scholarly journals A Novel Role of IGF1 in Apo2L/TRAIL-Mediated Apoptosis of Ewing Tumor Cells

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Frans van Valen ◽  
Henning Harrer ◽  
Marc Hotfilder ◽  
Uta Dirksen ◽  
Thomas Pap ◽  
...  
Keyword(s):  
De Novo ◽  
Fumonisin B1 ◽  
Chemotherapeutic Agents ◽  
Ceramide Synthase ◽  
Short Term ◽  
Igf1 Receptor ◽  
Induced Apoptosis ◽  
Survival Effect

Insulin-like growth factor 1 (IGF1) reputedly opposes chemotoxicity in Ewing sarcoma family of tumor (ESFT) cells. However, the effect of IGF1 on apoptosis induced by apoptosis ligand 2 (Apo2L)/tumor necrosis factor (TNF-) related apoptosis-inducing ligand (TRAIL) remains to be established. We find that opposite to the partial survival effect of short-term IGF1 treatment, long-term IGF1 treatment amplified Apo2L/TRAIL-induced apoptosis in Apo2L/TRAIL-sensitive but not resistant ESFT cell lines. Remarkably, the specific IGF1 receptor (IGF1R) antibodyα-IR3 was functionally equivalent to IGF1. Short-term IGF1 incubation of cells stimulated survival kinase AKT and increased X-linked inhibitor of apoptosis (XIAP) protein which was associated with Apo2L/TRAIL resistance. In contrast, long-term IGF1 incubation resulted in repression of XIAP protein through ceramide (Cer) formation derived from de novo synthesis which was associated with Apo2L/TRAIL sensitization. Addition of ceramide synthase (CerS) inhibitor fumonisin B1 during long-term IGF1 treatment reduced XIAP repression and Apo2L/TRAIL-induced apoptosis. Noteworthy, the resistance to conventional chemotherapeutic agents was maintained in cells following chronic IGF1 treatment. Overall, the results suggest that chronic IGF1 treatment renders ESFT cells susceptible to Apo2L/TRAIL-induced apoptosis and may have important implications for the biology as well as the clinical management of refractory ESFT.

scholarly journals Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicity-induced apoptosis of INS-1 β-cells

2011 ◽  
Vol 438 (1) ◽  
pp. 177-189 ◽  
Author(s):  
Julien Véret ◽  
Nicolas Coant ◽  
Evgeny V. Berdyshev ◽  
Anastasia Skobeleva ◽  
Nicole Therville ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
De Novo ◽  
Acyl Chain ◽  
Fumonisin B1 ◽  
Ceramide Synthase ◽  
Β Cells ◽  
Β Cell ◽  
Induced Apoptosis ◽  
Synthase Inhibitor ◽  
Chain Lengths

Pancreatic β-cell apoptosis induced by palmitate requires high glucose concentrations. Ceramides have been suggested to be important mediators of glucolipotoxicity-induced β-cell apoptosis. In INS-1 β-cells, 0.4 mM palmitate with 5 mM glucose increased the levels of dihydrosphingosine and dihydroceramides, two lipid intermediates in the de novo biosynthesis of ceramides, without inducing apoptosis. Increasing glucose concentrations to 30 mM amplified palmitate-induced accumulation of dihydrosphingosine and the formation of (dihydro)ceramides. Of note, glucolipotoxicity specifically induced the formation of C18:0, C22:0 and C24:1 (dihydro)ceramide molecular species, which was associated with the up-regulation of CerS4 (ceramide synthase 4) levels. Fumonisin-B1, a ceramide synthase inhibitor, partially blocked apoptosis induced by glucolipotoxicity. In contrast, apoptosis was potentiated in the presence of D,L-threo-1-phenyl-2-palmitoylamino-3-morpholinopropan-1-ol, an inhibitor of glucosylceramide synthase. Moreover, overexpression of CerS4 amplified ceramide production and apoptosis induced by palmitate with 30 mM glucose, whereas down-regulation of CerS4 by siRNA (short interfering RNA) reduced apoptosis. CerS4 also potentiates ceramide accumulation and apoptosis induced by another saturated fatty acid: stearate. Collectively, our results suggest that glucolipotoxicity induces β-cell apoptosis through a dual mechanism involving de novo ceramide biosynthesis and the formation of ceramides with specific N-acyl chain lengths rather than an overall increase in ceramide content.

