7 CFR 1484.54 - What expenditures may FAS reimburse under the Cooperator program?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false What expenditures may FAS reimburse under the... may FAS reimburse under the Cooperator program? (a) A Cooperator may seek reimbursement for an... source. (b) Subject to paragraph (a) of this section, FAS will reimburse, in whole or in part, the cost...

7 CFR 1484.30 - How does FAS formalize its working relationship with approved Cooperators?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false How does FAS formalize its working relationship with... FAS formalize its working relationship with approved Cooperators? FAS will notify each applicant in... sign the program agreement and submit the signed agreement to the Director, Marketing Operations Staff...

Nucleolin inhibits Fas ligand binding and suppresses Fas-mediated apoptosis in vivo via a surface nucleolin-Fas complex.

PubMed

Wise, Jillian F; Berkova, Zuzana; Mathur, Rohit; Zhu, Haifeng; Braun, Frank K; Tao, Rong-Hua; Sabichi, Anita L; Ao, Xue; Maeng, Hoyoung; Samaniego, Felipe

2013-06-06

Resistance to Fas-mediated apoptosis is associated with poor cancer outcomes and chemoresistance. To elucidate potential mechanisms of defective Fas signaling, we screened primary lymphoma cell extracts for Fas-associated proteins that would have the potential to regulate Fas signaling. An activation-resistant Fas complex selectively included nucleolin. We confirmed the presence of nucleolin-Fas complexes in B-cell lymphoma cells and primary tissues, and the absence of such complexes in B-lymphocytes from healthy donors. RNA-binding domain 4 and the glycine/arginine-rich domain of nucleolin were essential for its association with Fas. Nucleolin colocalized with Fas on the surface of B-cell lymphoma cells. Nucleolin knockdown sensitized BJAB cells to Fas ligand (FasL)-induced and Fas agonistic antibody-induced apoptosis through enhanced binding, suggesting that nucleolin blocks the FasL-Fas interaction. Mice transfected with nucleolin were protected from the lethal effects of agonistic anti-mouse Fas antibody (Jo2) and had lower rates of hepatocyte apoptosis, compared with vector and a non-Fas-binding mutant of nucleolin. Our results show that cell surface nucleolin binds Fas, inhibits ligand binding, and thus prevents induction of Fas-mediated apoptosis in B-cell lymphomas and may serve as a new therapeutic target.

Nucleolin inhibits Fas ligand binding and suppresses Fas-mediated apoptosis in vivo via a surface nucleolin-Fas complex

PubMed Central

Wise, Jillian F.; Berkova, Zuzana; Mathur, Rohit; Zhu, Haifeng; Braun, Frank K.; Tao, Rong-Hua; Sabichi, Anita L.; Ao, Xue; Maeng, Hoyoung

2013-01-01

Resistance to Fas-mediated apoptosis is associated with poor cancer outcomes and chemoresistance. To elucidate potential mechanisms of defective Fas signaling, we screened primary lymphoma cell extracts for Fas-associated proteins that would have the potential to regulate Fas signaling. An activation-resistant Fas complex selectively included nucleolin. We confirmed the presence of nucleolin-Fas complexes in B-cell lymphoma cells and primary tissues, and the absence of such complexes in B-lymphocytes from healthy donors. RNA-binding domain 4 and the glycine/arginine-rich domain of nucleolin were essential for its association with Fas. Nucleolin colocalized with Fas on the surface of B-cell lymphoma cells. Nucleolin knockdown sensitized BJAB cells to Fas ligand (FasL)-induced and Fas agonistic antibody-induced apoptosis through enhanced binding, suggesting that nucleolin blocks the FasL–Fas interaction. Mice transfected with nucleolin were protected from the lethal effects of agonistic anti-mouse Fas antibody (Jo2) and had lower rates of hepatocyte apoptosis, compared with vector and a non-Fas-binding mutant of nucleolin. Our results show that cell surface nucleolin binds Fas, inhibits ligand binding, and thus prevents induction of Fas-mediated apoptosis in B-cell lymphomas and may serve as a new therapeutic target. PMID:23599269

Integrating NASA Earth Science Enterprise (ESE) Data Into Global Agricultural Decision Support Systems

NASA Astrophysics Data System (ADS)

Teng, W.; Kempler, S.; Chiu, L.; Doraiswamy, P.; Liu, Z.; Milich, L.; Tetrault, R.

2003-12-01

Monitoring global agricultural crop conditions during the growing season and estimating potential seasonal production are critically important for market development of U.S. agricultural products and for global food security. Two major operational users of satellite remote sensing for global crop monitoring are the USDA Foreign Agricultural Service (FAS) and the U.N. World Food Programme (WFP). The primary goal of FAS is to improve foreign market access for U.S. agricultural products. The WFP uses food to meet emergency needs and to support economic and social development. Both use global agricultural decision support systems that can integrate and synthesize a variety of data sources to provide accurate and timely information on global crop conditions. The Goddard Space Flight Center Earth Sciences Distributed Active Archive Center (GES DAAC) has begun a project to provide operational solutions to FAS and WFP, by fully leveraging results from previous work, as well as from existing capabilities of the users. The GES DAAC has effectively used its recently developed prototype TRMM Online Visualization and Analysis System (TOVAS) to provide ESE data and information to the WFP for its agricultural drought monitoring efforts. This prototype system will be evolved into an Agricultural Information System (AIS), which will operationally provide ESE and other data products (e.g., rainfall, land productivity) and services, to be integrated into and thus enhance the existing GIS-based, decision support systems of FAS and WFP. Agriculture-oriented, ESE data products (e.g., MODIS-based, crop condition assessment product; TRMM derived, drought index product) will be input to a crop growth model in collaboration with the USDA Agricultural Research Service, to generate crop condition and yield prediction maps. The AIS will have the capability for remotely accessing distributed data, by being compliant with community-based interoperability standards, enabling easy access to

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance.

PubMed

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL.

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance

PubMed Central

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL. PMID:28424702

USDA Foreign Agricultural Service overview for operational monitoring of current crop conditions and production forecasts.

NASA Astrophysics Data System (ADS)

Crutchfield, J.

2016-12-01

The presentation will discuss the current status of the International Production Assessment Division of the USDA ForeignAgricultural Service for operational monitoring and forecasting of current crop conditions, and anticipated productionchanges to produce monthly, multi-source consensus reports on global crop conditions including the use of Earthobservations (EO) from satellite and in situ sources.United States Department of Agriculture (USDA) Foreign Agricultural Service (FAS) International Production AssessmentDivision (IPAD) deals exclusively with global crop production forecasting and agricultural analysis in support of the USDAWorld Agricultural Outlook Board (WAOB) lockup process and contributions to the World Agricultural Supply DemandEstimates (WASE) report. Analysts are responsible for discrete regions or countries and conduct in-depth long-termresearch into national agricultural statistics, farming systems, climatic, environmental, and economic factors affectingcrop production. IPAD analysts become highly valued cross-commodity specialists over time, and are routinely soughtout for specialized analyses to support governmental studies. IPAD is responsible for grain, oilseed, and cotton analysison a global basis. IPAD is unique in the tools it uses to analyze crop conditions around the world, including customweather analysis software and databases, satellite imagery and value-added image interpretation products. It alsoincorporates all traditional agricultural intelligence resources into its forecasting program, to make the fullest use ofavailable information in its operational commodity forecasts and analysis. International travel and training play animportant role in learning about foreign agricultural production systems and in developing analyst knowledge andcapabilities.

Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

PubMed

Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn

2010-04-01

The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.

Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability

PubMed Central

Rossin, A; Durivault, J; Chakhtoura-Feghali, T; Lounnas, N; Gagnoux-Palacios, L; Hueber, A-O

2015-01-01

The death receptor Fas undergoes a variety of post-translational modifications including S-palmitoylation. This protein acylation has been reported essential for an optimal cell death signaling by allowing both a proper Fas localization in cholesterol and sphingolipid-enriched membrane nanodomains, as well as Fas high-molecular weight complexes. In human, S-palmitoylation is controlled by 23 members of the DHHC family through their palmitoyl acyltransferase activity. In order to better understand the role of this post-translational modification in the regulation of the Fas-mediated apoptosis pathway, we performed a screen that allowed the identification of DHHC7 as a Fas-palmitoylating enzyme. Indeed, modifying DHHC7 expression by specific silencing or overexpression, respectively, reduces or enhances Fas palmitoylation and DHHC7 co-immunoprecipitates with Fas. At a functional level, DHHC7-mediated palmitoylation of Fas allows a proper Fas expression level by preventing its degradation through the lysosomes. Indeed, the decrease of Fas expression obtained upon loss of Fas palmitoylation can be restored by inhibiting the lysosomal degradation pathway. We describe the modification of Fas by palmitoylation as a novel mechanism for the regulation of Fas expression through its ability to circumvent its degradation by lysosomal proteolysis. PMID:25301068

Impairment of Fas-ligand-caveolin-1 interaction inhibits Fas-ligand translocation to rafts and Fas-ligand-induced cell death.

PubMed

Glukhova, Xenia A; Trizna, Julia A; Proussakova, Olga V; Gogvadze, Vladimir; Beletsky, Igor P

2018-01-22

Fas-ligand/CD178 belongs to the TNF family proteins and can induce apoptosis through death receptor Fas/CD95. The important requirement for Fas-ligand-dependent cell death induction is its localization to rafts, cholesterol- and sphingolipid-enriched micro-domains of membrane, involved in regulation of different signaling complexes. Here, we demonstrate that Fas-ligand physically associates with caveolin-1, the main protein component of rafts. Experiments with cells overexpressing Fas-ligand revealed a FasL N-terminal pre-prolin-rich region, which is essential for the association with caveolin-1. We found that the N-terminal domain of Fas-ligand bears two caveolin-binding sites. The first caveolin-binding site binds the N-terminal domain of caveolin-1, whereas the second one appears to interact with the C-terminal domain of caveolin-1. The deletion of both caveolin-binding sites in Fas-ligand impairs its distribution between cellular membranes, and attenuates a Fas-ligand-induced cytotoxicity. These results demonstrate that the interaction of Fas-ligand and caveolin-1 represents a molecular basis for Fas-ligand translocation to rafts, and the subsequent induction of Fas-ligand-dependent cell death. A possibility of a similar association between other TNF family members and caveolin-1 is discussed.

7 CFR 1484.21 - How does FAS determine which Cooperator program applications are approved?

Code of Federal Regulations, 2013 CFR

2013-01-01

... FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Application and Fund Allocation § 1484.21 How does FAS... that effectively supports the strategic decision-making initiatives of the Government Performance and... creation, expansion, or maintenance of foreign markets, FAS seeks to identify those projects that would...

7 CFR 1484.21 - How does FAS determine which Cooperator program applications are approved?

Code of Federal Regulations, 2012 CFR

2012-01-01

... FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Application and Fund Allocation § 1484.21 How does FAS... that effectively supports the strategic decision-making initiatives of the Government Performance and... creation, expansion, or maintenance of foreign markets, FAS seeks to identify those projects that would...

7 CFR 1484.21 - How does FAS determine which Cooperator program applications are approved?

Code of Federal Regulations, 2014 CFR

2014-01-01

... FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Application and Fund Allocation § 1484.21 How does FAS... that effectively supports the strategic decision-making initiatives of the Government Performance and... creation, expansion, or maintenance of foreign markets, FAS seeks to identify those projects that would...

Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis.

PubMed

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas-FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas-FasL in regulating Th17 and Treg cells' functions, in the context of MS.

Gemcitabine sensitizes lung cancer cells to Fas/FasL system-mediated killing

PubMed Central

Siena, Liboria; Pace, Elisabetta; Ferraro, Maria; Di Sano, Caterina; Melis, Mario; Profita, Mirella; Spatafora, Mario; Gjomarkaj, Mark

2014-01-01

Gemcitabine is a chemotherapy agent commonly used in the treatment of non-small cell lung cancer (NSCLC) that has been demonstrated to induce apoptosis in NSCLC cells by increasing functionally active Fas expression. The aim of this study was to evaluate the Fas/Fas ligand (FasL) system involvement in gemcitabine-induced lung cancer cell killing. NSCLC H292 cells were cultured in the presence or absence of gemcitabine. FasL mRNA and protein were evaluated by real-time PCR, and by Western blot and flow cytometry, respectively. Apoptosis of FasL-expressing cells was evaluated by flow cytometry, and caspase-8 and caspase-3 activation by Western blot and a colorimetric assay. Cytotoxicity of lymphokine-activated killer (LAK) cells and malignant pleural fluid lymphocytes against H292 cells was analysed in the presence or absence of the neutralizing anti-Fas ZB4 antibody, by flow cytometry. Gemcitabine increased FasL mRNA and total protein expression, the percentage of H292 cells bearing membrane-bound FasL (mFasL) and of mFasL-positive apoptotic H292 cells, as well as caspase-8 and caspase-3 cleavage. Moreover, gemcitabine increased CH11-induced caspase-8 and caspase-3 cleavage and proteolytic activity. Cytotoxicity of LAK cells and pleural fluid lymphocytes was increased against gemcitabine-treated H292 cells and was partially inhibited by ZB4 antibody. These results demonstrate that gemcitabine: (i) induces up-regulation of FasL in lung cancer cells triggering cell apoptosis via an autocrine/paracrine loop; (ii) induces a Fas-dependent apoptosis mediated by caspase-8 and caspase-3 activation; (iii) enhances the sensitivity of lung cancer cells to cytotoxic activity of LAK cells and malignant pleural fluid lymphocytes, partially via Fas/FasL pathway. Our data strongly suggest an active involvement of the Fas/FasL system in gemcitabine-induced lung cancer cell killing. PMID:24128051

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Salah, Ahmed; Nabhan, Marwa; Rasheed, Maha; Kamel, Solaf; Kandil, Dina; Thabet, Eman H

2016-07-01

An essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas -670A/G and Fas Ligand (FasL) -843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients. In 47 pediatric kidney transplant recipients and 20 healthy controls, Fas -670A/G and FasL -843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured. Serum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25±298.64pg/ml vs 143.17±44.55pg/ml, p=0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70±279.87pg/ml vs 507.85±342.80pg/ml, p=0.56). Fas -670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P>0.05 for all). FasL -843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P>0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P=0.03). FasL -843C/T alleles were significantly different between patients with and without AR (P=0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR. This study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-Fas Antibody Conjugated Nanoparticles Enhancing the Antitumor Effect of Camptothecin by Activating the Fas-FasL Apoptotic Pathway.

PubMed

Yu, Hongliang; He, Jian; Lu, Qian; Huo, Da; Yuan, Shanmei; Zhou, Zhengyang; Xu, Peipei; Hu, Yong

2016-11-09

Emerging evidence suggest that the introduction of Fas ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL-based therapeutic strategies. Herein, smart nanoparticles (NPs) with a sandwich structure were fabricated. These NPs consist of a matrix metalloproteinase (MMP) cleavable PEG outer layer, an anti-Fas antibody middle layer, and a camptothecin (CPT)-loaded inner core. They could accumulate at a tumor site by the enhanced permeability and retention (EPR) effect. The removable PEG layer protects the cytotoxic anti-Fas antibody from premature contact with normal tissues, thus avoiding the unexpected lethal side effect before they reach the tumor site. Due to the high level of MMP expressed by tumor cells inside the tumor tissue, these NPs would shed their PEG layers, resulting in the exposure of anti-Fas antibody to bind the Fas receptor and triggering the apoptosis of tumor cells. Results of Western blot confirmed that these NPs could mimic the function of activated cytotoxic lymphocyte (CTL) to activate the Fas-FasL apoptosis pathway of tumor cells. With the aid of CPT payload, these anti-Fas antibody conjugated NPs achieved a high tumor inhibition in the B16 allograft tumor animal model. The design of these NPs provides a method for delivering cytotoxic ligand to targeting tissue, which may be valuable in cancer therapy.

Comparison of Online Agricultural Information Services.

ERIC Educational Resources Information Center

Reneau, Fred; Patterson, Richard

1984-01-01

Outlines major online agricultural information services--agricultural databases, databases with agricultural services, educational databases in agriculture--noting services provided, access to the database, and costs. Benefits of online agricultural database sources (availability of agricultural marketing, weather, commodity prices, management…

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis.

PubMed

Bień, Karolina; Żmigrodzka, Magdalena; Orłowski, Piotr; Fruba, Aleksandra; Szymański, Łukasz; Stankiewicz, Wanda; Nowak, Zuzanna; Malewski, Tadeusz; Krzyżowska, Małgorzata

2017-08-01

The aim of this study was to elucidate the role of apoptosis mediated through Fas/FasL pathway using the mouse model of atopic dermatitis (AD). AD was induced by epicutaneous application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas-) and B6Smn.C3-Faslgld/J (FasL-) mouse strains. Skin samples were subjected to staining for Fas/FasL expression, M30 epitope and assessment of inflammatory response via immunohistochemical staining. Cytokine and chemokine production was assessed by real-time PCR. In comparison to wild-type mice, OVA sensitization of Fas- and FasL-deficient mice led to increased epidermal and dermal thickness, collagen deposition and local inflammation consisting of macrophages, neutrophils and CD4+ T cells. Fas- and FasL-deficient mice showed increased total counts of regulatory T cells (Tregs) and IgE levels in blood as well as increased expression of IL-1β, IL-4, IL-5, IL-13 and TGF-1β mRNA in comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10, IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased. Our results show that lack of the Fas-induced apoptosis leads to exacerbation of AD characteristics such as Th2 inflammation and dermal thickening. Therefore, Fas receptor can play an important role in AD pathogenesis by controlling development of the local inflammation.

78 FR 23885 - Agricultural Research Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... DEPARTMENT OF AGRICULTURE Agricultural Research Service Notice of Intent To Grant Exclusive License AGENCY: Agricultural Research Service, USDA. ACTION: Notice of intent. SUMMARY: Notice is hereby given that the U.S. Department of Agriculture, Agricultural Research Service, intends to grant to...

Relationship between Fas and Fas Ligand gene polymorphisms and pre-eclampsia.

