to depict the poets and their works. On the one hand he emphasizes the differences between them, and on the other hand he shows how they complement one another. Altogether, they represent ‘eenheid in verscheidenheid’ (unity in diversity). To illustrate his view of seventeenth-century Dutch poets as a circle of friends, Huizinga uses the 19th-century myth of the Muiderkring, the circle of poets which P.C. Hooft was said to have gathered around him. Huizinga’s historiography aims at identification. Its intention is not only to impart knowledge, but also to convey experience. To achieve this, it visualizes the canon of seventeenth-century Dutch literature by painting a gallery of poets’ portraits.
Partikels volgens de schijf van vijf
Authors: Foolen Ad
Published: April 2014

Particles are a notorious problem for learners of Dutch as a foreign or second language. This paper focuses on the question of how courses for learners of Dutch deal with the Dutch particles (modal and other ones). One course, Help!, is analyzed in more detail. The findings are evaluated with the help of the so called ‘schijf van vijf’ (Westhoff 2008), a checklist which distinguishes five aspects: input, intake, focus on form, production, and strategies in language use. Whereas Help! provides a rich input of particles, the other aspects need closer attention in course development. Further descriptive and didactic research is necessary in order to implement a more effective way of teaching Dutch particles.
De literaire aspecten van de Costerlegende: Mythologie in de vorm van een klassieke pleitrede
Authors: Robbe Joost
Published: April 2014

This article presents an analysis of the rhetorical and stylistic methods adopted by Hadrian Junius (1511-1575) in the seventeenth chapter of his Batavia (1588), in which he aimed to argue that printing was invented by Laurens Janszoon Coster of Haarlem. The mythical status of the Coster Legend is, at present, uncontested and well documented, but Junius’ rhetorical argument, inspired by conversations with prominent citizens of Haarlem, has never before been subjected to such thorough analysis. This article makes it clear that Junius’ primary intention was not to convey facts, but to deliver a deliberate mythologisation of an already well-established legend about the invention of printing in Haarlem. He presented this mythologisation as a classical plea against the followers of Gutenberg.
‘Geesel Hollands’ of ‘Man onzer eeuw’? - Napoleon als splijtzwam in het Nederlandse literaire veld omstreeks 1840
Authors: Oosterholt Jan
Published: April 2014

The return of the relics of Napoleon to Paris (1840) gave rise to a critical debate in the Netherlands. In general the Dutch did approach the French veneration of Bonaparte in a skeptical way, although authors like Van der Hoop and Potgieter more or less sympathised with the French Napoleoncult. In this article the debate is analysed against the background of the relation between Dutch and French culture. Nationalistic, religious and cosmopolitan sentiments are interpreted in connection to the development of Pascale Casanova’s ‘world republic of letters’.
‘Van den Heer Grimm tot dankzegging voor zyne benoeming tot Correspondent’: bekende en nieuw ontdekte documenten voor de wetenschapsgeschiedenis
Authors: Schlusemann Rita
Published: April 2014

The relationship between Dutch and German philology as well as between Jacob and Wilhelm Grimm and the scientific institutions in the Low Countries have scarcely been a subject of research during the last few decades. However, the correspondence – known and recently found letters – between Jacob Grimm and the Dutch Institute of Science, Literature and the Fine Arts (the predecessor of the Royal Netherlands Academy of Science) shows that they held each other in great esteem. Especially the correspondence between Wil„lem Bilderdijk as the former secretary and Jacob Grimm was very friendly. Besides, because of his efforts for Dutch literature and language, Jacob Grimm even became the first foreign scholar the Institute appointed as an associate member in 1816. The article is intended as a step towards more research on the relationship between the two neighboring philologies in the nineteenth century.
U.S. CO2 Mitigation in a Global Context: Welfare, Trade and Land Use
Authors: Sands Ronald D. , Schumacher Katja , Forster Hannah
Published: April 2014