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide

2012 ◽  
Vol 302 (1) ◽  
pp. H319-H332 ◽  
Author(s):  
Burton M. Altura ◽  
Nilank C. Shah ◽  
Gatha Shah ◽  
Aimin Zhang ◽  
Wenyan Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
De Novo ◽  
Magnesium Deficiency ◽  
Smooth Muscles ◽  
Fumonisin B1 ◽  
Left Ventricular ◽  
Ceramide Synthase ◽  
Short Term ◽  
Aortic Smooth Muscle ◽  
Cytokines And Chemokines

The present study tested the hypotheses that 1) short-term dietary deficiency (MgD) of magnesium (21 days) would result in the upregulation of ceramide synthase (CS) in left ventricular (LV), right ventricular, atrial, and aortic smooth muscle, as well as induce a synthesis/release of select cytokines and chemokines into the LV and aortic smooth muscle and serum; 2) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg concentration would lead to the synthesis/release of select cytokines/chemokines, activation of N-SMase, and the de novo synthesis of ceramide; and 3) inhibition of CS by fumonisin B1 (FB1) or inhibition of neutral sphingomyelinase (N-SMase) by scyphostatin (SCY) in VSMCs exposed to low Mg would result in reductions in the levels of the cytokines/chemokines and lowered levels of ceramide concomitant with inhibition of NF-κB activation. The data indicated that short-term MgD (10% normal dietary intake) resulted in the upregulation of CS in ventricular, atrial, and aortic smooth muscles coupled to the synthesis/release of 12 different cytokines/chemokines, as well as activation of NF-κB in the LV and aortic smooth muscle and sera; even very low levels of water-borne Mg (e.g., 15 mg·l−1·day−1) either prevented or ameliorated the upregulation and synthesis of the cytokines/chemokines. Our experiments also showed that VSMCs exposed to low extracellular Mg resulted in the synthesis of 5 different cytokines and chemokines concomitant with synthesis/release of ceramide. However, inhibition of the synthesis and release of ceramide by either FB1 or SCY attenuated, markedly , the generation of ceramide, release of the cytokines/chemokines, and activation of NF-κB (as measured by activated p65 and cRel).

Impact of FII’s and FDI’s on Indian Stock Market

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Dr. Kamlesh Kumar Shukla
Keyword(s):  
Stock Market ◽  
Financial Markets ◽  
Global Economy ◽  
Short Term ◽  
Earnings Growth ◽  
The Past ◽  
Bull Market ◽  
Indian Stock Market

FIIs are companies registered outside India. In the past four years there has been more than $41 trillion worth of FII funds invested in India. This has been one of the major reasons on the bull market witnessing unprecedented growth with the BSE Sensex rising 221% in absolute terms in this span. The present downfall of the market too is influenced as these FIIs are taking out some of their invested money. Though there is a lot of value in this market and fundamentally there is a lot of upside in it. For long-term value investors, there’s little because for worry but short term traders are adversely getting affected by the role of FIIs are playing at the present. Investors should not panic and should remain invested in sectors where underlying earnings growth has little to do with financial markets or global economy.

Introduction: Kinship Bereavement in Later Life

1997 ◽  
Vol 35 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Brian De Vries
Keyword(s):  
Adult Child ◽  
Later Life ◽  
Short Term ◽  
Traumatic Grief ◽  
Death Of A Parent ◽  
De Vries ◽  
Longitudinal Effects ◽  
Analysis Of Variation