PubMed

Masoumi, Elham; Tavakkol-Afshari, Jalil; Nikpoor, Amin Reza; Ghaffari-Nazari, Haniyeh; Tahaghoghi-Hajghorbani, Sahar; Jalali, Seyed Amir

2016-10-01

In normal pregnancy, the Th1 subtype, responsible for the production of inflammatory cytokines, is reduced, and the Th2 subtype is increased to prohibit inflammation. In pre-eclampsia, the Th1 cell population is increased; thus, subsequent inflammation and trophoblast destruction occur. Polymorphisms in the Fas and Fas Ligand (FasL) promoter regions can influence Fas and FasL expression and accused to increase of Th1 subtype. DNA samples from 153 pregnant women with pre-eclampsia and 140 controls were genotyped through polymerase chain reaction-restriction fragment length polymorphism. A Fisher's exact test was used to compare the distribution of individual polymorphisms. Fas-1377 AA, AG and GG genotypes were observed in 2.61%, 18.30% and 79.08% in the pre-eclampsia group opposed to 0%, 27.14% and 72.85% in the control group (P = 0.037), respectively. Fas-670 AA, AG and GG genotypes were observed in 37.9%, 41.8% and 20.3% of pre-eclampsia patients compared with 33.6%, 50.7% and 15.7% in healthy pregnant women (P = 0.291), respectively. No statically significant differences in the FasL-844 genotype were observed between the groups (P = 0.69). The Fas-1377G > A polymorphism is associated with a higher risk of pre-eclampsia. © 2016 Japan Society of Obstetrics and Gynecology.

Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer.

PubMed

Ohno, S; Tachibana, M; Shibakita, M; Dhar, D K; Yoshimura, H; Kinugasa, S; Kubota, H; Masunaga, R; Nagasue, N

2000-12-01

Previous studies indicate that gastric carcinomas express Fas ligand and down-regulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD8+ cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients' age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD8+ cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD8 + cells.

PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo

PubMed Central

Tao, Rong-Hua; Berkova, Zuzana; Wise, Jillian F.; Rezaeian, Abdol-Hossein; Daniluk, Urszula; Ao, Xue; Hawke, David H.; Karp, Judith E.; Lin, Hui-Kuan; Molldrem, Jeffrey J.

2011-01-01

Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML–retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)–derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIPL/S and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas. PMID:21803845

FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma

PubMed Central

Sehgal, Lalit; Mathur, Rohit; Braun, Frank K.; Wise, Jillian F.; Berkova, Zuzana; Neelapu, Sattva; Kwak, Larry W.; Samaniego, Felipe

2018-01-01

Impaired Fas-mediated apoptosis is associated with poor clinical outcomes and cancer chemoresistance. Soluble Fas receptor (sFas), produced by skipping of exon 6, inhibits apoptosis by sequestering Fas ligand. Serum sFas is associated with poor prognosis of non-Hodgkin's lymphomas. We found that the alternative splicing of Fas in lymphomas is tightly regulated by a lncRNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton’s tyrosine kinase (BTK) inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas thereby enhances Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing. PMID:24811343

Inhibition of Fas (CD95) expression and Fas-mediated apoptosis by oncogenic Ras.

PubMed

Fenton, R G; Hixon, J A; Wright, P W; Brooks, A D; Sayers, T J

1998-08-01

The ras oncogene plays an important role in the multistep progression to cancer by activation of signal transduction pathways that contribute to aberrant growth regulation. Although many of these effects are cell autonomous, the ras oncogene also regulates the expression of genes that alter host/tumor interactions. We now extend the mechanisms through which ras promotes tumor survival by demonstrating that oncogenic Ras inhibits expression of the fas gene and renders Ras-transformed cells resistant to Fas-induced apoptosis. A panel of Ras-transformed clones exhibited a marked inhibition in fas mRNA and Fas cell surface expression as compared with untransformed parental cell lines. Fas expression was induced by culture in the presence of IFN-gamma + tumor necrosis factor alpha; however, the maximal level attained in Ras transformants was approximately 10-fold below the level of untransformed cells. Whereas untransformed cells were sensitive to apoptotic death induced by cross-linking surface Fas (especially after cytokine treatment), Ras-transformed cells were very resistant to Fas-induced death even under the most stringent assay conditions. To demonstrate that this resistance was mediated by oncogenic Ras and not secondary genetic events, pools of Ras-transformed cells were generated using a highly efficient retroviral transduction technique. Transformed pools were assayed 6 days after infection and demonstrated a marked decrease in fas gene expression and Fas-mediated apoptosis. Oncogenic Ras did not promote general resistance to apoptosis, because ectopic expression of a fas cDNA in Ras-transformed cells restored sensitivity to Fas-induced apoptosis. These data indicate that oncogenic Ras inhibits basal levels of expression of the fas gene, and although cytokine signal transduction pathways are functional in these cells, the level of surface Fas expression remains below the threshold required for induction of apoptosis. These data identify a mechanism by which

Radiation and stress-induced apoptosis: A role for Fas/Fas ligand interactions

PubMed Central

Reap, Elizabeth A.; Roof, Kevin; Maynor, Kenrick; Borrero, Michelle; Booker, Jessica; Cohen, Philip L.

1997-01-01

The lpr gene encodes a defective form of Fas, a cell surface protein that mediates apoptosis. This defect blocks apoptotic deletion of autoreactive T and B cells, leading to lymphoproliferation and lupus-like autoantibody production. The effects of the lpr Fas mutation on other kinds of physiologically relevant apoptosis are largely undocumented. To assess whether some of the apoptosis known to occur after ionizing radiation might be mediated by Fas/Fas ligand (FasL) interactions, we quantitated in vitro apoptosis by flow cytometry measurement of DNA content in splenic T and B cells from irradiated 5- to 8-month-old B6/lpr mice. Total apoptosis of both lpr and control cells was substantial after treatment; however there was a significant difference between B6 (73%) and lpr (25%) lymphocyte apoptosis. Thy1, CD4, CD8, and IgM cells from lpr showed much lower levels of apoptosis than control cells after irradiation. Apoptosis induced by heat shock was also impaired in lpr. The finding that γ-irradiation increased Fas expression on B6 cells and that irradiation-induced apoptosis could be blocked with a Fas–Fc fusion protein further supported the possible involvement of Fas in this form of apoptosis. Fas/FasL interactions may thus play an important role in identifying and eliminating damaged cells after γ-irradiation and other forms of injury. PMID:9159145

FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

PubMed Central

Banzato, Priscilla Chamelete Andrade; Daher, Silvia; Traina, Évelyn; Torloni, Maria Regina; Gueuvoghlanian-Silva, Bárbara Yasmin; Puccini, Renata Fiorini; Pendeloski, Karen Priscilla Tezotto

2013-01-01

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case–control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules. PMID:23420824

NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression*

PubMed Central

Liu, Feiyan; Bardhan, Kankana; Yang, Dafeng; Thangaraju, Muthusamy; Ganapathy, Vadivel; Waller, Jennifer L.; Liles, Georgia B.; Lee, Jeffrey R.; Liu, Kebin

2012-01-01

Fas is a member of the death receptor family. Stimulation of Fas leads to induction of apoptotic signals, such as caspase 8 activation, as well as “non-apoptotic” cellular responses, notably NF-κB activation. Convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-κB activity. On the other hand, compelling data have also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. Furthermore, although stimulation of Fas activates NF-κB, the function of NF-κB in the Fas-mediated apoptosis pathway remains largely undefined. In this study, we observed that deficiency of either Fas or FasL resulted in significantly increased incidence of 3-methylcholanthrene-induced spontaneous sarcoma development in mice. Furthermore, Fas-deficient mice also exhibited significantly greater incidence of azoxymethane and dextran sodium sulfate-induced colon carcinoma. In addition, human colorectal cancer patients with high Fas protein in their tumor cells had a longer time before recurrence occurred. Engagement of Fas with FasL triggered NF-κB activation. Interestingly, canonical NF-κB was found to directly bind to the FAS promoter. Blocking canonical NF-κB activation diminished Fas expression, whereas blocking alternate NF-κB increased Fas expression in human carcinoma cells. Moreover, although canonical NF-κB protected mouse embryo fibroblast (MEF) cells from TNFα-induced apoptosis, knocking out p65 diminished Fas expression in MEF cells, resulting in inhibition of FasL-induced caspase 8 activation and apoptosis. In contrast, knocking out p52 increased Fas expression in MEF cells. Our observations suggest that canonical NF-κB is a Fas transcription activator and alternate NF-κB is a Fas transcription repressor, and Fas functions as a suppressor of spontaneous sarcoma and colon carcinoma. PMID:22669972

Decision Support Tools Evaluation Report for FAS/PECAD, Version 2.0

NASA Technical Reports Server (NTRS)

Ross, Kenton; McKellip, Rodney; Mason, Ted; Zanoni, Vicki; Morris, Keith

2004-01-01

Global agricultral intelligence is a key element of decision support eithin the U.S. Department of Agriculture (USDA). Estimeates of production and yield issued by the USDA for both foreign and domestic agriculture are primary sources of information for policy and management decision making. The USDA monitors the major global agricultural commodities through the Production Estimates and Crop Assessment Division (PECAD) of its Foreign Agricultural Service (FAS). Specifically, PECAD iintelligence focuses on global agricultural production and on conditions that affect food security. In conjunction with the USDA, NASA is evaluating the potential for products from NASA's Earth Science Enterprise (ESE) missions to add value to PECAD's decision support tools. NASA is usig a systems engineering approach to evaluate the potential enhancement of PECAD's decision support system (DSS)-first by understanding the components of the system and its input requirements, then by recommending NASA products that may be integrated as system inputs to improve the accuracy, quality, or efficiency of the DSS output. This report documents the evaluation phase of the systems engineering process and includes an examination of the system architecture, operations, and input requirements, as well as an initial assessment of specific ESE measurement systems and products that should be considered for their potential to enhance the PECAD DSS.

Dysregulation of the Fas/FasL system in an experimental animal model of HELLP syndrome.

PubMed

Gibbens, Jacob; Morris, Rachael; Bowles, Teylor; Spencer, Shauna-Kay; Wallace, Kedra

2017-04-01

Placental FasL is up-regulated in women with HELLP (hemolysis elevated liver enzyme and low platelet) syndrome and has been proposed to contribute to the liver damage seen in these patients. This study aimed to determine if an experimental rodent model of HELLP also had dysregulation of Fas/FasL compared to normal pregnant (NP) rats. We also set out to determine if blockade of the endothelin system regulated Fas/FasL expression in HELLP rats. On gestational day (GD) 12, sEng (7ug/kg) and sFlt-1 (4.7ug/kg) infusion began via mini-osmotic pump into NP rats. On GD19 plasma and tissue were collected and FasL and Fas were measured via enzyme linked immunosorbent assay and gene expression via real-time PCR. HELLP rats had significantly more circulating and placental FasL compared to NP rats, whereas hepatic FasL was decreased and placental Fas was increased compared to NP rats. Administration of an endothelin A receptor antagonist (ET A ) beginning on GD12 significantly decreased placental expression of Fas in HELLP rats. Liver mRNA transcript of Fas was significantly increased in HELLP rats compared to NP rats. These data suggest that rats in this experimental model of HELLP syndrome have abnormal expression of the Fas/FasL system. Future studies will examine the sources of Fas/FasL dysregulation in this model and if blockade could reduce some of the inflammation and hypertension associated with HELLP syndrome. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters.

PubMed

Zepeda-Nuño, José Sergio; Guerrero-Velázquez, Celia; Del Toro-Arreola, Susana; Vega-Magaña, Natali; Ángeles-Sánchez, Julián; Haramati, Jesse; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R

2017-04-01

ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2), ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (III-IV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.

Association between Fas/FasL gene polymorphism and musculoskeletal degenerative diseases: a meta-analysis.

PubMed

Huang, Donghua; Xiao, Jinrong; Deng, Xiangyu; Ma, Kaige; Liang, Hang; Shi, Deyao; Wu, Fashuai; Shao, Zengwu

2018-05-07

It was reported that Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) gene polymorphism might be related to the risk of musculoskeletal degenerative diseases (MSDD), such as osteoarthritis (OA), intervertebral disc degeneration (IVDD) and rheumatoid arthritis (RA). However, data from different studies was inconsistent. Here we aim to elaborately summarize and explore the association between the Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) and MSDD. Literatures were selected from PubMed, Web of Science, Embase, Scopus and Medline in English and VIP, SinoMed, Wanfang and the China National Knowledge Infrastructure (CNKI) in Chinese up to August 21, 2017. All the researches included are case-control studies about human. We calculated the pooled odds ratios (ORs) with 95% confidence intervals (95% CI) to evaluate the strengths of the associations of Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) polymorphisms with MSDD risk. Eleven eligible studies for rs1800682 with 1930 cases and 1720 controls, 6 eligible studies for rs2234767 with 1794 cases and 1909 controls, 3 eligible studies for rs5030772 with 367 cases and 313 controls and 8 eligible studies for rs763110 with 2010 cases and 2105 controls were included in this analysis. The results showed that the G allele of Fas (rs1800682) is associated with an increased risk of IVDD in homozygote and recessive models. The G allele of Fas (rs2234767) is linked to a decreased risk of RA but an enhanced risk of OA in allele and recessive models. In addition, the T allele of FasL (rs763110) is correlated with a reduced risk of IVDD in all of models. However, no relationship was found between FasL (rs5030772) and these three types of MSDD in any models. Fas (rs1800682) and FasL (rs763110) polymorphism were associated with the risk of IVDD and Fas (rs2234767) was correlated to the susceptibility of OA and RA. Fas (rs1800682) and Fas (rs2234767) are more likely to be associated with MSDD for Chinese

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study.

PubMed

Han, Ae Ra; Choi, Young Min; Hong, Min A; Kim, Jin Ju; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan

2018-05-20

Aberrant apoptosis at the trophoblast-maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy-Weinberg equilibrium. Fas -670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas -1377 G/A and FasL -844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.

Fas/FasL gene polymorphism in patients with Hashimoto's thyroiditis in Turkish population.

PubMed

Erdogan, M; Kulaksizoglu, M; Ganidagli, S; Berdeli, A

2017-01-01

Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. This study aims to evaluate the influence of Fas and FasL gene polymorphism in Hashimoto's thyroiditis in Turkish population. A total of 112 patients with Hashimoto's thyroiditis and 112 cases of healthy control people were included in this study. The evaluation of genotype for Fas -670 A/G and FasL 843 C/T gene polymorphism was performed by using PCR-RFLP method. The FAS genotype and gene allele frequency distribution did differ between the control group (AA 36.6 %, AG 50.0 %, GG 13.4 %, A 61.6 %, G 38.4 %) and the Hashimoto's thyroiditis patients (AA 21.4 %, AG 50.9 %, GG 27.7 %, A 46.9 %, G 53.1 %) (p < 0.01). The evaluation of FasL genotype and gene allele frequency did not show statistically significant difference between the patient group (CC 27.7 %, CT 45.5 %, TT 26.8 %, C 50.4 %, T 49.6 %) and control group (CC 33.9 %, CT 44.6 %, TT 21,4 %, C 56.3 %, T 43.8 %) (p > 0.05). Gene polymorphism of Fas and G allele frequency may play a role in the regulation of apoptosis in thyroid autoimmune disorders. There is a need for further studies to clarify the genetic role of apoptosis in HT.

Impaired Fas-Fas Ligand Interactions Result in Greater Recurrent Herpetic Stromal Keratitis in Mice

PubMed Central

Yin, Xiao-Tang; Keadle, Tammie L.; Hard, Jessicah; Herndon, John; Potter, Chloe A.; Del Rosso, Chelsea R.; Ferguson, Thomas A.; Stuart, Patrick M.

2015-01-01

Herpes simplex virus-1 (HSV-1) infection of the cornea leads to a potentially blinding condition termed herpetic stromal keratitis (HSK). Clinical studies have indicated that disease is primarily associated with recurrent HSK following reactivation of a latent viral infection of the trigeminal ganglia. One of the key factors that limit inflammation of the cornea is the expression of Fas ligand (FasL). We demonstrate that infection of the cornea with HSV-1 results in increased functional expression of FasL and that mice expressing mutations in Fas (lpr) and FasL (gld) display increased recurrent HSK following reactivation compared to wild-type mice. Furthermore, both gld and lpr mice took longer to clear their corneas of infectious virus and the reactivation rate for these strains was significantly greater than that seen with wild-type mice. Collectively, these findings indicate that the interaction of Fas with FasL in the cornea restricts the development of recurrent HSK. PMID:26504854

Impaired Fas-Fas Ligand Interactions Result in Greater Recurrent Herpetic Stromal Keratitis in Mice.

PubMed

Yin, Xiao-Tang; Keadle, Tammie L; Hard, Jessicah; Herndon, John; Potter, Chloe A; Del Rosso, Chelsea R; Ferguson, Thomas A; Stuart, Patrick M

2015-01-01

Herpes simplex virus-1 (HSV-1) infection of the cornea leads to a potentially blinding condition termed herpetic stromal keratitis (HSK). Clinical studies have indicated that disease is primarily associated with recurrent HSK following reactivation of a latent viral infection of the trigeminal ganglia. One of the key factors that limit inflammation of the cornea is the expression of Fas ligand (FasL). We demonstrate that infection of the cornea with HSV-1 results in increased functional expression of FasL and that mice expressing mutations in Fas (lpr) and FasL (gld) display increased recurrent HSK following reactivation compared to wild-type mice. Furthermore, both gld and lpr mice took longer to clear their corneas of infectious virus and the reactivation rate for these strains was significantly greater than that seen with wild-type mice. Collectively, these findings indicate that the interaction of Fas with FasL in the cornea restricts the development of recurrent HSK.

Global Agricultural Monitoring (GLAM) using MODAPS and LANCE Data Products

NASA Astrophysics Data System (ADS)

Anyamba, A.; Pak, E. E.; Majedi, A. H.; Small, J. L.; Tucker, C. J.; Reynolds, C. A.; Pinzon, J. E.; Smith, M. M.

2012-12-01

The Global Inventory Modeling and Mapping Studies / Global Agricultural Monitoring (GIMMS GLAM) system is a web-based geographic application that offers Moderate Resolution Imaging Spectroradiometer (MODIS) imagery and user interface tools to data query and plot MODIS NDVI time series. The system processes near real-time and science quality Terra and Aqua MODIS 8-day composited datasets. These datasets are derived from the MOD09 and MYD09 surface reflectance products which are generated and provided by NASA/GSFC Land and Atmosphere Near Real-time Capability for EOS (LANCE) and NASA/GSFC MODIS Adaptive Processing System (MODAPS). The GIMMS GLAM system is developed and provided by the NASA/GSFC GIMMS group for the U.S. Department of Agriculture / Foreign Agricultural Service / International Production Assessment Division (USDA/FAS/IPAD) Global Agricultural Monitoring project (GLAM). The USDA/FAS/IPAD mission is to provide objective, timely, and regular assessment of the global agricultural production outlook and conditions affecting global food security. This system was developed to improve USDA/FAS/IPAD capabilities for making operational quantitative estimates for crop production and yield estimates based on satellite-derived data. The GIMMS GLAM system offers 1) web map imagery including Terra & Aqua MODIS 8-day composited NDVI, NDVI percent anomaly, and SWIR-NIR-Red band combinations, 2) web map overlays including administrative and 0.25 degree Land Information System (LIS) shape boundaries, and crop land cover masks, and 3) user interface tools to select features, data query, plot, and download MODIS NDVI time series.