We describe carbon dioxide mitigation scenarios specified by the Energy Modeling Forum study (EMF-24) “U.S. Technology Transitions under Alternative Climate Policies,” using a global computable general equilibrium model that simulates world energy and agricultural systems through 2050. One set of scenarios covers variation across five major technology groups: end-use technology, carbon dioxide capture and storage, nuclear electricity generation, wind and solar power, and bioenergy. Other scenarios cover variation across policies. Policies such as a renewable portfolio standard for electricity generation or a clean electricity standard have the potential for significant emissions reductions, but at a greater cost than a cap-and-trade scenario with the same reduction in emissions. Cap-and-trade scenarios resulted in carbon dioxide leakage rates of 11 to 20 percent depending on the stringency of the targets. Oil-exporting regions without a mitigation policy may still have significant welfare losses when other world regions reduce emissions.
Assessing the Interactions among U.S. Climate Policy, Biomass Energy, and Agricultural Trade
Authors: Wise Marshall A. , McJeon Haewon C. , Calvin Katherine V. , Clarke Leon E. , Kyle Page
Published: April 2014

Energy from biomass is potentially an important contributor to U.S. climate change mitigation efforts. However, large-scale implementation of bioenergy competes with other uses of land, including agriculture and forest production and terrestrial carbon storage in non-commercial lands. And with trade, bioenergy could mean greater reliance on imported energy. Based on EMF-24 policy specifications, this paper explores these dimensions of bioenergy’s role in U.S. climate policy and the relationship to alternative measures for ameliorating the trade and land use consequences. It shows how widespread use of biomass in the U.S. could lead to imports; and it highlights that the relative stringency of domestic and international carbon mitigation policy will heavily influence the amount of imports. It demonstrates that limiting biomass imports could alter the balance of trade in other agricultural products. Finally, it shows that increasing efforts to protect both U.S. and international forests could also affect the balance of trade in other agricultural products.
A Two-stage Approach for Energy Efficiency Analysis in European Union Countries
Authors: Makridou Georgia , Andriosopoulos Kostas , Doumpos Michael , Zopounidis Constantin
Published: April 2014

This paper evaluates the energy efficiency of EU countries over the period 20002010. At the first stage, data envelopment analysis (DEA) is used, combining multiple energy consumption data and economic outputs. The efficiency estimates obtained from the analysis are evaluated in a second stage through a multiple criteria decision aiding methodology (MCDA). The proposed non-parametric approach combining DEA with MCDA enables modeling of the problem in an integrated manner, not only providing energy efficiency estimates but also supporting the analysis of the main contributing factors, as well as the development of a benchmarking model for energy efficiency evaluation at the country level.
Energy Price Reform and Household Welfare: The Case of Turkey
Authors: Zhang Fan
Published: April 2014

A price reform in Turkey increased the residential electricity tariff by more than 50 percent in 2008. The reform, aimed at encouraging energy efficiency and private investment, sparked considerable policy debate about its potential impact on household welfare. This paper estimates a short-run residential electricity demand function to evaluate the distributional impact of the tariff increase. The analysis allows heterogeneity in households’ price sensitivity and the model is estimated using a nationally representative sample of 8,572 Turkish households. The results suggest that rich households in Turkey are three times as responsive in adjusting consumption to price changes as poor households are. In addition, the welfare loss of the poorest income quintile—measured by the change in consumer surplus as a percentage of income—is 2.9 times that of the wealthiest.
Review on Some Malaysian Traditional Medicinal Plants with Therapeutic Properties
Authors: Ali Alsarhan  , Ahed Al-Khatib  , Naznin Sultana  , Mohammed Rafiq Abdul Kadir
Published: April 2014