This article introduces a volume devoted to the examination of later-life bereavement: an analysis of variation in cause, course, and consequence. Six articles address and represent this variation and comprise this volume: 1) Prigerson et al. present case histories of the traumatic grief of spouses; 2) Hays et al. highlight the bereavement experiences of siblings in contrast to those spouses and friends; 3) Moss et al. address the role of gender in middle-aged children's responses to parent death; 4) Bower focuses on the language adopted by these adult children in accepting the death of a parent; 5) de Vries et al. explore the long-term, longitudinal effects on the psychological and somatic functioning of parents following the death of an adult child; and 6) Fry presents the short-term and longitudinal reactions of grandparents to the death of a grandchild. A concluding article is offered by de Vries stressing both the unique and common features of these varied bereavement experiences touching on some of the empirical issues and suggesting potential implications and applications.

scholarly journals Shades between Black and Green Investment: Balance or Imbalance?

2021 ◽  
Vol 13 (9) ◽  
pp. 5024
Author(s):  
 Vítor Manuel de Sousa Gabriel ◽  
María Mar Miralles-Quirós ◽  
José Luis Miralles-Quirós
Keyword(s):  
Risk Factor ◽  
Oil Prices ◽  
Oil Price ◽  
Short Term ◽  
Environmental Indices ◽  
Long Run ◽  
Green Investment ◽  
Bounds Test

This paper analyses the links established between environmental indices and the oil price adopting a double perspective, long-term and short-term relationships. For that purpose, we employ the Bounds Test and bivariate conditional heteroscedasticity models. In the long run, the pattern of behaviour of environmental indices clearly differed from that of the oil prices, and it was not possible to identify cointegrating vectors. In the short-term, it was possible to conclude that, in contemporaneous terms, the variables studied tended to follow similar paths. When the lag of the oil price variable was considered, the impacts produced on the stock market sectors were partially of a negative nature, which allows us to suppose that this variable plays the role of a risk factor for environmental investment.

scholarly journals The key role of contact time in elucidating the mechanisms of enhanced decontamination by Fe0/MnO2/sand systems

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Viet Cao ◽  
Ghinwa Alyoussef ◽  
Nadège Gatcha-Bandjun ◽  
Willis Gwenzi ◽  
Chicgoua Noubactep
Keyword(s):  
Contact Time ◽  
Diffusive Transport ◽  
Iron Hydroxides ◽  
Iron Corrosion ◽  
Short Term ◽  
Batch Studies ◽  
Water Decontamination ◽  
Co Precipitation

AbstractMetallic iron (Fe0) has shown outstanding performances for water decontamination and its efficiency has been improved by the presence of sand (Fe0/sand) and manganese oxide (Fe0/MnOx). In this study, a ternary Fe0/MnOx/sand system is characterized for its discoloration efficiency of methylene blue (MB) in quiescent batch studies for 7, 18, 25 and 47 days. The objective was to understand the fundamental mechanisms of water treatment in Fe0/H2O systems using MB as an operational tracer of reactivity. The premise was that, in the short term, both MnO2 and sand delay MB discoloration by avoiding the availability of free iron corrosion products (FeCPs). Results clearly demonstrate no monotonous increase in MB discoloration with increasing contact time. As a rule, the extent of MB discoloration is influenced by the diffusive transport of MB from the solution to the aggregates at the bottom of the vessels (test-tubes). The presence of MnOx and sand enabled the long-term generation of iron hydroxides for MB discoloration by adsorption and co-precipitation. Results clearly reveal the complexity of the Fe0/MnOx/sand system, while establishing that both MnOx and sand improve the efficiency of Fe0/H2O systems in the long-term. This study establishes the mechanisms of the promotion of water decontamination by amending Fe0-based systems with reactive MnOx.

scholarly journals Reform in the international food aid regime: the role of consensual knowledge

1992 ◽  
Vol 46 (1) ◽  
pp. 225-264 ◽  
Author(s):  
Raymond F. Hopkins
Keyword(s):  
Economic Development ◽  
International Organizations ◽  
Epistemic Community ◽  
Food Aid ◽  
Local Production ◽  
Short Term ◽  
The 1950S ◽  
Food Imports