A lack of Fas/FasL signalling leads to disturbances in the antiviral response during ectromelia virus infection.

PubMed

Bień, K; Sobańska, Z; Sokołowska, J; Bąska, P; Nowak, Z; Winnicka, A; Krzyzowska, M

2016-04-01

Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. Fas receptor-Fas ligand (FasL) signaling is involved in apoptosis of immune cells and virus-specific cytotoxicity. The Fas/FasL pathway also plays an important role in controlling the local inflammatory response during ECTV infection. Here, the immune response to the ECTV Moscow strain was examined in Fas (-) (lpr), FasL (-) (gld) and C57BL6 wild-type mice. During ECTV-MOS infection, Fas- and FasL mice showed increased viral titers, decreased total numbers of NK cells, CD4(+) and CD8(+) T cells followed by decreased percentages of IFN-γ expressing NK cells, CD4(+) and CD8(+) T cells in spleens and lymph nodes. At day 7 of ECTV-MOS infection, Fas- and FasL-deficient mice had the highest regulatory T cell (Treg) counts in spleen and lymph nodes in contrast to wild-type mice. Furthermore, at days 7 and 10 of the infection, we observed significantly higher numbers of PD-L1-expressing dendritic cells in Fas (-) and FasL (-) mice in comparison to wild-type mice. Experiments in co-cultures of CD4(+) T cells and bone-marrow-derived dendritic cells showed that the lack of bilateral Fas-FasL signalling led to expansion of Tregs. In conclusion, our results demonstrate that during ECTV infection, Fas/FasL can regulate development of tolerogenic DCs and Tregs, leading to an ineffective immune response.

Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever.

PubMed

Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, Ramazan

2017-08-05

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant

Research on the development and preliminary application of Beijing agricultural sci-tech service hotline WebApp in agricultural consulting services

NASA Astrophysics Data System (ADS)

Yu, Weishui; Luo, Changshou; Zheng, Yaming; Wei, Qingfeng; Cao, Chengzhong

2017-09-01

To deal with the “last kilometer” problem during the agricultural science and technology information service, we analyzed the feasibility, necessity and advantages of WebApp applied to agricultural information service and discussed the modes of WebApp used in agricultural information service based on the requirements analysis and the function of WebApp. To overcome the existing App’s defects of difficult installation and weak compatibility between the mobile operating systems, the Beijing Agricultural Sci-tech Service Hotline WebApp was developed based on the HTML and JAVA technology. The WebApp has greater compatibility and simpler operation than the Native App, what’s more, it can be linked to the WeChat public platform making it spread easily and run directly without setup process. The WebApp was used to provide agricultural expert consulting services and agriculture information push, obtained a good preliminary application achievement. Finally, we concluded the creative application of WebApp in agricultural consulting services and prospected the development of WebApp in agricultural information service.

The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

PubMed

Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

2016-02-01

In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

Pigment Epithelial-derived Factor (PEDF)-triggered Lung Cancer Cell Apoptosis Relies on p53 Protein-driven Fas Ligand (Fas-L) Up-regulation and Fas Protein Cell Surface Translocation*

PubMed Central

Li, Lei; Yao, Ya-Chao; Fang, Shu-Huan; Ma, Cai-Qi; Cen, Yi; Xu, Zu-Min; Dai, Zhi-Yu; Li, Cen; Li, Shuai; Zhang, Ting; Hong, Hong-Hai; Qi, Wei-Wei; Zhou, Ti; Li, Chao-Yang; Yang, Xia; Gao, Guo-Quan

2014-01-01

Pigment epithelium-derived factor (PEDF), a potent antiangiogenesis agent, has recently attracted attention for targeting tumor cells in several types of tumors. However, less is known about the apoptosis-inducing effect of PEDF on human lung cancer cells and the underlying molecular events. Here we report that PEDF has a growth-suppressive and proapoptotic effect on lung cancer xenografts. Accordingly, in vitro, PEDF apparently induced apoptosis in A549 and Calu-3 cells, predominantly via the Fas-L/Fas death signaling pathway. Interestingly, A549 and Calu-3 cells are insensitive to the Fas-L/Fas apoptosis pathway because of the low level of cell surface Fas. Our results revealed that, in addition to the enhancement of Fas-L expression, PEDF increased the sensitivity of A549 and Calu-3 cells to Fas-L-mediated apoptosis by triggering the translocation of Fas protein to the plasma membrane in a p53- and FAP-1-dependent manner. Similarly, the up-regulation of Fas-L by PEDF was also mediated by p53. Furthermore, peroxisome proliferator-activated receptor γ was determined to be the upstream regulator of p53. Together, these findings uncover a novel mechanism of tumor cell apoptosis induced by PEDF and provide a potential therapeutic strategy for tumors that are insensitive to Fas-L/Fas-dependent apoptosis because of a low level of cell surface Fas. PMID:25225287

D4F alleviates macrophage-derived foam cell apoptosis by inhibiting the NF-κB-dependent Fas/FasL pathway.

PubMed

Tian, Hua; Yao, Shu-Tong; Yang, Na-Na; Ren, Jie; Jiao, Peng; Zhang, Xiangjian; Li, Dong-Xuan; Zhang, Gong-An; Xia, Zhen-Fang; Qin, Shu-Cun

2017-08-04

This study was designed to explore the protective effect of D4F, an apolipoprotein A-I mimetic peptide, on nuclear factor-κB (NF-κB)-dependent Fas/Fas ligand (FasL) pathway-mediated apoptosis in macrophages induced by oxidized low-density lipoprotein (ox-LDL). Our results showed that ox-LDL induced apoptosis, NF-κB P65 nuclear translocation and the upregulation of Fas/FasL pathway-related proteins, including Fas, FasL, Fas-associated death domain proteins (FADD), caspase-8 and caspase-3 in RAW264.7 macrophages, whereas silencing of Fas blocked ox-LDL-induced macrophage apoptosis. Furthermore, silencing of P65 attenuated macrophage apoptosis and the upregulation of Fas caused by ox-LDL, whereas P65 expression was not significantly affected by treatment with Fas siRNA. D4F attenuated the reduction of cell viability and the increase in lactate dehydrogenase leakage and apoptosis. Additionally, D4F inhibited ox-LDL-induced P65 nuclear translocation and upregulation of Fas/FasL pathway-related proteins in RAW264.7 cells and in atherosclerotic lesions of apoE -/- mice. However, Jo2, a Fas-activating monoclonal antibody, reversed the inhibitory effect of D4F on ox-LDL-induced cell apoptosis and upregulation of Fas, FasL and FADD. These data indicate that NF-κB mediates Fas/FasL pathway activation and apoptosis in macrophages induced by ox-LDL and that D4F protects macrophages from ox-LDL-induced apoptosis by suppressing the activation of NF-κB and the Fas/FasL pathway.

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

Code of Federal Regulations, 2011 CFR

2011-01-01

... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and Property... must an executive agency do to implement the eFAS program? (a) An executive agency must review the... value added services) of the eFAS SCs. Agencies should give full consideration to sales solutions...

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and Property... must an executive agency do to implement the eFAS program? (a) An executive agency must review the... value added services) of the eFAS SCs. Agencies should give full consideration to sales solutions...

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

Code of Federal Regulations, 2014 CFR

2014-01-01

... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and Property... must an executive agency do to implement the eFAS program? (a) An executive agency must review the... value added services) of the eFAS SCs. Agencies should give full consideration to sales solutions...

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and Property... must an executive agency do to implement the eFAS program? (a) An executive agency must review the... value added services) of the eFAS SCs. Agencies should give full consideration to sales solutions...

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

Code of Federal Regulations, 2012 CFR

2012-01-01

... agency do to implement the eFAS program? 102-38.360 Section 102-38.360 Public Contracts and Property... must an executive agency do to implement the eFAS program? (a) An executive agency must review the... value added services) of the eFAS SCs. Agencies should give full consideration to sales solutions...

Fas/FasL interaction mediates imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells.

PubMed

Dou, Rui; Hong, Zhenya; Tan, Xiaosheng; Hu, Fenfen; Ding, Yajie; Wang, Wei; Liang, Zhihui; Zhong, Rongrong; Wu, Xiongwen; Weng, Xiufang

2018-07-01

The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4). Human iNKT cells exhibited more intensive cytotoxicity and less efficient cytokine production in response to Fas-bearing Jurkat cells than those to the Fas-negative tumor cells (Molt-4 and myeloid-derived K562). The imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells were CD1d-dependent and relied mostly on Fas/FasL interaction. The impairment in cytokine production could be overcome by Fas/FasL blocking antibodies and exogenous IL-2. Elevated CD1d levels as well as CD1d and Fas co-localization were found in T-cell lymphomas. However, defects in frequency and function of circulating iNKT cells were observed in the patients, which could be partly rescued by exogenous IL-2. Collectively, the Fas/FasL-dependent aberrant iNKT cell responses and the reversibility of the defects suggest the distinct iNKT cell manipulation in CD1d- and Fas-bearing T cell malignancies. Copyright © 2018. Published by Elsevier Ltd.

Ecosystem services and agriculture: tradeoffs and synergies

PubMed Central

Power, Alison G.

2010-01-01

Agricultural ecosystems provide humans with food, forage, bioenergy and pharmaceuticals and are essential to human wellbeing. These systems rely on ecosystem services provided by natural ecosystems, including pollination, biological pest control, maintenance of soil structure and fertility, nutrient cycling and hydrological services. Preliminary assessments indicate that the value of these ecosystem services to agriculture is enormous and often underappreciated. Agroecosystems also produce a variety of ecosystem services, such as regulation of soil and water quality, carbon sequestration, support for biodiversity and cultural services. Depending on management practices, agriculture can also be the source of numerous disservices, including loss of wildlife habitat, nutrient runoff, sedimentation of waterways, greenhouse gas emissions, and pesticide poisoning of humans and non-target species. The tradeoffs that may occur between provisioning services and other ecosystem services and disservices should be evaluated in terms of spatial scale, temporal scale and reversibility. As more effective methods for valuing ecosystem services become available, the potential for ‘win–win’ scenarios increases. Under all scenarios, appropriate agricultural management practices are critical to realizing the benefits of ecosystem services and reducing disservices from agricultural activities. PMID:20713396

Quantitative assessment of the relationship between Fas/FasL genes polymorphisms and head and neck cancer risk.

PubMed

Zhang, Dan-Feng; Jiang, Guang-Bin; Qin, Chuan-Qi; Liu, De-Xi; Hu, Ya-Jun; Zhou, Juan; Niu, Yu-Ming

2018-02-01

Molecular epidemiological studies have demonstrated a closer association between Fas/FasL polymorphisms and head and neck cancer (HNC) risk, and the results of these published studies were inconsistent. We therefore performed this meta-analysis to explore the associations between Fas/FasL polymorphisms and HNC risk. Four online databases (PubMed, Embase, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (95% CIs) were calculated to assess the association between Fas -670A>G, Fas -1377G>A, and FasL -844C>T polymorphisms and HNC risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 9 related publications (20 independent case-control studies) involving 3179 patients and 4217 controls were identified. Significant association of protective effects was observed between FasL -844C>T polymorphism and HNC risk in codominant and dominant model models (CT vs CC: OR = 0.89, 95% CI = 0.79-1.00, P = .05, I = 38.3%, CT+TT vs CC: OR = 0.88, 95% CI = 0.79-0.98, P = .02, I = 35.8%). Furthermore, the similar protective effects were observed the subgroup analysis of in Asian population and population-based controls group. Our meta-analysis indicated that FasL -844C>T polymorphism plays a protective role against HNC development, but the Fas -670A>G and Fas -1377G>A polymorphisms maybe not associated with HNC risk.

Quantitative assessment of the relationship between Fas/FasL genes polymorphisms and head and neck cancer risk

PubMed Central

Zhang, Dan-Feng; Jiang, Guang-Bin; Qin, Chuan-Qi; Liu, De-Xi; Hu, Ya-Jun; Zhou, Juan; Niu, Yu-Ming

2018-01-01

Abstract Background: Molecular epidemiological studies have demonstrated a closer association between Fas/FasL polymorphisms and head and neck cancer (HNC) risk, and the results of these published studies were inconsistent. We therefore performed this meta-analysis to explore the associations between Fas/FasL polymorphisms and HNC risk. Methods: Four online databases (PubMed, Embase, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (95% CIs) were calculated to assess the association between Fas -670A>G, Fas -1377G>A, and FasL -844C>T polymorphisms and HNC risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Results: Overall, 9 related publications (20 independent case–control studies) involving 3179 patients and 4217 controls were identified. Significant association of protective effects was observed between FasL -844C>T polymorphism and HNC risk in codominant and dominant model models (CT vs CC: OR = 0.89, 95% CI = 0.79–1.00, P = .05, I2 = 38.3%, CT+TT vs CC: OR = 0.88, 95% CI = 0.79–0.98, P = .02, I2 = 35.8%). Furthermore, the similar protective effects were observed the subgroup analysis of in Asian population and population-based controls group. Conclusion: Our meta-analysis indicated that FasL -844C>T polymorphism plays a protective role against HNC development, but the Fas -670A>G and Fas -1377G>A polymorphisms maybe not associated with HNC risk. PMID:29419701

Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis.

PubMed

Musiał, Kinga; Zwolińska, Danuta

2011-07-01

The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis--neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA. Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations. Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms.

Interferon-gamma induces apoptosis and augments the expression of Fas and Fas ligand by microglia in vitro.

PubMed

Badie, B; Schartner, J; Vorpahl, J; Preston, K

2000-04-01

Activation of microglia by interferon-gamma (IFN-gamma) has been implicated in a number of central nervous system (CNS) inflammatory disease processes. Because IFN-gamma has also been shown to play a role in programmed cell death, we investigated its cytotoxicity and its effect on the Fas apoptotic pathway in microglia. Flow cytometry was used to quantify the IFN-gamma-mediated apoptotic response and Fas and Fas ligand (FasL) expression in two well-characterized murine microglia cell lines (BV-2 and N9). Nuclear fragmentation, suggestive of apoptosis, was noted within 24 h of incubation of microglia with IFN-gamma (10 U/ml). After a 72-h incubation, almost every BV-2 and N9 microglia, but not GL261 glioma cells, underwent cell death and detached from the culture plates. This cytotoxicity occurred even at low IFN-gamma concentrations (1 U/ml) and was inhibited by BAF, a pan-caspase inhibitor. Incubation of BV-2 and N9 microglia, but not GL261 glioma cells, with IFN-gamma also potentiated the expression of Fas and FasL in a similar dose-response and time-course manner, as seen for the apoptotic response. Whereas Fas expression increased by 100% in both microglia cells, FasL upregulation was more pronounced and increased by as much as 200% in the N9 cells. These findings suggest that in addition to its role as a microglia activator, IFN-gamma may also induce apoptosis of microglia, possibly through simultaneous upregulation of Fas and FasL. Interferon-gamma modulation of the Fas pathway and apoptosis in microglia may be important in the pathogenesis of inflammatory CNS disease processes. Copyright 2000 Academic Press.

Expression of Fas and Fas-ligand in donor hematopoietic stem and progenitor cells is dissociated from the sensitivity to apoptosis.

PubMed

Pearl-Yafe, Michal; Yolcu, Esma S; Stein, Jerry; Kaplan, Ofer; Shirwan, Haval; Yaniv, Isaac; Askenasy, Nadir

2007-10-01

The interaction between the Fas receptor and its cognate ligand (FasL) has been implicated in the mutual suppression of donor and host hematopoietic cells after transplantation. Following the observation of deficient early engraftment of Fas and FasL-defective donor cells and recipients, we determined the role of the Fas-FasL interaction. Donor cells were recovered after syngeneic (CD45.1-->CD45.2) transplants from various organs and assessed for expression of Fas/FasL in reference to lineage markers, carboxyfluorescein succinimidyl ester dilution, Sca-1 and c-kit expression. Naïve and bone marrow-homed cells were challenged for apoptosis ex vivo. The Fas receptor and ligand were markedly upregulated to 40% to 60% (p < 0.001 vs 5-10% in naïve cells) within 2 days after syngeneic transplantation, while residual host cells displayed modest and delayed upregulation of these molecules ( approximately 10%). All lin(-)Sca(+)c-kit(+) cells were Fas(+)FasL(+), including 95% of Sca-1(+) and 30% of c-kit(+) cells. Fas and FasL expression varied in donor cells that homed to bone marrow, spleen, liver and lung, and was induced by interaction with the stroma, irradiation, cell cycling, and differentiation. Bone marrow-homed donor cells challenged with supralethal doses of FasL were insensitive to apoptosis (3.2% +/- 1% vs 38% +/- 5% in naïve bone marrow cells), and engraftment was not affected by pretransplantation exposure of donor cells to an apoptotic challenge with FasL. There was no evidence of Fas-mediated suppression of donor and host cell activity after transplantation. Resistance to Fas-mediated apoptosis evolves as a functional characteristic of hematopoietic reconstituting stem and progenitor cells, providing them competitive engraftment advantage over committed progenitors.

Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-{kappa}B in HepG2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng Gong, E-mail: gong-feng@northwestern.edu; Anong Biotech Institute, Tianjin; Li Ying

Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apoptosis. Fas receptor (Fas) and Fas ligand (FasL) system is a critical signaling network triggering apoptosis. In current study, we investigated whether nodularin can induce Fas and FasL expression in HepG2 cell, a well used in vitro model for the study of human hepatocytes. Our data showed nodularinmore » induced Fas and FasL expression, at both mRNA and protein level, in a time- and dose-dependent manner. We also found nodularin induced apoptosis at the concentration and incubation time that Fas and FasL were significantly induced. Neutralizing antibody to FasL reduced nodularin-induced apoptosis. Further studies demonstrated that nodularin promoted nuclear translocation and activation of p65 subunit of NF-{kappa}B. By applying siRNA targeting p65, which knocked down p65 in HepG2 cells, we successfully impaired the activation of NF-{kappa}B by nodularin. In these p65 knockdown cells, we observed that Fas and FasL expression and apoptosis induced by nodularin were significantly reduced. These findings suggest the induction of Fas and FasL expression and thus cell apoptosis in HepG2 cells by nodularin is mediated through NF-{kappa}B pathway.« less

The Btk-dependent PIP5K1γ lipid kinase activation by Fas counteracts FasL-induced cell death.