There are many medicinal plants that have been used for thousands of years. These plants can now be found in herbal products and as part of the traditional Malaysian health care system because of their therapeutic efficacy. This paper discusses the use of ten medicinal plants in the traditional medicinal system of Malaysia and related scientific studies on their Pharmaceutical properties, which demonstrate their traditional uses. The plants viewed are Amaranthus spinosus L., Arundina graminifolia (D.Don) Hochr., Callicarpa arborea Roxb., Carica papaya L., Citrus grandis L., Coleus amboinicus Lour., Curcuma domestica Valeton., Psidium guajava L., Garcinia atroviridis Griff. ex T. Anders., and Zingiber officinale Rosc. All the plants mentioned in this paper have therapeutic properties, which explains and validates their uses in traditional medicine.
Insight on Interfacial Microstructure and Corrosion Characteristics of Mg/Al Explosive Welded Composite Plates
Authors: Lu Yuchen , Li Huizhong , Liang Xiaopeng , Chen Zhi , Zeng Zhiheng , Zhao Ming‐Chun , Atrens Andrej
Published: July 2024

Interfacial corrosion performance is crucial to the reliability of Mg/Al explosively welded composite plates. Nevertheless, more understanding is required concerning such interfacial corrosion. In this work, a combination of numerical simulation and experimental investigation was used to clarify the microstructure evolutions of AZ80‐Mg alloy/1060‐Al explosively welded composite plate. The formation of interfacial wave structure and the thermodynamic state were insighted through numerical simulation, which further enhanced the correlation between the interfacial microstructural heterogeneities and the interfacial corrosion characteristics. Galvanic corrosion was produced by the significant potential difference between the AZ80‐Mg and 1060‐Al, with multiple micro‐galvanic couples in the vortex zone. The corrosion occurred near the interface and gradually advanced away from the interface. After 1 h, the composite plates exhibited severe corrosion with deep pits on the Mg side, while the Al side was less affected. Within the vortex, however, the Mg‐rich region underwent little corrosion, whereas the Al‐rich region underwent significant corrosion, attributed to the increase in pH value caused by the Mg corrosion.
Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing
Authors: Gao Suyue , He Xuefeng , Liu Hengdeng , Liu Yiling , Wang Hanwen , Zhou Ziheng , Chen Lei , Ji Xiaoyuan , Yang Ronghua , Xie Julin
Published: July 2024

The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO₂–Au–mSiO₂@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO₂ head and MnO₂ extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO₂–Au–mSiO₂@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS‐scavenging and growth factor‐releasing system, is developed. The HAMA‐mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti‐inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.
Cross‐Species Prediction of Transcription Factor Binding by Adversarial Training of a Novel Nucleotide‐Level Deep Neural Network
Authors: Zhang Qinhu , Wang Siguo , Li Zhipeng , Pan Yijie , Huang De‐Shuang
Published: July 2024

Cross‐species prediction of TF binding remains a major challenge due to the rapid evolutionary turnover of individual TF binding sites, resulting in cross‐species predictive performance being consistently worse than within‐species performance. In this study, a novel Nucleotide‐Level Deep Neural Network (NLDNN) is first proposed to predict TF binding within or across species. NLDNN regards the task of TF binding prediction as a nucleotide‐level regression task, which takes DNA sequences as input and directly predicts experimental coverage values. Beyond predictive performance, it also assesses model performance by locating potential TF binding regions, discriminating TF‐specific single‐nucleotide polymorphisms (SNPs), and identifying causal disease‐associated SNPs. The experimental results show that NLDNN outperforms the competing methods in these tasks. Then, a dual‐path framework is designed for adversarial training of NLDNN to further improve the cross‐species prediction performance by pulling the domain space of human and mouse species closer. Through comparison and analysis, it finds that adversarial training not only can improve the cross‐species prediction performance between humans and mice but also enhance the ability to locate TF binding regions and discriminate TF‐specific SNPs. By visualizing the predictions, it is figured out that the framework corrects some mispredictions by amplifying the coverage values of incorrectly predicted peaks.
TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2‐CaMK4‐CREB Feedback Loop Activation
Authors: Song In‐Sung , Jeong Yu‐Jeong , Yun Jae Kwang , Lee Jimin , Yang Hae‐Jun , Park Young‐Ho , Kim Sun‐Uk , Hong Seung‐Mo , Lee Peter C.W. , Lee Geun Dong , Jang Sung‐Wuk
Published: July 2024

Frequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator‐Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin‐dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2‐mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element‐binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib‐induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2‐CaMK4‐CREB axis as a driving force and upregulates the expression of stemness‐ and survival‐related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.
Evaluation of preoperative visceral fat area / psoas muscle area ratio and prognosis in patients with colorectal cancer
Authors: Hosoi Nobuhiro , Shiraishi Takuya , Okada Takuhisa , Osone Katsuya , Yokobori Takehiko , Sakai Makoto , Ogawa Hiroomi , Sohda Makoto , Shirabe Ken , Saeki Hiroshi
Published: July 2024

Background

Recent research has focused on the prognostic relevance of preoperative sarcopenia and sarcopenic obesity in various cancers. In this study we investigated the relationship between visceral fat area (VFA), psoas muscle area (PMA), and the prognosis of patients undergoing colorectal cancer surgery.

Methods

Patients with stage III colorectal cancer who underwent surgery between July 2013 and April 2020 were included. The analysis was performed on 151 patients who met the criteria. The VFA and PMA were measured at the level of the third lumbar vertebra on computed tomography (CT) scans, and the ratio of VFA to PMA (V/P ratio) was determined.

Results

Patients with high V/P ratios were significantly older (p = 0.0213), had a higher body mass index (BMI) (p < 0.0001), a higher percentage of sarcopenic obesity (p < 0.0001), and more diabetes complications (p < 0.0001). Prognostic analysis showed that the overall survival (OS) (p = 0.0154) and relapse‐free survival (RFS) (p = 0.0378) were significantly worse in patients with a high V/P ratio. Multivariate analysis revealed that a high V/P ratio was an independent poor prognostic factor for OS. Subgroup analysis was then performed in patients with BMI < 25 kg/m2. OS (p = 0.0259) and RFS (p = 0.0275) were significantly worse in the high V/P ratio group. A high V/P ratio was an independent poor prognostic factor in the multivariate analysis.

Conclusion

In colorectal cancer, the preoperative V/P ratio is an independent factor for poor prognosis. Preoperative evaluation of the V/P ratio may identify a wide range of high‐risk patients because it is an independent poor prognostic factor in patients without obesity.
Naturally Occurring Plant‐Based Anticancerous Candidates as Potential ERK2 Inhibitors: In‐Silico Database Mining and Molecular Dynamics Simulations
Authors: Ibrahim Mahmoud A. A. , Ali Sara S. M. , Abdelrahman Alaa H. M. , Abdeljawaad Khlood A. A. , Sidhom Peter A. , Sayed Shaban R. M. , El‐Tayeb Mohamed A. , Paré Paul W. , Hegazy Mohamed‐Elamir F.
Published: July 2024

The evolutionarily conserved extracellular signal‐regulated kinase 2 (ERK2) is involved in regulating cellular signaling in both normal and pathological conditions. ERK2 expression is critical for human development, while hyperactivation is a major factor in tumor progression. Up to now, there have been no approved inhibitors that target ERK2, and as such, here we report on screening of a naturally occurring plant‐based anticancerous compound‐activity‐target (NPACT) database for prospective ERK2 inhibitors. More than 1,500 phytochemicals were screened using in‐silico molecular docking and molecular dynamics (MD) approaches. NPACT compounds with a docking score lower than a co‐crystallized LHZ inhibitor (calc. −10.5 kcal/mol) were subjected to MD simulations. Binding energies (ΔGbinding) of inhibitor‐ERK2 complexes over the MD course were estimated using an MM‐GBSA approach. Based on MM‐GBSA//100 ns MD simulations, the steroid zhankuic acid C (NPACT01034) demonstrated greater binding affinity against ERK2 protein than LHZ, with ΔGbinding values of −50.0 and −47.7 kcal/mol, respectively. Structural and energetical analyses throughout the MD course demonstrated stabilization of zhankuic acid C complexed with ERK2 protein. The anticipated ADMET properties of zhankuic acid C indicated minimal toxicity. Moreover, in‐silico evaluation of fourteen ERK2 inhibitors in clinical trials demonstrated the higher binding affinity of zhankuic acid C towards ERK2 protein.
Seven New Noroleanane Triterpenoids from Mastic and Their NO Inhibitory and Cytotoxic Activities
Authors: An Xue‐rui , Wang Jun‐long , Sun Yu‐wei , Yang Xin , Wu Yan , Liu Wei , Yuan Tao
Published: July 2024