The principles and norms adopted by the regime governing food aid in the 1950s have changed substantially during the subsequent three decades. Explaining the changes necessarily includes analyzing the efforts of an international epistemic community consisting of economic development specialists, agricultural economists, and administrators of food aid. According to the initial regime principles, food aid should be provided from donors' own surplus stocks, should supplement the usual commercial food imports in recipient countries, should be given under short-term commitments sensitive to the political and economic goals of donors, and should directly feed hungry people. As a result of following these principles, the epistemic community and other critics argued, food aid often had the adverse effects of reducing local production of food in recipient countries and exacerbating rather than alleviating hunger. The epistemic community (1) developed and proposed ideas for more efficiently supplying food aid and avoiding “disincentive” effects and (2) pushed for reforms to make food aid serve as the basis for the recipients' economic development and to target it at addressing long-term food security problems. The ideas of the international epistemic community have increasingly received support from international organizations and the governments of donor and recipient nations. Most recently, they have led to revisions of the U.S. food aid program passed by Congress in October 1990 and signed into law two months later. As the analysis of food aid reform demonstrates, changes in the international regime have been incremental, rather than radical. Moreover, the locus for the change has shifted from an American-centered one in the 1950s to a more international one in recent decades.

Economic valuation and the commodification of ecosystem services

2011 ◽  
Vol 35 (5) ◽  
pp. 613-628 ◽  
Author(s):  
Erik Gómez-Baggethun ◽  
Manuel Ruiz-Pérez
Keyword(s):  
Ecosystem Services ◽  
Environmental Policy ◽  
Biodiversity Conservation ◽  
Economic Valuation ◽  
Short Term ◽  
Valuation Of Ecosystem Services ◽  
Equity Of Access ◽  
The Way

In the last decade a growing number of environmental scientists have advocated economic valuation of ecosystem services as a pragmatic short-term strategy to communicate the value of biodiversity in a language that reflects dominant political and economic views. This paper revisits the controversy on economic valuation of ecosystem services in the light of two aspects that are often neglected in ongoing debates. First, the role of the particular institutional setup in which environmental policy and governance is currently embedded in shaping valuation outcomes. Second, the broader economic and sociopolitical processes that have governed the expansion of pricing into previously non-marketed areas of the environment. Our analysis suggests that within the institutional setup and broader sociopolitical processes that have become prominent since the late 1980s economic valuation is likely to pave the way for the commodification of ecosystem services with potentially counterproductive effects in the long term for biodiversity conservation and equity of access to ecosystem services benefits.

scholarly journals Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

Circulation ◽  
1993 ◽  
Vol 88 (3) ◽  
pp. 1205-1214 ◽  
Author(s):  
P Golino ◽  
G Ambrosio ◽  
M Ragni ◽  
I Pascucci ◽  
M Triggiani ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activating Factor ◽  
Short Term

Labor lawsuits and debt maturity

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Omer Unsal
Keyword(s):  
Chief Executive ◽  
Debt Maturity ◽  
Employee Relations ◽  
Short Term ◽  
Content Type ◽  
Negative Effect ◽  
Debt Market ◽  
Legal Fees

Purpose This paper aims to investigate how firms’ relationships with employees define their debt maturity. The authors empirically test the role of employee litigations in influencing firms’ choice of short-term versus long-term debt. The authors study employee relations by analyzing the importance of the workplace environment on capital structure. Design/methodology/approach The author’s test hypotheses using a sample of US publicly traded firms between 2000 and 2017, including 3,056 unique firms with 4,256 unique chief executive officer, adopting the fixed effect panel model. Findings The authors document that employee litigations have a significant negative effect on the use of short-term debt and a significant positive affect on long-term debt. Employee litigations, along with legal fees, outcomes and charging parties, matter the most in explaining debt maturity. In addition, frequently sued firms abandon the short-term debt market and use less shareholders’ equity to finance their operations while relying more on the longer debt market. Originality/value To the best of the authors’ knowledge, this is the first study to examine the role of employee mistreatment in debt maturity choice. The study extends the lawsuit and finance literature by examining unique, hand-collected data sets of employee lawsuits, allegations, violations, settlements, charging parties, case outcomes and case durations.

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