PubMed

Rossin, Aurélie; Lounnas, Nadia; Durivault, Jérôme; Miloro, Giorgia; Gagnoux-Palacios, Laurent; Hueber, Anne-Odile

2017-11-01

The Fas/FasL system plays a critical role in death by apoptosis and immune escape of cancer cells. The Fas receptor being ubiquitously expressed in tissues, its apoptotic-inducing function, initiated upon FasL binding, is tightly regulated by several negative regulatory mechanisms to prevent inappropriate cell death. One of them, involving the non-receptor tyrosine kinase Btk, was reported mainly in B cells and only poorly described. We report here that Btk negatively regulates, through its tyrosine kinase activity, the FasL-mediated cell death in epithelial cell lines from colon cancer origin. More importantly, we show that Btk interacts not only with Fas but also with the phosphatidylinositol-4-phosphate 5-kinase, PIP5K1γ, which, upon stimulation by Fas ligand, is responsible of a rapid and transient synthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ). This production requires both the presence and the tyrosine kinase activity of Btk, and participates in the negative regulation of FasL-mediated cell death since knocking down PIP5K1γ expression significantly strengthens the apoptotic signal upon FasL engagement. Altogether, our data demonstrate the cooperative role of Btk and PIP5K1γ in a FasL-induced PI(4,5)P 2 production, both proteins participating to the threshold setting of FasL-induced apoptotic commitment in colorectal cell lines.

The role of the Fas/FasL signaling pathway in environmental toxicant-induced testicular cell apoptosis: An update.

PubMed

Wang, Mei; Su, Ping

2018-04-01

The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis. Consequently, degeneration of testicular somatic (Sertoli and Leydig) and spermatogenic cells, leads to decreased numbers of mature sperm and subsequently translates into infertility issues. Collectively, these findings illustrate that it is beneficial to develop potential targets for a new generation of new pharmaceutical therapies that would alleviate testicular dysfunctions. BTB: blood-testis barrier; DD: death domains; DR3: death receptor 3; DR4: death receptor 4; DR5: death receptor 5; DED: death effector domain; DISC: death-inducing signaling complex; ERα: estrogen receptor alpha; FADD: Fas-associated death domain; FSH: follicle- stimulating hormone; IL-1β: interleukin 1 beta; LH: luteinizing hormone; LPS: lipopolysaccharide; mFas: membrane Fas; MMP2: matrix metalloproteinase-2; MTA1: metastasis-associated protein 1; NAC: N-acetylcysteine; NCCD: the Nomenclature Committee on Cell Death; NFAT: nuclear factor of activated T-cells; NF-kB: nuclear transcription factor-kappaB; NO: nitric oxide; NP: 4-nonylphenol; PCD: programmed cell death; PP1/PP2A: protein phosphatase 1 and 2A; ROS: reactive oxygen species; sFas: soluble Fas; T: testosterone; TGF-β: transforming growth factor-beta; THD: TNF homology domain; TIMP-2: tissue inhibitor of

Agriculture Supplies & Services. Volume 3 of 3.

ERIC Educational Resources Information Center

Kansas State Univ., Manhattan.

The third of three volumes included in a secondary agricultural supplies and services curriculum guide, this volume contains twenty-five units of instruction in the area of agricultural mechanics. Among the unit topics included are (1) Farm Safety, (2) Ignition Systems; (3) Servicing Wheel Bearings, (4) Oxyacetylene Cutting, (5) Servicing the…

7 CFR 1484.21 - How does FAS determine which Cooperator program applications are approved?

Code of Federal Regulations, 2011 CFR

2011-01-01

... PROGRAMS TO HELP DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Application and Fund Allocation... allocates funds in a manner that effectively supports the strategic decision-making initiatives of the... to the effective creation, expansion, or maintenance of foreign markets, FAS seeks to identify those...

7 CFR 1484.21 - How does FAS determine which Cooperator program applications are approved?

Code of Federal Regulations, 2010 CFR

2010-01-01

... PROGRAMS TO HELP DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Application and Fund Allocation... allocates funds in a manner that effectively supports the strategic decision-making initiatives of the... to the effective creation, expansion, or maintenance of foreign markets, FAS seeks to identify those...

A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas.

PubMed

Villa-Morales, María; Santos, Javier; Pérez-Gómez, Eduardo; Quintanilla, Miguel; Fernández-Piqueras, José

2007-06-01

The Fas/FasL system mediates induced apoptosis of immature thymocytes and peripheral T lymphocytes, but little is known about its implication in genetic susceptibility to T-cell malignancies. In this article, we report that the expression of FasL increases early in all mice after gamma-radiation treatments, maintaining such high levels for a long time in mice that resisted tumor induction. However, its expression is practically absent in T-cell lymphoblastic lymphomas. Interestingly, there exist significant differences in the level of expression between two mice strains exhibiting extremely distinct susceptibilities that can be attributed to promoter functional polymorphisms. In addition, several functional nucleotide changes in the coding sequences of both Fas and FasL genes significantly affect their biological activity. These results lead us to propose that germ-line functional polymorphisms affecting either the levels of expression or the biological activity of both Fas and FasL genes could be contributing to the genetic risk to develop T-cell lymphoblastic lymphomas and support the use of radiotherapy as an adequate procedure to choose in the treatment of T-cell malignancies.

FAS system deregulation in T-cell lymphoblastic lymphoma

PubMed Central

Villa-Morales, M; Cobos, M A; González-Gugel, E; Álvarez-Iglesias, V; Martínez, B; Piris, M A; Carracedo, A; Benítez, J; Fernández-Piqueras, J

2014-01-01

The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations. PMID:24603338

7 CFR 2.79 - Administrator, Agricultural Marketing Service.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 1 2014-01-01 2014-01-01 false Administrator, Agricultural Marketing Service. 2.79... for Marketing and Regulatory Programs § 2.79 Administrator, Agricultural Marketing Service. (a... following delegations of authority are made by the Under Secretary for Marketing and Regulatory Programs to...

7 CFR 2.79 - Administrator, Agricultural Marketing Service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false Administrator, Agricultural Marketing Service. 2.79... for Marketing and Regulatory Programs § 2.79 Administrator, Agricultural Marketing Service. (a... following delegations of authority are made by the Under Secretary for Marketing and Regulatory Programs to...

7 CFR 2.79 - Administrator, Agricultural Marketing Service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Administrator, Agricultural Marketing Service. 2.79... for Marketing and Regulatory Programs § 2.79 Administrator, Agricultural Marketing Service. (a... following delegations of authority are made by the Under Secretary for Marketing and Regulatory Programs to...

7 CFR 2.79 - Administrator, Agricultural Marketing Service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 1 2011-01-01 2011-01-01 false Administrator, Agricultural Marketing Service. 2.79... for Marketing and Regulatory Programs § 2.79 Administrator, Agricultural Marketing Service. (a... following delegations of authority are made by the Under Secretary for Marketing and Regulatory Programs to...

Designing agricultural landscapes for biodiversity-based ecosystem services

DOE PAGES

Landis, Douglas A.

2016-07-28

Sustainable and resilient agricultural systems are needed to feed and fuel a growing human population. However, the current model of agricultural intensification which produces high yields has also resulted in a loss of biodiversity, ecological function, and critical ecosystem services in agricultural landscapes. A key consequence of agricultural intensification is landscape simplification, where once heterogeneous landscapes contain increasingly fewer crop and non-crop habitats. Landscape simplification exacerbates biodiversity losses which leads to reductions in ecosystem services on which agriculture depends. In recent decades, considerable research has focused on mitigating these negative impacts, primarily via management of habitats to promote biodiversity andmore » enhance services at the local scale. While it is well known that local and landscape factors interact, modifying overall landscape structure is seldom considered due to logistical constraints. Here, I propose that the loss of ecosystem services due to landscape simplification can only be addressed by a concerted effort to fundamentally redesign agricultural landscapes. Designing agricultural landscapes will require that scientists work with stakeholders to determine the mix of desired ecosystem services, evaluate current landscape structure in light of those goals, and implement targeted modifications to achieve them. I evaluate the current status of landscape design, ranging from fundamental ecological principles to resulting guidelines and socioeconomic tools. Finally, while research gaps remain, the time is right for ecologists to engage with other disciplines, stakeholders, and policymakers in education and advocacy to foster agricultural landscape design for sustainable and resilient biodiversity services.« less

Designing agricultural landscapes for biodiversity-based ecosystem services

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landis, Douglas A.

Sustainable and resilient agricultural systems are needed to feed and fuel a growing human population. However, the current model of agricultural intensification which produces high yields has also resulted in a loss of biodiversity, ecological function, and critical ecosystem services in agricultural landscapes. A key consequence of agricultural intensification is landscape simplification, where once heterogeneous landscapes contain increasingly fewer crop and non-crop habitats. Landscape simplification exacerbates biodiversity losses which leads to reductions in ecosystem services on which agriculture depends. In recent decades, considerable research has focused on mitigating these negative impacts, primarily via management of habitats to promote biodiversity andmore » enhance services at the local scale. While it is well known that local and landscape factors interact, modifying overall landscape structure is seldom considered due to logistical constraints. Here, I propose that the loss of ecosystem services due to landscape simplification can only be addressed by a concerted effort to fundamentally redesign agricultural landscapes. Designing agricultural landscapes will require that scientists work with stakeholders to determine the mix of desired ecosystem services, evaluate current landscape structure in light of those goals, and implement targeted modifications to achieve them. I evaluate the current status of landscape design, ranging from fundamental ecological principles to resulting guidelines and socioeconomic tools. Finally, while research gaps remain, the time is right for ecologists to engage with other disciplines, stakeholders, and policymakers in education and advocacy to foster agricultural landscape design for sustainable and resilient biodiversity services.« less

A new version of the HBSC Family Affluence Scale - FAS III: Scottish Qualitative Findings from the International FAS Development Study.

PubMed

Hartley, Jane E K; Levin, Kate; Currie, Candace

A critical review of the Family Affluence Scale (FAS) concluded that FAS II was no longer discriminatory within very rich or very poor countries, where a very high or a very low proportion of children were categorised as high FAS or low FAS respectively (Currie et al. 2008). The review concluded that a new version of FAS - FAS III - should be developed to take into account current trends in family consumption patterns across the European region, the US and Canada. In 2012, the FAS Development and Validation Study was conducted in eight countries - Denmark, Greenland, Italy, Norway, Poland, Romania, Slovakia and Scotland. This paper describes the Scottish qualitative findings from this study. The Scottish qualitative fieldwork comprising cognitive interviews and focus groups sampled from 11, 13 and 15 year-old participants from 18 of the most- and least- economically deprived schools. These qualitative results were used to inform the final FAS III recommendations.

7 CFR 1520.6 - Other information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... found on the FAS web site, www.fas.usda.gov. Also, the FAS annual FOIA report is available on the agency's web site at www.fas.usda.gov. Click on FOIA at the bottom of the page. To request a paper copy of the FAS FOAI annual report, write to: Foreign Agricultural Service, U.S. Department of Agriculture...

Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin

PubMed Central

García-Santos, G; Martin, V; Rodríguez-Blanco, J; Herrera, F; Casado-Zapico, S; Sánchez-Sánchez, A M; Antolín, I; Rodríguez, C

2012-01-01

Background: Despite recent advances in cancer therapy, the 5-year survival rate for Ewing's sarcoma is still very low, and new therapeutic approaches are necessary. It was found previously that melatonin induces cell death in the Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic pathway. Methods: Melatonin actions were analysed by metabolic viability/survival cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein activation/expression and electrophoretic mobility shift assay for transcription factor activation. Results: Melatonin increases the expression of Fas and its ligand Fas L, this increase being responsible for cell death induced by the indolamine. Melatonin also produces a transient increase in intracellular oxidants and activation of the redox-regulated transcription factor Nuclear factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell lines studied, and do not occur in the other tumour cell lines studied where melatonin does not induce cell death. Conclusion: Our data offers new insights in the study of alternative therapeutic strategies in the treatment of Ewing's sarcoma. Further attention deserves to be given to the differences in the cellular biology of sensitive tumours that could explain the cytotoxic effect of melatonin and the increase in the level of free radicals caused by this molecule, in particular cancer types. PMID:22382690

Lead induces apoptosis in mouse TM3 Leydig cells through the Fas/FasL death receptor pathway.

PubMed

He, Xiuyuan; Wu, Jing; Yuan, Liyun; Lin, Feng; Yi, Jine; Li, Jing; Yuan, Hui; Shi, Jinling; Yuan, Tingting; Zhang, Shufang; Fan, Yongheng; Zhao, Zhihang

2017-12-01

The study was aimed to investigate the effect of Pb toxicity on mouse Leydig cells and its molecular mechanism. The TM3 cells were cultured in vitro and exposed to Pb at different concentrations for 24h. The effects of Pb on cell proliferation and apoptosis were analyzed with MTT and Annexin V-FITC/PI via flow cytometry, respectively. Expression levels of Fas, Fas-L and caspase-8 in TM3 cells were determined by western blot. As well as the inhibitory effect of the caspase-8 inhibitor Z-IETD-FMK on cell apoptosis. We found that Pb treatment significantly decreased the cellar viability (P<0.05), increased the apoptosis (P<0.01) and the Fas, FasL, and caspase-8 expression levels in Pb-treated cells as compared to the control cells (P<0.05 or P<0.01). Furthermore, the caspase-8 inhibitor effectively block the Pb-induced cell apoptosis. Taken together, our data suggest that Pb-induced TM3 cell toxic effect may involve in the Fas/FasL death receptor signaling pathway. Copyright © 2017. Published by Elsevier B.V.

Comparative review of multifunctionality and ecosystem services in sustainable agriculture.

PubMed

Huang, Jiao; Tichit, Muriel; Poulot, Monique; Darly, Ségolène; Li, Shuangcheng; Petit, Caroline; Aubry, Christine

2015-02-01

Two scientific communities with broad interest in sustainable agriculture independently focus on multifunctional agriculture or ecosystem services. These communities have limited interaction and exchange, and each group faces research challenges according to independently operating paradigms. This paper presents a comparative review of published research in multifunctional agriculture and ecosystem services. The motivation for this work is to improve communication, integrate experimental approaches, and propose areas of consensus and dialog for the two communities. This extensive analysis of publication trends, ideologies, and approaches enables formulation of four main conclusions. First, the two communities are closely related through their use of the term "function." However, multifunctional agriculture considers functions as agricultural activity outputs and prefers farm-centred approaches, whereas ecosystem services considers ecosystem functions in the provision of services and prefers service-centred approaches. Second, research approaches to common questions in these two communities share some similarities, and there would be great value in integrating these approaches. Third, the two communities have potential for dialog regarding the bundle of ecosystem services and the spectrum of multifunctional agriculture, or regarding land sharing and land sparing. Fourth, we propose an integrated conceptual framework that distinguishes six groups of ecosystem services and disservices in the agricultural landscape, and combines the concepts of multifunctional agriculture and ecosystem services. This integrated framework improves applications of multifunctional agriculture and ecosystem services for operational use. Future research should examine if the framework can be readily adapted for modelling specific problems in agricultural management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Involvement of the Fas and Fas ligand in testicular germ cell apoptosis by zearalenone in rat

PubMed Central

Jee, Youngheun; Noh, Eun-Mi; Cho, Eun-Sang

2010-01-01

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is known to cause testicular toxicity in animals. In the present study, the effects of ZEA on spermatogenesis and possible mechanisms involved in germ cell injury were examined in rats. Ten-week-old Sprague-Dawley rats were treated with 5 mg/kg i.p. of ZEA and euthanized 3, 6, 12, 24 or 48 h after treatment. Histopathologically, spermatogonia and spermatocytes were found to be affected selectively. They were TUNEL-positive and found to be primarily in spermatogenic stages I-VI tubules from 6 h after dosing, increasing gradually until 12 h and then gradually decreasing. Western blot analysis revealed an increase in Fas and Fas ligand (Fas-L) protein levels in the ZEA-treated rats. However, the estrogen receptor (ER)α expression was not changed during the study. Collectively, our data suggest that acute exposure of ZEA induces apoptosis in germ cells of male rats and that this toxicity of ZEA is partially mediated through modulation of Fas and Fas-L systems, though ERα may not play a significant role. PMID:20458151

7 CFR 1599.1 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... by the Foreign Agricultural Service (FAS) of the U.S. Department of Agriculture (USDA) to... sale of such commodities, or funds provided by FAS to implement activities in a foreign country pursuant to an agreement with FAS. FAS administers the McGovern-Dole Program and acts on behalf of the...

7 CFR 1599.1 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... by the Foreign Agricultural Service (FAS) of the U.S. Department of Agriculture (USDA) to... sale of such commodities, or funds provided by FAS to implement activities in a foreign country pursuant to an agreement with FAS. FAS administers the McGovern-Dole Program and acts on behalf of the...

7 CFR 1599.1 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... by the Foreign Agricultural Service (FAS) of the U.S. Department of Agriculture (USDA) to... sale of such commodities, or funds provided by FAS to implement activities in a foreign country pursuant to an agreement with FAS. FAS administers the McGovern-Dole Program and acts on behalf of the...

7 CFR 1599.1 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... by the Foreign Agricultural Service (FAS) of the U.S. Department of Agriculture (USDA) to... sale of such commodities, or funds provided by FAS to implement activities in a foreign country pursuant to an agreement with FAS. FAS administers the McGovern-Dole Program and acts on behalf of the...

7 CFR 1599.1 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... by the Foreign Agricultural Service (FAS) of the U.S. Department of Agriculture (USDA) to... sale of such commodities, or funds provided by FAS to implement activities in a foreign country pursuant to an agreement with FAS. FAS administers the McGovern-Dole Program and acts on behalf of the...

Agricultural Research Service: biodefense research.