Mastic is a natural resin produced by Pistacia lentiscus L. (Anacardiaceae) with high medicinal value and have been traditionally used as Uighur imported medicine for centuries. In this study, 16 triterpenoids including seven new noroleanane triterpenoids (1–7), along with nine known oleanane triterpenoids (8–16), were isolated from the mastic. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, UV, ESI‐HR‐MS and NMR spectroscopy) and singlecrystal X‐ray diffraction. Compounds 4–7, 11, 14 and 16 showed strong inhibitory NO production in LPS‐induced RAW264.7 cells with IC50 values 7.44–9.76 μM, respectively (positive control dexamethasone, 9.93±1.17 μM). Furthermore, compounds 3 and 12 significantly inhibited the growth of SW480 cells, compound 3 showed the most pronounced inhibitory effect with an IC50 of 2.30±0.38 μM.
Overview of the Mechanism of Degradation of Pharmaceuticals by Persulfate/Peroxysulfate Catalysts
Authors: Anjorin Excel O. , Alfred Moses O. , Sotunde Babajide , Nnamani Esther A. , Bayode Ajibola A. , Unuabonah Emmanuel I. , Helmreich Brigitte , Omorogie Martins O.
Published: July 2024

The leaching of pharmaceutical ingredients into water bodies poses an escalating threat, demanding urgent remediation strategies. Among several techniques advanced for their remediation, advanced oxidation methods utilizing persulfate (PS) and peroxymonosulfate (PMS) stand out as promising avenues for pharmaceutical degradation in wastewater. This article consolidates the research on photocatalytic degradation of pharmaceutical contaminants, focusing on PMS‐based photoactive composites, and elucidates their efficacy in removing active pharmaceutical ingredients from water. Moreover, it delineates alternative techniques for activating PS and PMS, providing a holistic understanding of the field's advancements. By outlining research limitations and knowledge gaps, this review underscores the imperative for further investigation and innovation in pharmaceutical wastewater treatment.
Tinea capitis (Favus) in a 8‐year‐old child: Case report
Authors: Akbari Negarin , Parhiz Jabbar , Sabzi Zahra
Published: July 2024

Key Clinical Message

In examining any scalp itch or skin lesions, especially in children with long hair, fungal lesions under the hair may not be diagnosed in a timely manner. Additionally, fungal infection of the scalp, known as tinea capitis, is considered a chronic condition and if left untreated, it can lead to alopecia (hair loss) and permanent scarring.

Tinea capitis (TC) is a common cutaneous fungal infection in childhood. In this report, we describe the case of an 8‐year‐old child presenting with erythematous scalp lesions accompanied by hair loss. Upon examination, palpation revealed a swollen and tender left parotid gland. Notably, the frontal region of the scalp exhibited erythematous lesions and scaly red plaques resembling yellowish paste‐like dough. Subsequent clinical evaluation and culture analysis confirmed the diagnosis of TC. The patient received treatment with Terbinafine 125 mg for a duration of 8 weeks. Follow‐up examinations conducted after 3 months showed no signs of recurrence. Accurate diagnosis and timely treatment, along with adherence to medication regimens, are crucial in cases of TC, and differential diagnoses should be considered. Treatment should commence promptly upon diagnosis to prevent complications such as scalp baldness and transmission to others. This case report underscores the significance of establishing a precise diagnosis and effective treatment for this dermatophytosis to mitigate the risk of recurrences or therapeutic shortcomings, particularly in infants.