PubMed

Gay, C G

2013-01-01

The National Animal Health Program at the Agricultural Research Service (ARS), United States Department of Agriculture (USDA), includes research programs dedicated to the defense of animal agriculture against the treat of biological agents with the potential of significant economic harm and/or public health consequences. This article provides a summary of the program and identifies its relevance to national initiatives to protect livestock and poultry as well as global food security. An introduction to setting research priorities and a selection of research accomplishments that define the scope of the biodefense research program is provided.

Relationship between expression of gastrin, somatostatin, Fas/FasL and caspases in large intestinal carcinoma.

PubMed

Mao, Jia-Ding; Wu, Pei; Yang, Ying-Lin; Wu, Jian; Huang, He

2008-05-14

To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC). Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs = 0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes' stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 +/- 2.38 vs 7.82 +/- 2.38, P < 0.01; 5.51 +/- 2.66 vs 7.82 +/- 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 +/- 1.76 vs 5.35 +/- 3.00, P < 0.01; 7.44 +/- 2.67 vs 5.35 +/- 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (r(s) = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative

75 FR 59684 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS), denied a petition (No. 2011021) for trade adjustment assistance for wool filed under the... Office of the Chief Economist, Farm Service Agency, Agricultural Marketing Service, and FAS. After a... Programs, FAS, USDA, or by phone at (202) 720-0638, or (202) 690-0633, or by e-mail at: [email protected]fas...

miR-20a Regulates FAS Expression in Osteosarcoma Cells by Modulating FAS Promoter Activity and Can be Therapeutically Targeted to Inhibit Lung Metastases.

PubMed

Yang, Yuanzheng; Huang, Gangxiong; Zhou, Zhichao; Fewell, Jason G; Kleinerman, Eugenie S

2018-01-01

The metastatic potential of osteosarcoma cells is inversely correlated to cell surface FAS expression. Downregulation of FAS allows osteosarcoma cells to escape FAS ligand-mediated apoptosis when they enter a FAS ligand-positive microenvironment such as the lung. We have previously demonstrated that miR-20a, encoded by the miR-17-92 cluster, downregulates FAS expression in osteosarcoma. We further demonstrated an inverse correlation between FAS expression and miR-20a expression. However, the mechanism of FAS regulation by miR-20a was still unclear. The purpose of the current study was to evaluate the mechanism of FAS regulation by miR-20a in vitro and test the effect of targeting miR-20a in vivo We investigated whether miR-20a's downregulation of FAS was mediated by binding to the 3'-untranslated region (3'-UTR) of FAS mRNA with the consequent induction of mRNA degradation or translational suppression. We identified and mutated two miR-20a binding sites on the FAS mRNA 3'-UTR. Using luciferase reporter assays, we demonstrated that miR-20a did not bind to either the wild-type or mutated FAS 3'-UTR. In contrast, overexpression of miR-20a resulted in downregulation of FAS promoter activity. Similarly, the inhibition of miR-20a increased FAS promoter activity. The critical region identified on the FAS promoter was between -240 bp and -150 bp. Delivery of anti-miR-20a in vivo using nanoparticles in mice with established osteosarcoma lung metastases resulted in upregulation of FAS and tumor growth inhibition. Taken together, our data suggest that miR-20a regulates FAS expression through the modulation of the FAS promoter and that targeting miR-20a using anti-miR-20a has therapeutic potential. Mol Cancer Ther; 17(1); 130-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Association of the Polymorphisms in the Fas/FasL Promoter Regions with Cancer Susceptibility: A Systematic Review and Meta-Analysis of 52 Studies

PubMed Central

Pan, Yuqin; Gao, Tianyi; Deng, Qiwen; Sun, Huiling; Song, Guoqi; Wang, Shukui

2014-01-01

Fas and its ligand (FasL) play an important role in apoptosis and carcinogenesis. Therefore, the potential association of polymorphisms in the Fas (-670A>G, rs1800682; -1377G>A, rs2234767) and FasL (-844C>T, rs763110) with cancer risk has been widely investigated. However, all the currently available results are not always consistent. In this work, we performed a meta-analysis to further determine whether carriers of the polymorphisms in Fas and FasL of interest could confer an altered susceptibility to cancer. All relevant data were retrieved by PubMed and Web of Science, and 52 eligible studies were chosen for this meta-analysis. There was no association of the Fas -670A>G polymorphism with cancer risk in the pooled data. For the Fas -1377G>A and FasL -844C>T polymorphisms, results revealed that the homozygotes of -1377A and -844C were associated with elevated risk of cancer as a whole. Further stratified analysis indicated markedly increased risk for developing breast cancer, gastric cancer, and esophageal cancer, in particular in Asian population. We conclude that carriers of the Fas-1377A and the FasL -844C are more susceptible to the majority of cancers than non-carriers. PMID:24598538

Agricultural Census 2012: Publishing Mashable GIS Big Data Services

NASA Astrophysics Data System (ADS)

Mueller, R.

2014-12-01

The 2012 Agricultural Census was released by the US Department of Agriculture (USDA) on May 2nd 2014; published on a quinquennial basis covering all facets of American production agriculture. The Agricultural Census is a comprehensive source of uniform published agricultural data for every state and county in the US. This is the first Agricultural Census that is disseminated with web mapping services using REST APIs. USDA developed an open GIS mashable web portal that depicts over 250 maps on Crops and Plants, Economics, Farms, Livestock and Animals, and Operators. These mapping services written in JavaScript replace the traditional static maps published as the Ag Atlas. Web users can now visualize, interact, query, and download the Agricultural Census data in a means not previously discoverable. Stakeholders will now be able to leverage this data for activities such as community planning, agribusiness location suitability analytics, availability of loans/funds, service center locations and staffing, and farm programs and policies. Additional sites serving compatible mashable USDA Big Data web services are as follows: The Food Environment Atlas, The Atlas of Rural and Small-Town America, The Farm Program Atlas, SNAP Data System, CropScape, and VegScape. All portals use a similar data organization scheme of "Categories" and "Maps" providing interactive mashable web services for agricultural stakeholders to exploit.

Blockade of Fas Signaling in Breast Cancer Cells Suppresses Tumor Growth and Metastasis via Disruption of Fas Signaling-initiated Cancer-related Inflammation*

PubMed Central

Liu, Qiuyan; Tan, Qinchun; Zheng, Yuanyuan; Chen, Kun; Qian, Cheng; Li, Nan; Wang, Qingqing; Cao, Xuetao

2014-01-01

Mechanisms for cancer-related inflammation remain to be fully elucidated. Non-apoptotic functions of Fas signaling have been proposed to play an important role in promoting tumor progression. It has yet to be determined if targeting Fas signaling can control tumor progression through suppression of cancer-related inflammation. In the current study we found that breast cancer cells with constitutive Fas expression were resistant to apoptosis induction by agonistic anti-Fas antibody (Jo2) ligation or Fas ligand cross-linking. Higher expression of Fas in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. To determine whether blockade of Fas signaling in breast cancer could suppress tumor progression, we prepared an orthotopic xenograft mouse model with mammary cancer cells 4T1 and found that blockade of Fas signaling in 4T1 cancer cells markedly reduced tumor growth, inhibited tumor metastasis in vivo, and prolonged survival of tumor-bearing mice. Mechanistically, blockade of Fas signaling in cancer cells significantly decreased systemic or local recruitment of myeloid derived suppressor cells (MDSCs) in vivo. Furthermore, blockade of Fas signaling markedly reduced IL-6, prostaglandin E2 production from breast cancer cells by impairing p-p38, and activity of the NFκB pathway. In addition, administration of a COX-2 inhibitor and anti-IL-6 antibody significantly reduced MDSC accumulation in vivo. Therefore, blockade of Fas signaling can suppress breast cancer progression by inhibiting proinflammatory cytokine production and MDSC accumulation, indicating that Fas signaling-initiated cancer-related inflammation in breast cancer cells may be a potential target for treatment of breast cancer. PMID:24627480

Fetal alcohol syndrome (FAS) primary prevention through fas diagnosis: II. A comprehensive profile of 80 birth mothers of children with FAS.

PubMed

Astley, S J; Bailey, D; Talbot, C; Clarren, S K

2000-01-01

A 5-year, fetal alcohol syndrome (FAS) primary prevention study was conducted in Washington State to: (1) assess the feasibility of using a FAS diagnostic and prevention clinic as a centre for identifying and targeting primary prevention intervention to high-risk women; (2) generate a comprehensive, lifetime profile of these women; (3) identify factors that have enhanced and/or hindered their ability to achieve abstinence. The results of this study are presented in two parts. Objective 1 is summarized in the preceding paper and objectives 2 and 3 are summarized here. Comprehensive interviews were conducted with 80 women, who had given birth to a child diagnosed with FAS, to document their sociodemographics, reproductive and family planning history, social and healthcare utilization patterns, adverse social experiences, social support network, alcohol use and treatment history, mental health, and intelligence quotient (IQ). These high-risk women were diverse in racial, educational and economic backgrounds, were often victims of abuse, and challenged by mental health issues. Despite their rather harsh psychosocial profile, many demonstrated the ability to overcome their alcohol dependence over time. Relative to the women who had not achieved abstinence, the women who had achieved abstinence had significantly higher IQs, higher household incomes, larger more satisfactory social support networks, were more likely to report a religious affiliation, and were more likely to be receiving mental health treatment for their mental health disorders. The rate of unintended pregnancies and alcohol-exposed pregnancies was substantial. Key barriers to achieving effective family planning were maternal alcohol and drug use, lack of access to birth control and lack of support by their partner to use birth control. A FAS diagnostic and prevention clinic can be used to identify women at high risk for producing children damaged by prenatal alcohol exposure. Primary prevention programmes

7 CFR 2.68 - Administrator, National Agricultural Statistics Service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Administrator, National Agricultural Statistics... Statistics Service. (a) Delegations. Pursuant to § 2.21 (a)(3) and (a)(8), subject to reservations in § 2.21..., Education, and Economics to the Administrator, National Agricultural Statistics Service: (1) Prepare crop...

75 FR 59682 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS) has denied petitions (No.'s 2011006-2011011, 2011028) for trade adjustment assistance for..., Farm Service Agency, Agricultural Marketing Service, and FAS. After a review, the Administrator... Adjustment Assistance for Farmers Program Staff, Office of Trade Programs, FAS, USDA; or by phone at (202...

Melatonin partially protects 661W cells from H2O2-induced death by inhibiting Fas/FasL-caspase-3.

PubMed

Sánchez-Bretaño, Aída; Baba, Kenkichi; Janjua, Uzair; Piano, Ilaria; Gargini, Claudia; Tosini, Gianluca

2017-01-01

Previous studies have shown that melatonin (MEL) signaling is involved in the modulation of photoreceptor viability during aging. Recent work by our laboratory suggested that MEL may protect cones by modulating the Fas/FasL-caspase-3 pathway. In this study, we first investigated the presence of MEL receptors (MT 1 and MT 2 ) in 661W cells, then whether MEL can prevent H 2 O 2 -induced cell death, and last, through which pathway MEL confers protection. The mRNA and proteins of the MEL receptors were detected with quantitative PCR (q-PCR) and immunocytochemistry, respectively. To test the protective effect of MEL, 661W cells were treated with H 2 O 2 for 2 h in the presence or absence of MEL, a MEL agonist, and an antagonist. To study the pathways involved in H 2 O 2 -mediated cell death, a Fas/FasL antagonist was used before the exposure to H 2 O 2 . Finally, Fas/FasL and caspase-3 mRNA was analyzed with q-PCR and immunocytochemistry in cells treated with H 2 O 2 and/or MEL. Cell viability was analyzed by using Trypan Blue. Both MEL receptors (MT 1 and MT 2 ) were detected at the mRNA and protein levels in 661W cells. MEL partially prevented H 2 O 2 -mediated cell death (20-25%). This effect was replicated with IIK7 (a melatonin receptor agonist) when used at a concentration of 1 µM. Preincubation with luzindole (a melatonin receptor antagonist) blocked MEL protection. Kp7-6, an antagonist of Fas/FasL, blocked cell death caused by H 2 O 2 similarly to what was observed for MEL. Fas, FasL, and caspase-3 expression was increased in cells treated with H 2 O 2 , and this effect was prevented by MEL. Finally, MEL treatment partially prevented the activation of caspase-3 caused by H 2 O 2 . The results demonstrate that MEL receptors are present and functional in 661W cells. MEL can prevent photoreceptor cell death induced by H 2 O 2 via the inhibition of the proapoptotic pathway Fas/FasL-caspase-3.

The Cytocidal Activity of OK‐432‐activated Mononuclear Cells against Human Glioma Cells is Partly Mediated through the Fas Ligand/Fas System

PubMed Central

Toda, Keisuke; Shiraishi, Tetsuya; Hirotsu, Tatsumi; Fukuyama, Kouzou; Mineta, Toshihiro; Kawaguchi, Shojiro; Tabuchi, Kazuo

1996-01-01

We have been applying an adoptive immunotherapy protocol to patients with malignant brain tumors using OK‐432‐activated peripheral blood mononuclear cells (OK‐MCs). In order to elucidate the mechanism of OK‐MCs' cytotoxicity, we examined the expression of Fas ligand mRNA in OK‐MCs and the cytocidal activity of these cells against a human glioma cell line, T98G which expresses a high level of Fas. The expression of Fas ligand mRNA was low in non‐treated peripheral blood mononuclear cells and was elevated by treatment with OK‐432, irrespective of the dose employed. Apoptosis of T98G cells induced by OK‐MCs was unequivocally inhibited by the pretreatment of T98G cells with ZB4 monoclonal antibody, which binds to Fas and blocks the binding of Fas ligand to Fas. These data indicate that the cytotoxic activity of OK‐MCs via apoptosis seems to be at least partly mediated by the Fas ligand/Fas system. Adoptive immunotherapy using the Fas ligand/Fas system could be a new treatment modality for human malignant brain tumors. PMID:8878461

Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes.

PubMed

Jaita, Gabriela; Zárate, Sandra; Ferrari, Luciana; Radl, Daniela; Ferraris, Jimena; Eijo, Guadalupe; Zaldivar, Verónica; Pisera, Daniel; Seilicovich, Adriana

2011-02-01

We have previously reported that Fas activation induces apoptosis of anterior pituitary cells from rats at proestrus but not at diestrus and in an estrogen-dependent manner. In this study, we evaluated the effect of Fas activation on apoptosis of lactotropes and somatotropes during the estrous cycle and explored the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether changes in Fas expression are involved in the apoptotic response of anterior pituitary cells. Fas activation increased the percentage of TUNEL-positive lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered apoptosis of somatotropes only when cells from ovariectomized rats were cultured in the presence of 17 β-estradiol (E2). Progesterone (P4) blocked the apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the cell membrane. Our results show that Fas activation induces apoptosis of lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids may be involved in the apoptotic response of lactotropes and somatotropes, suggesting that Fas activation is implicated in the renewal of these pituitary subpopulations during the estrous cycle. The effect of gonadal steroids on Fas expression may be only partially involved in regulation of the Fas/FasL apoptotic pathway in the anterior pituitary gland.

TNFα sensitizes neuroblastoma cells to FasL-, cisplatin- and etoposide-induced cell death by NF-κB-mediated expression of Fas.

PubMed

Galenkamp, Koen Mo; Carriba, Paulina; Urresti, Jorge; Planells-Ferrer, Laura; Coccia, Elena; Lopez-Soriano, Joaquín; Barneda-Zahonero, Bruna; Moubarak, Rana S; Segura, Miguel F; Comella, Joan X

2015-03-19

Patients with high-risk neuroblastoma (NBL) tumors have a high mortality rate. Consequently, there is an urgent need for the development of new treatments for this condition. Targeting death receptor signaling has been proposed as an alternative to standard chemo- and radio-therapies in various tumors. In NBL, this therapeutic strategy has been largely disregarded, possibly because ~50-70% of all human NBLs are characterized by caspase-8 silencing. However, the expression of caspase-8 is detected in a significant group of NBL patients, and they could therefore benefit from treatments that induce cell death through death receptor activation. Given that cytokines, such as TNFα, are able to upregulate Fas expression, we sought to address the therapeutic relevance of co-treatment with TNFα and FasL in NBL. For the purpose of the study we used a set of eight NBL cell lines. Here we explore the cell death induced by TNFα, FasL, cisplatin, and etoposide, or a combination thereof by Hoechst staining and calcein viability assay. Further assessment of the signaling pathways involved was performed by caspase activity assays and Western blot experiments. Characterization of Fas expression levels was achieved by qRT-PCR, cell surface biotinylation assays, and cytometry. We have found that TNFα is able to increase FasL-induced cell death by a mechanism that involves the NF-κB-mediated induction of the Fas receptor. Moreover, TNFα sensitized NBL cells to DNA-damaging agents (i.e. cisplatin and etoposide) that induce the expression of FasL. Priming to FasL-, cisplatin-, and etoposide-induced cell death could only be achieved in NBLs that display TNFα-induced upregulation of Fas. Further analysis denotes that the high degree of heterogeneity between NBLs is also manifested in Fas expression and modulation thereof by TNFα. In summary, our findings reveal that TNFα sensitizes NBL cells to FasL-induced cell death by NF-κB-mediated upregulation of Fas and unveil a new

Transfer of Fas (CD95) protein from the cell surface to the surface of polystyrene beads coated with anti-Fas antibody clone CH-11

PubMed Central

Sawai, H.; Domae, N.

2010-01-01

Mouse monoclonal anti-Fas (CD95) antibody clone CH-11 has been widely used in research on apoptosis. CH-11 has the ability to bind to Fas protein on cell surface and induce apoptosis. Here, we used polystyrene beads coated with CH-11 to investigate the role of lipid rafts in Fas-mediated apoptosis in SKW6.4 cells. Unexpectedly, by treatment of the cells with CH-11-coated beads Fas protein was detached from cell surface and transferred to the surface of CH-11-coated beads. Western blot analysis showed that Fas protein containing both extracellular and intracellular domains was attached to the beads. Fas protein was not transferred from the cells to the surface of the beads coated with other anti-Fas antibodies or Fas ligand. Similar phenomenon was observed in Jurkat T cells. Furthermore, CH-11-induced apoptosis was suppressed by pretreatment with CH-11-coated beads in Jurkat cells. These results suggest that CH-11 might possess distinct properties on Fas protein compared with other anti-Fas antibodies or Fas ligand, and also suggest that caution should be needed to use polystyrene beads coated with antibodies such as CH-11. PMID:20353915

Identification of the Calmodulin-Binding Domains of Fas Death Receptor

PubMed Central

Chang, Bliss J.; Samal, Alexandra B.; Vlach, Jiri; Fernandez, Timothy F.; Brooke, Dewey; Prevelige, Peter E.; Saad, Jamil S.

2016-01-01

The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD) and that of the Fas-associated protein (FADD) interact to form the core of the death-inducing signaling complex (DISC), a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD). However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR), biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas–mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209–239 (Fas-Pep1) and 251–288 (Fas-Pep2) constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD–CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling

Fas-Fas ligand interactions are essential for the binding to and killing of activated macrophages by gamma delta T cells.

PubMed

Dalton, Jane E; Howell, Gareth; Pearson, Jayne; Scott, Phillip; Carding, Simon R

2004-09-15

Gammadelta T cells have a direct role in resolving the host immune response to infection by eliminating populations of activated macrophages. Macrophage reactivity resides within the Vgamma1/Vdelta6.3 subset of gammadelta T cells, which have the ability to kill activated macrophages following infection with Listeria monocytogenes (Lm). However, it is not known how gammadelta T cell macrophage cytocidal activity is regulated, or what effector mechanisms gammadelta T cells use to kill activated macrophages. Using a macrophage-T cell coculture system in which peritoneal macrophages from naive or Lm-infected TCRdelta-/- mice were incubated with splenocytes from wild-type and Fas ligand (FasL)-deficient mice (gld), the ability of Vgamma1 T cells to bind macrophages was shown to be dependent upon Fas-FasL interactions. Combinations of anti-TCR and FasL Abs completely abolished binding to and killing of activated macrophages by Vgamma1 T cells. In addition, confocal microscopy showed that Fas and the TCR colocalized on Vgamma1 T cells at points of contact with macrophages. Collectively, these studies identify an accessory or coreceptor-like function for Fas-FasL that is essential for the interaction of Vgamma1 T cells with activated macrophages and their elimination during the resolution stage of pathogen-induced immune responses. Copyright 2004 The American Association of Immunologists, Inc.

Fas/APO-1 (CD95) expression in myelodysplastic syndromes.

PubMed

Lepelley, P; Grardel, N; Erny, O; Iaru, T; Obein, V; Cosson, A; Fenaux, P

1998-07-01

Increased apoptosis of myeloid precursors appears to contribute to the pathophysiology of cytopenias in myelodysplastic syndromes (MDS). Fas /APO-1(CD95) is a cell surface protein inducing an apoptotic signal after its binding to Fas ligand or to a functional anti-Fas antibody. Here we studied Fas expression by immunocytochemistry on marrow slides from 30 cases of MDS. Increased Fas expression in erythroblasts and/or immature granulocytes, compared to controls, was seen in 12 (40%) of the cases. In addition, in 16 of the 18 cases with > or = 5% marrow blasts, a variable proportion of blasts expressed Fas. Increased apoptosis was found by morphological analysis and/or TUNEL technique in marrow cells from 8 of the 26 cases analyzed (31%) The ability of Fas antigen to trigger apoptosis was studied after addition of a functional anti Fas antibody in 5 of the patients with Fas overexpression. Addition of this antibody, however, only lead to mild increase of apoptosis in immature granulocytes (but not other myeloid cells) in 2 of the 5 cases. Thus, increased Fas expression is seen in myeloid and/or blast cells in the majority of MDS cases. However, the relationship between this finding and increased apoptosis in MDS still remains to be established.

Relationship between expression of gastrin, somatostatin, Fas/FasL and caspases in large intestinal carcinoma

PubMed Central

Mao, Jia-Ding; Wu, Pei; Yang, Ying-Lin; Wu, Jian; Huang, He

2008-01-01

AIM: To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC). METHODS: Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. RESULTS: There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs=0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes’ stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 ± 2.38 vs 7.82 ± 2.38, P < 0.01; 5.51 ± 2.66 vs 7.82 ± 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 ± 1.76 vs 5.35 ± 3.00, P < 0.01; 7.44 ± 2.67 vs 5.35 ± 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (rs = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the

75 FR 59682 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS) has denied petitions (Nos. 2011023-2011027) for trade adjustment assistance for wool filed... Economist, Farm Service Agency, Agricultural Marketing Service, and FAS. After a review, the Administrator... Adjustment Assistance for Farmers Program Staff, Office of Trade Programs, FAS, USDA; or by phone at (202...

Effects of celecoxib on cell apoptosis and Fas, FasL and Bcl-2 expression in a BGC-823 human gastric cancer cell line.

PubMed

Li, Qian; Peng, Jie; Liu, Ting; Zhang, Guiying

2017-09-01

Fas, which is an apoptotic-related protein, has an important role in cell apoptosis. Fas ligand (FasL) binds to Fas and activates apoptosis signal transduction. We previously demonstrated that the efficiency of celecoxib inhibited the proliferation and apoptosis of HT-29 colon cancer cell line. The BGC823 cell line was used as an experimental model to evaluate the potential role of celecoxib on gastric cancer cell apoptosis. Inhibitory effects of celecoxib on cell viability were determined by MTT assay. Cell apoptosis was evaluated by flow cytometric analysis and laser confocal microscopy. The results of the present study demonstrated that celecoxib inhibited the viability of BGC823 cells in a concentration- and time-dependent manner. Furthermore, the effect of BGC823 cells apoptosis was increased in a concentration-dependent manner. Western blotting was used to determine the protein expression levels of Fas, FasL, and B-cell lymphoma-2 (Bcl-2). During the celecoxib-induced apoptosis of BGC823 cells, celecoxib upregulated Fas expression and downregulated FasL and Bcl-2 expression in a concentration-dependent manner. These results suggest that celecoxib inhibited the growth and induced apoptosis of BGC823 gastric cancer cells by regulating the protein expression of Fas, FasL and Bcl-2.

Application of Terrestrial Microwave Remote Sensing to Agricultural Drought Monitoring

NASA Astrophysics Data System (ADS)

Crow, W. T.; Bolten, J. D.

2014-12-01

Root-zone soil moisture information is a valuable diagnostic for detecting the onset and severity of agricultural drought. Current attempts to globally monitor root-zone soil moisture are generally based on the application of soil water balance models driven by observed meteorological variables. Such systems, however, are prone to random error associated with: incorrect process model physics, poor parameter choices and noisy meteorological inputs. The presentation will describe attempts to remediate these sources of error via the assimilation of remotely-sensed surface soil moisture retrievals from satellite-based passive microwave sensors into a global soil water balance model. Results demonstrate the ability of satellite-based soil moisture retrieval products to significantly improve the global characterization of root-zone soil moisture - particularly in data-poor regions lacking adequate ground-based rain gage instrumentation. This success has lead to an on-going effort to implement an operational land data assimilation system at the United States Department of Agriculture's Foreign Agricultural Service (USDA FAS) to globally monitor variations in root-zone soil moisture availability via the integration of satellite-based precipitation and soil moisture information. Prospects for improving the performance of the USDA FAS system via the simultaneous assimilation of both passive and active-based soil moisture retrievals derived from the upcoming NASA Soil Moisture Active/Passive mission will also be discussed.

75 FR 59684 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS) has denied a petition (No. 2011001) for trade adjustment assistance for coffee filed under... of the Chief Economist, Farm Service Agency, Agricultural Marketing Service, and FAS. After a review... Adjustment Assistance for Farmers Program Staff, Office of Trade Programs, FAS, USDA; or by phone at (202...

75 FR 63437 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... Service (FAS) has denied a petition (No. 2011032) for trade adjustment assistance (TAA) for blueberries... USDA's Office of the Chief Economist, Farm Service Agency, Agricultural Marketing Service, and FAS..., Office of Trade Programs, FAS, USDA, at (202) 720-0638, or (202) 690-0633, or by e-mail at...

Prenatal Exposure of Mice to Diethylstilbestrol Disrupts T-Cell Differentiation by Regulating Fas/Fas Ligand Expression through Estrogen Receptor Element and Nuclear Factor-κB Motifs

PubMed Central

Singh, Narendra P.; Singh, Udai P.; Nagarkatti, Prakash S.

2012-01-01

Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions. PMID:22888145

Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs.

PubMed

Singh, Narendra P; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2012-11-01

Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions.

75 FR 59683 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS) has denied a petition (No. 2011020) for trade adjustment assistance for coffee filed under... of the Chief Economist, Farm Service Agency, Agricultural Marketing Service, and FAS. After a review... Trade Programs, FAS, USDA; or by phone at (202) 720-0638 or (202) 690-0633; or by e-mail at...

Trifluoperazine Regulation of Calmodulin Binding to Fas: A Computational Study

PubMed Central

Pan, Di; Yan, Qi; Chen, Yabing; McDonald, Jay M; Song, Yuhua

2011-01-01

Death-inducing signaling complex (DISC) formation is a critical step in Fas-mediated signaling for apoptosis. Previous experiments have demonstrated that the calmodulin (CaM) antagonist, trifluoperazine (TFP) regulates CaM-Fas binding and affects Fas-mediated DISC formation. In this study, we investigated the anti-cooperative characteristics of TFP binding to CaM and the effect of TFP on the CaM-Fas interaction from both structural and thermodynamic perspectives using combined molecular dynamics simulations and binding free energy analyses. We studied the interactions of different numbers of TFP molecules with CaM and explored the effects of the resulting conformational changes in CaM on CaM-Fas binding. Results from these analyses showed that the number of TFP molecules bound to CaM directly influenced α-helix formation and hydrogen bond occupancy within the α-helices of CaM, contributing to the conformational and motion changes in CaM. These changes affected CaM binding to Fas, resulting in secondary structural changes in Fas and conformational and motion changes of Fas in CaM-Fas complexes, potentially perturbing the recruitment of Fas-associated death domain (FADD) for DISC formation. The computational results from this study reveal the structural and molecular mechanisms that underlie the role of the CaM antagonist, TFP, in regulation of CaM-Fas binding and Fas-mediated DISC formation in a concentration-dependent manner. PMID:21656570

Ecosystem Services from Edible Insects in Agricultural Systems: A Review.

PubMed

Payne, Charlotte L R; Van Itterbeeck, Joost

2017-02-17

Many of the most nutritionally and economically important edible insects are those that are harvested from existing agricultural systems. Current strategies of agricultural intensification focus predominantly on increasing crop yields, with no or little consideration of the repercussions this may have for the additional harvest and ecology of accompanying food insects. Yet such insects provide many valuable ecosystem services, and their sustainable management could be crucial to ensuring future food security. This review considers the multiple ecosystem services provided by edible insects in existing agricultural systems worldwide. Directly and indirectly, edible insects contribute to all four categories of ecosystem services as outlined by the Millennium Ecosystem Services definition: provisioning, regulating, maintaining, and cultural services. They are also responsible for ecosystem disservices, most notably significant crop damage. We argue that it is crucial for decision-makers to evaluate the costs and benefits of the presence of food insects in agricultural systems. We recommend that a key priority for further research is the quantification of the economic and environmental contribution of services and disservices from edible insects in agricultural systems.

Ecosystem Services from Edible Insects in Agricultural Systems: A Review

PubMed Central

Payne, Charlotte L. R.; Van Itterbeeck, Joost

2017-01-01

Many of the most nutritionally and economically important edible insects are those that are harvested from existing agricultural systems. Current strategies of agricultural intensification focus predominantly on increasing crop yields, with no or little consideration of the repercussions this may have for the additional harvest and ecology of accompanying food insects. Yet such insects provide many valuable ecosystem services, and their sustainable management could be crucial to ensuring future food security. This review considers the multiple ecosystem services provided by edible insects in existing agricultural systems worldwide. Directly and indirectly, edible insects contribute to all four categories of ecosystem services as outlined by the Millennium Ecosystem Services definition: provisioning, regulating, maintaining, and cultural services. They are also responsible for ecosystem disservices, most notably significant crop damage. We argue that it is crucial for decision-makers to evaluate the costs and benefits of the presence of food insects in agricultural systems. We recommend that a key priority for further research is the quantification of the economic and environmental contribution of services and disservices from edible insects in agricultural systems. PMID:28218635

Fas Binding to Calmodulin Regulates Apoptosis in Osteoclasts*

PubMed Central

Wu, Xiaojun; Ahn, Eun-Young; McKenna, Margaret A.; Yeo, Hyeonju; McDonald, Jay M.

2005-01-01

Promotion of osteoclast apoptosis is one therapeutic approach to osteoporosis. Calmodulin, the major intracellular Ca2+ receptor, modulates both osteoclastogenesis and bone resorption. The calmodulin antagonist, trifluoperazine, rescues bone loss in ovariectomized mice (Zhang, L., Feng, X., and McDonald, J. M. (2003) Endocrinology 144, 4536–4543). We show here that a 3-h treatment of mouse osteoclasts with either of the calmodulin antagonists, tamoxifen or trifluoperazine, induces osteoclast apoptosis dose-dependently. Tamoxifen, 10 μm, and trifluoperazine, 10 μm, induce 7.3 ± 1.8-fold and 5.3 ± 0.9-fold increases in osteoclast apoptosis, respectively. In Jurkat cells, calmodulin binds to Fas, the death receptor, and this binding is regulated during Fas-mediated apoptosis (Ahn, E. Y., Lim, S. T., Cook, W. J., and McDonald, J. M. (2004) J. Biol. Chem. 279, 5661–5666). In osteoclasts, calmodulin also binds Fas. When osteoclasts are treated with 10 μm trifluoperazine, the binding between Fas and calmodulin is dramatically decreased at 15 min and gradually recovers by 60 min. A point mutation of the Fas death domain in the Lpr−cg mouse renders Fas inactive. Using glutathione S-transferase fusion proteins, the human Fas cytoplasmic domain is shown to bind calmodulin, whereas a point mutation (V254N) comparable with the Lpr−cg mutation in mice has markedly reduced calmodulin binding. Osteoclasts derived from Lpr−cg mice have diminished calmodulin/Fas binding and are more sensitive to calmodulin antagonist-induced apoptosis than those from wild-type mice. Both tamoxifen- and trifluoperazine-induced apoptosis are increased 1.6 ± 0.2-fold in Lpr−cg-derived osteoclasts compared with osteoclasts derived from wild-type mice. In summary, calmodulin antagonists induce apoptosis in osteoclasts by a mechanism involving interference with calmodulin binding to Fas. The effects of calmodulin/Fas binding on calmodulin antagonist-induced apoptosis may open a new

CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface fas ligand expression and amplifies fas-mediated hepatocyte death during allograft rejection.

PubMed

Afford, S C; Randhawa, S; Eliopoulos, A G; Hubscher, S G; Young, L S; Adams, D H

1999-01-18

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68(+) macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved.

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

PubMed

Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M

2001-12-01

Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

75 FR 59682 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Service (FAS) has denied a petition (No. 2011005) for trade adjustment assistance for wool filed under the... of the Chief Economist, Farm Service Agency, Agricultural Marketing Service, and FAS. After a review..., Office of Trade Programs, FAS, USDA, or by phone at (202) 720-0638 or (202) 690-0633, or by e-mail at...

Agricultural industries transportation services (AITS) statewide needs assessment study : agriculture worker transportation needs assessment

DOT National Transportation Integrated Search

2003-05-01

The California Department of Transportation (Caltrans) funded the Agricultural Industries Transportation Services Statewide Needs Assessment Study to determine the existence and extent of the unmet transportation needs among the state's agricultural ...

FasL-triggered death of Jurkat cells requires caspase 8-induced, ATP-dependent cross-talk between Fas and the purinergic receptor P2X(7).

PubMed

Aguirre, Adam; Shoji, Kenji F; Sáez, Juan C; Henríquez, Mauricio; Quest, Andrew F G

2013-02-01

Fas ligation via the ligand FasL activates the caspase-8/caspase-3-dependent extrinsic death pathway. In so-called type II cells, an additional mechanism involving tBid-mediated caspase-9 activation is required to efficiently trigger cell death. Other pathways linking FasL-Fas interaction to activation of the intrinsic cell death pathway remain unknown. However, ATP release and subsequent activation of purinergic P2X(7) receptors (P2X(7)Rs) favors cell death in some cells. Here, we evaluated the possibility that ATP release downstream of caspase-8 via pannexin1 hemichannels (Panx1 HCs) and subsequent activation of P2X(7)Rs participate in FasL-stimulated cell death. Indeed, upon FasL stimulation, ATP was released from Jurkat cells in a time- and caspase-8-dependent manner. Fas and Panx1 HCs colocalized and inhibition of the latter, but not connexin hemichannels, reduced FasL-induced ATP release. Extracellular apyrase, which hydrolyzes ATP, reduced FasL-induced death. Also, oxidized-ATP or Brilliant Blue G, two P2X(7)R blockers, reduced FasL-induced caspase-9 activation and cell death. These results represent the first evidence indicating that the two death receptors, Fas and P2X(7)R connect functionally via caspase-8 and Panx1 HC-mediated ATP release to promote caspase-9/caspase-3-dependent cell death in lymphoid cells. Thus, a hitherto unsuspected route was uncovered connecting the extrinsic to the intrinsic pathway to amplify death signals emanating from the Fas receptor in type II cells. Copyright © 2012 Wiley Periodicals, Inc.

Multifunctional Agriculture: Conducting an Ecosystem Service Assessment for an Agricultural Watershed

NASA Astrophysics Data System (ADS)

Wacha, K.; Papanicolaou, T.; Wilson, C. G.

2012-12-01

To meet the food production demands on a finite area of land for an exponentially growing, global population, intensive agricultural management practices are being used. The implications of this these practices lead to soil degradation, loss of biodiversity, increased greenhouse gas emissions, and decreased water quality depending on the level of conservation practices implemented in a watershed. To offset these negative environmental effects, ecosystem services should be analyzed for possible economic valuation to provide incentives for good land stewardship. In this study a Multifunctional Agriculture (MFA) evaluation in a representative agricultural watershed in Iowa was performed by assessing the ecosystem services of water quality, crop/grain production, carbon sequestration, reduction in carbon dioxide emissions and biodiversity for representative land covers (e.g., corn-soybean rotation, alfalfa, oats, and Conservation Reserve Program, or CRP). The services were analyzed using a geo-spatial platform that simulated carbon dynamics with the biogeochemical model, CENTURY, as well as soil erosion/deposition and surface runoff with the Water Erosion Prediction Project (WEPP). Economic values given to the various services were based on current grain prices, water treatment costs, and hypothetical carbon storage credits. Results showed that crop/grain production for the corn-soybean rotations provided the largest service for the study site, followed by alfalfa. CRP provided the largest decrease in surface water runoff and CO2 emissions, while alfalfa provided the largest form of plant species diversity. The largest sequestration of carbon came from the corn-soybean rotation due to large amounts dead plant material being incorporated into the soil through tillage. Overall the MFA assessment can provide a framework for payment of ecosystem services supplied by agroecosystems which promote more sustainable land management practices.

Characterization of Calmodulin–Fas Death Domain Interaction: An Integrated Experimental and Computational Study

PubMed Central

2015-01-01

The Fas death receptor-activated death-inducing signaling complex (DISC) regulates apoptosis in many normal and cancer cells. Qualitative biochemical experiments demonstrate that calmodulin (CaM) binds to the death domain of Fas. The interaction between CaM and Fas regulates Fas-mediated DISC formation. A quantitative understanding of the interaction between CaM and Fas is important for the optimal design of antagonists for CaM or Fas to regulate the CaM–Fas interaction, thus modulating Fas-mediated DISC formation and apoptosis. The V254N mutation of the Fas death domain (Fas DD) is analogous to an identified mutant allele of Fas in lpr-cg mice that have a deficiency in Fas-mediated apoptosis. In this study, the interactions of CaM with the Fas DD wild type (Fas DD WT) and with the Fas DD V254N mutant were characterized using isothermal titration calorimetry (ITC), circular dichroism spectroscopy (CD), and molecular dynamics (MD) simulations. ITC results reveal an endothermic binding characteristic and an entropy-driven interaction of CaM with Fas DD WT or with Fas DD V254N. The Fas DD V254N mutation decreased the association constant (Ka) for CaM–Fas DD binding from (1.79 ± 0.20) × 106 to (0.88 ± 0.14) × 106 M–1 and slightly increased a standard state Gibbs free energy (ΔG°) for CaM–Fas DD binding from −8.87 ± 0.07 to −8.43 ± 0.10 kcal/mol. CD secondary structure analysis and MD simulation results did not show significant secondary structural changes of the Fas DD caused by the V254N mutation. The conformational and dynamical motion analyses, the analyses of hydrogen bond formation within the CaM binding region, the contact numbers of each residue, and the electrostatic potential for the CaM binding region based on MD simulations demonstrated changes caused by the Fas DD V254N mutation. These changes caused by the Fas DD V254N mutation could affect the van der Waals interactions and electrostatic interactions between CaM and Fas DD, thereby

GloFAS-Seasonal: Operational Seasonal Ensemble River Flow Forecasts at the Global Scale

NASA Astrophysics Data System (ADS)

Emerton, Rebecca; Zsoter, Ervin; Smith, Paul; Salamon, Peter

2017-04-01

Seasonal hydrological forecasting has potential benefits for many sectors, including agriculture, water resources management and humanitarian aid. At present, no global scale seasonal hydrological forecasting system exists operationally; although smaller scale systems have begun to emerge around the globe over the past decade, a system providing consistent global scale seasonal forecasts would be of great benefit in regions where no other forecasting system exists, and to organisations operating at the global scale, such as disaster relief. We present here a new operational global ensemble seasonal hydrological forecast, currently under development at ECMWF as part of the Global Flood Awareness System (GloFAS). The proposed system, which builds upon the current version of GloFAS, takes the long-range forecasts from the ECMWF System4 ensemble seasonal forecast system (which incorporates the HTESSEL land surface scheme) and uses this runoff as input to the Lisflood routing model, producing a seasonal river flow forecast out to 4 months lead time, for the global river network. The seasonal forecasts will be evaluated using the global river discharge reanalysis, and observations where available, to determine the potential value of the forecasts across the globe. The seasonal forecasts will be presented as a new layer in the GloFAS interface, which will provide a global map of river catchments, indicating whether the catchment-averaged discharge forecast is showing abnormally high or low flows during the 4-month lead time. Each catchment will display the corresponding forecast as an ensemble hydrograph of the weekly-averaged discharge forecast out to 4 months, with percentile thresholds shown for comparison with the discharge climatology. The forecast visualisation is based on a combination of the current medium-range GloFAS forecasts and the operational EFAS (European Flood Awareness System) seasonal outlook, and aims to effectively communicate the nature of a seasonal

Modules in Agricultural Education for Agricultural Supplies and Services.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Occupational and Career Curriculum Development.

Each of the 22 curriculum modules in this packet for instruction in agricultural supplies and services contains a brief description of the module content, a list of the major division or units, the overall objectives, objectives by units, content outline, and suggested teaching methods, student application activities, and evaluation procedures. A…

7 CFR 2.68 - Administrator, National Agricultural Statistics Service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... committees concerned with agricultural science, education, and development activities, including library and... Under Secretary for Research, Education, and Economics § 2.68 Administrator, National Agricultural..., Education, and Economics to the Administrator, National Agricultural Statistics Service: (1) Prepare crop...

7 CFR 2.68 - Administrator, National Agricultural Statistics Service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... committees concerned with agricultural science, education, and development activities, including library and... Under Secretary for Research, Education, and Economics § 2.68 Administrator, National Agricultural..., Education, and Economics to the Administrator, National Agricultural Statistics Service: (1) Prepare crop...

Low Doses of Exogenous Interferon-γ Attenuated Airway Inflammation Through Enhancing Fas/FasL-Induced CD4+ T Cell Apoptosis in a Mouse Asthma Model

PubMed Central

Yao, Yinan; Lu, Shan; Lu, Guohua

2012-01-01

To investigate whether low doses of exogenous interferon (IFN)-γ attenuate airway inflammation, and the underlying mechanisms, in asthma. C57BL/6 mice (n=42), after intraperitoneal ovalbumin (OVA) sensitization on day 0 and day 12, were challenged with OVA aerosol for 6 consecutive days. Different doses of IFN-γ were then administered intraperitoneally 5 min before each inhalation during OVA challenge. Airway hyperresponsiveness, airway inflammatory cells, cytokine profiles, and Fas/FasL expression on CD4+ T cells were evaluated in an asthma model. The effect of various IFN-γ doses on Fas/FasL expression and CD4+ T cell apoptosis were assessed in vitro. We demonstrated that low doses of IFN-γ reduced pulmonary infiltration of inflammatory cells, Th2 cytokine production, and goblet cells hyperplasia (P<0.05), while high doses of endogenous IFN-γ had almost no effect. We also found that low doses of IFN-γ relocated Fas/FasL to the CD4+ T cell surface in the asthma model (P<0.05) and increased FasL-induced apoptosis in vitro (P<0.05). Furthermore, treatment with MFL-3, an anti-FasL antibody, partially abolished the anti- inflammatory properties of IFN-γ in the airway rather than affecting the Th1/Th2 balance. This research has revealed an alternative mechanism in asthma that involves low doses of IFN-γ, which attenuate airway inflammation through enhancing Fas/FasL-induced CD4+ T cell apoptosis. PMID:22994871

FAS grafted superhydrophobic ceramic membrane

NASA Astrophysics Data System (ADS)

Lu, Jun; Yu, Yun; Zhou, Jianer; Song, Lixin; Hu, Xingfang; Larbot, Andre

2009-08-01

The hydrophobic properties of γ-Al 2O 3 membrane have been obtained by grafting fluoroalkylsilane (FAS) on the surface of the membrane. The following grafting parameters were studied: the eroding time of the original membrane, the grafting time, the concentration of FAS solution and the multiplicity of grafting. Hydrophobicity of the membranes was characterized by contact angle (CA) measurement. The thermogravimetric analysis (TGA) was used to investigate the weight loss process (25-800 °C) of the fluoroalkylsilane grafted on Al 2O 3 powders under different grafting conditions. The morphologies of the membranes modified under different parameters were examined by field emission scanning electron microscopy (FE-SEM) and the surface roughness (Ra) was measured using white light interferometers. A needle-like structure was observed on the membrane surface after modification, which causes the change of Ra. On the results above, we speculated a model to describe the reaction between FAS and γ-Al 2O 3 membrane surface as well as the formed surface morphology.

Increased expression of Fas receptor and Fas ligand in the culture of the peripheral blood mononuclear cells stimulated with Borrelia burgdorferi sensu lato.

PubMed

Grygorczuk, Sambor; Osada, Joanna; Moniuszko, Anna; Świerzbińska, Renata; Kondrusik, Maciej; Zajkowska, Joanna; Dunaj, Justyna; Dąbrowska, Milena; Pancewicz, Sławomir

2015-03-01

Apoptosis of the lymphocytes plays an essential role in the regulation of inflammatory/immune responses and its abnormalities may contribute to a chronic infection, persistent inflammation and autoimmunity. Its role in the pathogenesis of the late Lyme borreliosis manifestations has not been studied so far. We have measured Th lymphocyte apoptosis rate, membrane expression of pro-apoptotic Fas receptor, and supernatant concentrations of selected soluble pro- and anti-apoptotic mediators in cultures of peripheral blood mononuclear cells from 16 patients with disseminated Lyme borreliosis (6 with osteoarticular symptoms, 7 with neuroborreliosis and 3 with acrodermatitis chronica atrophicans) and 8 healthy controls. The cultures stimulated for 48h with live Borrelia burgdorferi sensu stricto, B. garinii or B. afzelii spirochetes. Fraction of the apoptotic Th (CD3+CD4+) lymphocytes and expression of Fas in this cell population was measured cytometrically and concentrations of soluble Fas, soluble Fas ligand, IL-10, IL-12 and TGF-β in culture supernatant with ELISA assays. The expression of IL-10, soluble and membrane Fas and soluble Fas ligand was increased under stimulation and higher in the presence of B. burgdorferi sensu stricto than the other species. Apoptosis rate was not affected. There was no difference between Lyme borreliosis patients and controls. IL-10 concentration correlated negatively with the membrane Fas expression and apoptosis under stimulation with B. afzelii and B. garinii. Expression of Fas/FasL system is up-regulated under stimulation with B. burgdorferi, but without corresponding increase in lymphocyte apoptosis. Variable responses observed with different B. burgdorferi species may reflect differences in the pathogenesis of the infection in vivo. Copyright © 2014 Elsevier GmbH. All rights reserved.

Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells

PubMed Central

Matsuzawa, Akio; Shimizu, Motomu; Takeda, Yasutaka; Nagase, Hisashi; Sayama, Kazutoshi; Kimura, Mikio

2002-01-01

The functional differences between two mutations of the Fas (CD95) locus, Faslpr (lpr) and Faslprcg (lprcg), were investigated using bone marrow (BM) transplantation on the C3H mouse background. Both lpr/lpr and lprcg/lprcg BM transferred caused lymph node (LN) hyperplasia in lpr/+ and lprcg/+ recipients, although it was clearly smaller than that in lpr/lpr and lprcg/lprcg recipients of lpr/lpr and lprcg/lprcg BM. In addition, both BM induced significantly larger LN hyperplasia in lprcg/+ than lpr/+ recipients. Appearance of CD4− CD8−[double negative (DN)] T cells in the periphery is the most consistent phenotype of Fas mutations. Importantly, the proportion of DN T cells was higher in larger LN hyperplasia in the order of lpr/+, lprcg/+ and lpr/lpr or lprcg/lprcg recipients. On the other hand, both lpr/lpr and lprcg/lprcg BM transferred into wild-type (+/+) mice caused marked LN atrophy. The former, but not the latter, induced wasting syndrome. Faslg1d (gld)-homozygous lpr/lpr BM transferred into +/+ mice elicited LN hyperplasia of the same extent as that in lpr/lpr mice transferred with lpr/lpr BM, but not wasting syndrome. Taken together with the fact that DN T cells massively express Fas ligand (FasL), this study implied that FasL overexpressed on DN cells may be involved in the accumulation of DN T cells in LN, LN atrophy and wasting syndrome, and that lprcg Fas, which can bind to Fas ligand but not transduce apoptosis signal into cells, may modulate these pathological conditions by interfering with the binding of FasL to Fas. PMID:12153509

a Study on the Document Information Service of the National Agricultural Library for Agricultural Sci-Tech Innovation in China

NASA Astrophysics Data System (ADS)

Xu, Qian; Meng, Xianxue

This paper presents the significant function of the Chinese National Agricultural Library (CNAL) in the agricultural sci-tech innovation system in China, analyses the development of collection and service in the CNAL, explores the challenge towards sustain and develop information services for the agricultural sci-tech research and innovation, at last proposes the strategy for sci-tech document information service development.

7 CFR 1407.2 - Nonprocurement debarment and suspension.

Code of Federal Regulations, 2010 CFR

2010-01-01

... initiated on behalf of CCC by the Foreign Agricultural Service (FAS), the Food and Nutrition Service (FNS... President, CCC, who is the Administrator FAS, FNS, or AMS, respectively. For actions initiated on behalf of...

7 CFR 1407.2 - Nonprocurement debarment and suspension.

Code of Federal Regulations, 2011 CFR

2011-01-01

... initiated on behalf of CCC by the Foreign Agricultural Service (FAS), the Food and Nutrition Service (FNS... President, CCC, who is the Administrator FAS, FNS, or AMS, respectively. For actions initiated on behalf of...

7 CFR 1407.2 - Nonprocurement debarment and suspension.

Code of Federal Regulations, 2013 CFR

2013-01-01

... initiated on behalf of CCC by the Foreign Agricultural Service (FAS), the Food and Nutrition Service (FNS... President, CCC, who is the Administrator FAS, FNS, or AMS, respectively. For actions initiated on behalf of...

7 CFR 1407.2 - Nonprocurement debarment and suspension.

Code of Federal Regulations, 2012 CFR

2012-01-01

... initiated on behalf of CCC by the Foreign Agricultural Service (FAS), the Food and Nutrition Service (FNS... President, CCC, who is the Administrator FAS, FNS, or AMS, respectively. For actions initiated on behalf of...

7 CFR 1407.2 - Nonprocurement debarment and suspension.

Code of Federal Regulations, 2014 CFR

2014-01-01

... initiated on behalf of CCC by the Foreign Agricultural Service (FAS), the Food and Nutrition Service (FNS... President, CCC, who is the Administrator FAS, FNS, or AMS, respectively. For actions initiated on behalf of...

Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM): expression of Fas ligand/Fas-mediated apoptosis signaling molecules in luteal cells.

PubMed

Kiso, Minako; Manabe, Noboru; Komatsu, Kohji; Shimabe, Munetake; Miyamoto, Hajime

2003-12-01

Senescence accelerated mouse-prone (SAMP) mice with a shortened life span show accelerated changes in many of the signs of aging and a shorter reproductive life span than SAM-resistant (SAMR) controls. We previously showed that functional regression (progesterone dissimilation) occurs in abnormally accumulated luteal bodies (aaLBs) of SAMP mice, but structural regression of luteal cells in aaLB is inhibited. A deficiency of luteal cell apoptosis causes the abnormal accumulation of LBs in SAMP ovaries. In the present study, to show the abnormality of Fas ligand (FasL)/Fas-mediated apoptosis signal transducing factors in the aaLBs of the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase-8 and caspase-3 mRNAs by reverse transcription-polymerase chain reaction, and in the expression and localization of FasL, Fas and activated caspase-3 proteins by Western blotting and immunohistochemistry, respectively, during the estrus cycle/luteolysis. These mRNAs and proteins were expressed in normal LBs of both SAMP and SAMR ovaries, but not at all or only in trace amounts in aaLBs of SAMP, indicating that structural regression is inhibited by blockage of the expression of these transducing factors in luteal cells of aaLBs in SAMP mice.

78 FR 56648 - Notice of a Request for a Reinstatement of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Notice of a Request for a Reinstatement of a Currently Approved Information Collection AGENCY: Foreign Agricultural Service, USDA. ACTION... notice announces that the Foreign Agricultural Service (FAS) intends to reinstate a currently approved...

Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats.

PubMed

Liu, Yang; Liu, Xiuheng; Wang, Lei; Du, Yang; Chen, Zhiyuan; Chen, Hui; Guo, Jia; Weng, Xiaodong; Wang, Xiao; Wang, Ming; Wang, Zhishun

2017-12-01

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo . Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro . Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro . In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.

Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats

PubMed Central

Liu, Yang; Liu, Xiuheng; Wang, Lei; Du, Yang; Chen, Zhiyuan; Chen, Hui; Guo, Jia; Weng, Xiaodong; Wang, Xiao; Wang, Ming; Wang, Zhishun

2017-01-01

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo. Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro. Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro. In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats. PMID:29285062

Agriculture--Agricultural Sales and Service. Kit No. 21. Instructor's Manual [and] Student Learning Activity Guide.

ERIC Educational Resources Information Center

Caines, Royce

An instructor's manual and student activity guide on agricultural sales and service are provided in this set of prevocational education materials which focuses on the vocational area of agriculture. (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven vocational offerings: agriculture, home…

Stimulation of Fas/FasL-mediated apoptosis by luteolin through enhancement of histone H3 acetylation and c-Jun activation in HL-60 leukemia cells.

PubMed

Wang, Shih-Wei; Chen, Yun-Ru; Chow, Jyh-Ming; Chien, Ming-Hsien; Yang, Shun-Fa; Wen, Yu-Ching; Lee, Wei-Jiunn; Tseng, Tsui-Hwa

2018-07-01

Luteolin (3',4',5,7-tetrahydroxyflavone), which exists in fruits, vegetables, and medicinal herbs, is used in Chinese traditional medicine for treating various diseases, such as hypertension, inflammatory disorders, and cancer. However, the gene-regulatory role of luteolin in cancer prevention and therapy has not been clarified. Herein, we demonstrated that treatment with luteolin resulted in a significant decrease in the viability of human leukemia cells. In the present study, by evaluating fragmentation of DNA and poly (ADP-ribose) polymerase (PARP), we found that luteolin was able to induce PARP cleavage and nuclear fragmentation as well as an increase in the sub-G 0 /G 1 fraction. In addition, luteolin also induced Fas and Fas ligand (FasL) expressions and subsequent activation of caspases-8 and -3, which can trigger the extrinsic apoptosis pathway, while knocking down Fas-associated protein with death domain (FADD) prevented luteolin-induced PARP cleavage. Immunoblot and chromatin immunoprecipitation (ChIP) analyses revealed that luteolin increased acetylation of histone H3, which is involved in the upregulation of Fas and FasL. Moreover, both the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways are involved in luteolin-induced histone H3 acetylation. Finally, luteolin also activated the c-Jun signaling pathway, which contributes to FasL, but not Fas, gene expression and downregulation of c-Jun expression by small interfering RNA transfection which resulted in a significant decrease in luteolin-induced PARP cleavage. Thus, our results demonstrate that luteolin induced apoptosis of HL-60 cells, and this was associated with c-Jun activation and histone H3 acetylation-mediated Fas/FasL expressions. © 2018 Wiley Periodicals, Inc.

75 FR 41432 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Trade Adjustment Assistance for Farmers AGENCY: Foreign Agricultural Service, USDA. ACTION: Notice. The Administrator of the Foreign Agricultural Service (FAS) has denied a petition (No. 2010002) for trade adjustment assistance (TAA) for U.S. lobster...

78 FR 55238 - Notice of Request for New Approval of Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... Agricultural Service (FAS) intends to request the approval of a new information collection process involving... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Notice of Request for New Approval of Information Collection AGENCY: Foreign Agricultural Service, USDA. ACTION: Notice and request for comments...

76 FR 80329 - Notice of Request for Revision of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Notice of Request for Revision of a Currently Approved Information Collection AGENCY: Foreign Agricultural Service, USDA. ACTION: Notice and... announces that the Foreign Agricultural Service (FAS) intends to request a renewal and revision of a...

Mutation in the Fas Pathway Impairs CD8+ T Cell Memory1

PubMed Central

Dudani, Renu; Russell, Marsha; van Faassen, Henk; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Fas death pathway is important for lymphocyte homeostasis, but the role of Fas pathway in T cell memory development is not clear. We show that whereas the expansion and contraction of CD8+ T cell response against Listeria monocytogenes were similar for wild-type (WT) and Fas ligand (FasL) mutant mice, the majority of memory CD8+ T cells in FasL mutant mice displayed an effector memory phenotype in the long-term in comparison with the mainly central memory phenotype displayed by memory CD8+ T cells in WT mice. Memory CD8+ T cells in FasL mutant mice expressed reduced levels of IFN-γ and displayed poor homeostatic and Ag-induced proliferation. Impairment in CD8+ T cell memory in FasL mutant hosts was not due to defective programming or the expression of mutant FasL on CD8+ T cells, but was caused by perturbed cytokine environment in FasL mutant mice. Although adoptively transferred WT memory CD8+ T cells mediated protection against L. monocytogenes in either the WT or FasL mutant hosts, FasL mutant memory CD8+ T cells failed to mediate protection even in WT hosts. Thus, in individuals with mutation in Fas pathway, impairment in the function of the memory CD8+ T cells may increase their susceptibility to recurrent/latent infections. PMID:18292515

The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy.

PubMed

Kim, Ryungsa; Emi, Manabu; Tanabe, Kazuaki; Uchida, Yoko; Toge, Tetsuya

2004-06-01

Despite the fact that expression of Fas ligand (FasL) in cytotoxic T lymphocytes (CTLs) and in natural killer (NK) cells plays an important role in Fas-mediated tumor killing, During tumor progression FasL-expressing tumor cells are involved in counterattacking to kill tumor-infiltrating lymphocytes (TILs). Soluble FasL levels also increase with tumor progression in solid tumors, and this increase inhibits Fas-mediated tumor killing by CTLs and NK cells. The increased expression of FasL in tumor cells is associated with decreased expression of Fas; and the promoter region of the FASL gene is regulated by transcription factors, such as neuronal factor kappaB (NF-kappaB) and AP-1, in the tumor microenvironment. Although the ratio of FasL expression to Fas expression in tumor cells is not strongly related to the induction of apoptosis in TILs, increased expression of FasL is associated with decreased Fas levels in tumor cells that can escape immune surveillance and facilitate tumor progression and metastasis. Transforming growth factor beta (TGF-beta) is a potent growth inhibitor and has tumor-suppressing activity in the early phases of carcinogenesis. During subsequent tumor progression, the increased secretion of TGF-beta by both tumor cells and, in a paracrine fashion, stromal cells, is involved in the enhancement of tumor invasion and metastasis accompanied by immunosuppression. Herein, the authors review the clinical significance of FasL and TGF-beta expression patterns as features of immune privilege accompanying tumor progression in the tumor microenvironment. Potential strategies for identifying which molecules can serve as targets for effective antitumor therapy also are discussed. Copyright 2004 American Cancer Society.

Course of Study in Agricultural Occupations (Agricultural-Supply Businesses--Sales and Service) for Reidland High School, Department of Vocational Agriculture.

ERIC Educational Resources Information Center

Binkley, Harold

This high school agricultural occupations teacher's guide was developed as part of a pilot program and tested at Reidland High School. The course objective is to develop skills and understandings needed in agricultural supply sales and service. Units are (1) Opportunities in Agricultural Occupations, (2) Orientation to the Training Program, (3)…

Fluoride reduced the immune privileged function of mouse Sertoli cells via the regulation of Fas/FasL system.

PubMed

Sun, Zilong; Nie, Qingli; Zhang, Lianjie; Niu, Ruiyan; Wang, Jundong; Wang, Shaolin

2017-02-01

Previous investigations have demonstrated the adverse impacts of fluoride on Sertoli cells (SCs), such as oxidative stress and apoptosis. SCs are the crucial cellular components that can create the immune privileged environment in testis. However, the effect of fluoride on SCs immune privilege is unknown. In this study, mouse SCs were exposed to sodium fluoride with varying concentrations of 10 -5 , 10 -4 , and 10 -3  mol/L to establish the model of fluoride-treated SCs (F-SCs) in vitro. After 48 h of incubation, F-SCs were transplanted underneath the kidney capsule of mice for 21 days, or cocultured with spleen lymphocytes for another 48 h. Immunohistochemical analysis of GATA4 in SCs grafts underneath kidney capsule presented less SCs distribution and obvious immune cell infiltration in F-SCs groups. In addition, the levels of FasL protein and mRNA in non-cocultured F-SCs decreased with the increase of fluoride concentration. When cocultured with F-SCs, lymphocytes presented significantly high cell viability and low apoptosis in F-SCs groups. Protein and mRNA expressions of FasL in cocultured F-SCs and Fas in lymphocytes were reduced, and the caspase 8 and caspase 3 mRNA levels were also decreased in fluoride groups in a dose-dependent manner. These findings indicated that fluoride influenced the testicular immune privilege through disturbing the Fas/FasL system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Agricultural Supplies and Services. Program Planning Guide: Volume 2.

ERIC Educational Resources Information Center

Welton, Richard; Marks, Michael

The program planning guide for agricultural supplies and services was written to assist Applied Biological and Agricultural Occupations (ABAO) teachers in enriching existing programs and/or to provide the basis for expansion of offerings to include additional materials for the cluster areas of agricultural chemicals, feeds, seeds, fertilizers, and…

Crosstalk between Fas and JNK determines lymphocyte apoptosis after ionizing radiation.

PubMed

Praveen, Koganti; Saxena, Nandita

2013-06-01

Radiation simultaneously activate Fas and JNK pathway in lymphocytes but their precise interaction is not clearly understood. Activation of Fas pathway is required for radiation induced apoptosis, however induction of JNK pathway may or may not contribute in apoptosis. Here we report that Fas, Fas associated death domain and total JNK are activated in a dose- and time-dependent radiation exposure. A biphasic pattern of phospho-JNK was found at lower doses (1 and 2 Gy), however at higher doses of radiation phospho-JNK was continuously activated. Interestingly, Fas ligand expression remained biphasic at all the doses of radiation. Our results suggest that the Fas pathway is the major player in radiation-induced apoptosis, with JNK playing a contributory role. We also observed that Fas ligand expression by radiation is dependent on JNK activation. We also propose that radiation activates JNK pathway, but sustained activation is required for maximal induction of apoptosis at later times. Our findings define a mechanism for crosstalk between JNK and Fas pathway in radiation-induced apoptosis, which may lead to the development of new therapeutic strategies.

75 FR 28780 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-24

... Service (FAS) will begin accepting Trade Adjustment Assistance (TAA) for Farmers petitions for Fiscal Year... July 16, 2010. They may use form FAS-930 for this purpose. Petitions may be sent by fax: (202) 720-0876; or by e-mail: [email protected]fas.usda.gov ; or by U.S. mail: TAA, Foreign Agricultural Service, Stop...

FAS promoter polymorphisms and serum sFas level are associated with increased risk of nerve damage in Bangladeshi patients with Guillain-Barré syndrome.

PubMed

Islam, Zhahirul; Jahan, Israt; Ahammad, Rijwan U; Shahnaij, Mohammad; Nahar, Shamsun; Mohammad, Quazi D

2018-01-01

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population. Genotype distributions were not significantly different between patients with GBS and healthy controls. The FAS -670 AG heterozygous (P = 0.0005, OR = 2.5, 95% CI = 1.5-4.2) and GG homozygous (P = 0.0048, OR = 2.6, 95% CI = 1.3-5.0) genotypes were more common in patients with anti-GM1 antibodies than patients without anti-GM1 antibodies. The FAS -670 G allele was more prevalent in anti-GM1 antibody-positive than -negative patients (P = 0.0002, OR = 1.9, 95% CI = 1.4-2.7) and also in patients with the axonal subtype than demyelinating subtype (P < 0.0001, OR = 4.8, 95% CI = 2.3-10.1). The 1377G/-670G GG haplotype was significantly associated with the axonal subtype (P < 0.0001) and anti-ganglioside antibody-positivity (P = 0.0008) in GBS. Serum sFas (237.5 pg/mL vs. 159.5 pg/mL; P < 0.0001) and sFasL (225.1 pg/mL vs. 183.4 pg/mL; P = 0.0069) were elevated in patients with GBS compared to healthy controls, and among patients with high serum sFas was associated with severe GBS (P = 0.0406). In conclusion, this study indicates FAS-FASL promoter SNPs may promote the production of cross-reactive anti-ganglioside antibodies in GBS.

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas-Fas ligand and mitochondrial pathway.

PubMed

Liu, Pei-Ying; Chang, Dun-Cheng; Lo, Yu-Sheng; Hsi, Yi-Ting; Lin, Chia-Chieh; Chuang, Yi-Ching; Lin, Shu-Hui; Hsieh, Ming-Ju; Chen, Mu-Kuan

2018-04-01

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC. © 2018 Wiley Periodicals, Inc.

Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli.

PubMed

Dodi, Amos E; Ajayi, Iyabode O; Chang, Christine; Beard, Meghan; Ashley, Shanna L; Huang, Steven K; Thannickal, Victor J; Tschumperlin, Daniel J; Sisson, Thomas H; Horowitz, Jeffrey C

2018-05-10

Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when Fas (CD95) expression is increased in these cells. Moreover, prior work shows that Fas expression in fibrotic lung fibroblasts is reduced by epigenetic silencing of the Fas promoter. However, the mechanisms by which microenvironmental stimuli such as TGF-β1 and substrate stiffness affect fibroblast Fas expression are not well understood. Primary normal human lung fibroblasts (IMR-90) were cultured on tissue culture plastic or on polyacrylamide hydrogels with Young's moduli to recapitulate the compliance of normal (400 Pa) or fibrotic (6400 Pa) lung tissue and treated with or without TGF-β1 (10 ng/mL) in the presence or absence of protein kinase inhibitors and/or inflammatory cytokines. Expression of Fas was assessed by quantitative real time RT-PCR, ELISA and Western blotting. Soluble Fas (sFas) was measured in conditioned media by ELISA. Apoptosis was assessed using the Cell Death Detection Kit and by Western blotting for cleaved PARP. Fas expression and susceptibility to apoptosis was diminished in fibroblasts cultured on 6400 Pa substrates compared to 400 Pa substrates. TGF-β1 reduced Fas mRNA and protein in a time- and dose-dependent manner dependent on focal adhesion kinase (FAK). Surprisingly, TGF-β1 did not significantly alter cell-surface Fas expression, but did stimulate secretion of sFas. Finally, enhanced Fas expression and increased susceptibility to apoptosis was induced by combined treatment with TNF-α/IFN-γ and was not inhibited by TGF-β1. Soluble and matrix-mediated pro-fibrotic stimuli promote fibroblast resistance to apoptosis by decreasing Fas transcription while stimulating soluble

Severe necroinflammatory reaction caused by natural killer cell-mediated Fas/Fas ligand interaction and dendritic cells in human hepatocyte chimeric mouse.

PubMed

Okazaki, Akihito; Hiraga, Nobuhiko; Imamura, Michio; Hayes, C Nelson; Tsuge, Masataka; Takahashi, Shoichi; Aikata, Hiroshi; Abe, Hiromi; Miki, Daiki; Ochi, Hidenori; Tateno, Chise; Yoshizato, Katsutoshi; Ohdan, Hideki; Chayama, Kazuaki

2012-08-01

The necroinflammatory reaction plays a central role in hepatitis B virus (HBV) elimination. Cluster of differentiation (CD)8-positive cytotoxic T lymphocytes (CTLs) are thought to be a main player in the elimination of infected cells, and a recent report suggests that natural killer (NK) cells also play an important role. Here, we demonstrate the elimination of HBV-infected hepatocytes by NK cells and dendritic cells (DCs) using urokinase-type plasminogen activator/severe combined immunodeficiency mice, in which the livers were highly repopulated with human hepatocytes. After establishing HBV infection, we injected human peripheral blood mononuclear cells (PBMCs) into the mice and analyzed liver pathology and infiltrating human immune cells with flow cytometry. Severe hepatocyte degeneration was observed only in HBV-infected mice transplanted with human PBMCs. We provide the first direct evidence that massive liver cell death can be caused by Fas/Fas ligand (FasL) interaction provided by NK cells activated by DCs. Treatment of mice with anti-Fas antibody completely prevented severe hepatocyte degeneration. Furthermore, severe hepatocyte death can be prevented by depletion of DCs, whereas depletion of CD8-positive CTLs did not disturb the development of massive liver cell apoptosis. Our findings provide the first direct evidence that DC-activated NK cells induce massive HBV-infected hepatocyte degeneration through the Fas/FasL system and may indicate new therapeutic implications for acute severe/fulminant hepatitis B. Copyright © 2012 American Association for the Study of Liver Diseases.

7 CFR 2.43 - Administrator, Foreign Agricultural Service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Department under the Defense Production Act of 1950, as amended (50 U.S.C. App. 2061 et seq.), and title VI... OF AGRICULTURE AND GENERAL OFFICERS OF THE DEPARTMENT Delegations of Authority by the Under Secretary... Administrator, Foreign Agricultural Service: (1) Coordinate the carrying out by Department agencies of their...

7 CFR 2.43 - Administrator, Foreign Agricultural Service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Department under the Defense Production Act of 1950, as amended (50 U.S.C. App. 2061 et seq.), and title VI... OF AGRICULTURE AND GENERAL OFFICERS OF THE DEPARTMENT Delegations of Authority by the Under Secretary... Administrator, Foreign Agricultural Service: (1) Coordinate the carrying out by Department agencies of their...

7 CFR 2.43 - Administrator, Foreign Agricultural Service.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Department under the Defense Production Act of 1950, as amended (50 U.S.C. App. 2061 et seq.), and title VI... OF AGRICULTURE AND GENERAL OFFICERS OF THE DEPARTMENT Delegations of Authority by the Under Secretary... Administrator, Foreign Agricultural Service: (1) Coordinate the carrying out by Department agencies of their...

7 CFR 2.43 - Administrator, Foreign Agricultural Service.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Department under the Defense Production Act of 1950, as amended (50 U.S.C. App. 2061 et seq.), and title VI... OF AGRICULTURE AND GENERAL OFFICERS OF THE DEPARTMENT Delegations of Authority by the Under Secretary... Administrator, Foreign Agricultural Service: (1) Coordinate the carrying out by Department agencies of their...

Methotrexate Induces Apoptosis in Organ-Cultured Nasal Polyps Via the Fas Pathway.

PubMed

Heo, Kyung Wook; Park, Seong Kook; Lee, Yeo Myeong; Choe, Si Hong; Gu, Pyung Mo; Hong, Tae Ui; Hur, Dae Young

2017-05-01

Methotrexate (MTX) is very effective when used to treat chronic inflammatory diseases, and also induces apoptosis in nasal polyps (NPs). Increasing evidence suggests that Fas-Fas ligand (FasL) interactions activate multiple pathways involved in the regulation of immune and inflammatory cell functions. The aim of the present study was to identify pathways activated by Fas signaling when NPs were treated with MTX. Nasal polyps tissues were cultured using an air-liquid interface organ culture method. Cultures were maintained in the absence or presence of MTX (10 or 100 μM) for 24 hours. The authors used the reverse transcription-polymerase chain reaction method and Western blotting to identify pathways activated by Fas when NPs were treated with MTX. The Fas mRNA expression ratio was unchanged upon MTX treatment, but the FasL mRNA expression ratio was significantly higher in MTX-treated than nontreated polyps. In addition, the expression levels of the Fas and FasL proteins were significantly higher in polyps treated with both 10 and 100 μM MTX compared with nontreated polyps. Methotrexate induces apoptosis in NPs via the Fas pathway. Future studies should explore the topical use of MTX for NP control. Methotrexate may be a useful alternative steroid-sparing agent for the treatment of NPs.

Fas/APO-1 protein is increased in spaceflown lymphocytes (Jurkat)

NASA Technical Reports Server (NTRS)

Cubano, L. A.; Lewis, M. L.

2000-01-01

Human lymphocytes flown on the Space Shuttle respond poorly to mitogen stimulation and populations of the lymphoblastoid T cell line, Jurkat, manifest growth arrest, increase in apoptosis and time- and microgravity-dependent increases in the soluble form of the cell death factor, Fas/APO-1 (sFas). The potential role of apoptosis in population dynamics of space-flown lymphocytes has not been investigated previously. We flew Jurkat cells on Space Transportation System (STS)-80 and STS-95 to determine whether apoptosis and the apparent microgravity-related release of sFas are characteristic of lymphocytes in microgravity. The effects of spaceflight and ground-based tests simulating spaceflight experimental conditions, including high cell density and low serum concentration, were assessed. Immunofluorescence microscopy showed increased cell associated Fas in flown cells. Results of STS-80 and STS-95 confirmed increase in apoptosis during spaceflight and the release of sFas as a repeatable, time-dependent and microgravity-related response. Ground-based tests showed that holding cells at 1.5 million/ml in medium containing 2% serum before launch did not increase sFas. Reports of increased Fas in cells of the elderly and the increases in spaceflown cells suggest possible similarities between aging and spaceflight effects on lymphocytes.

Functional traits in agriculture: agrobiodiversity and ecosystem services.

PubMed

Wood, Stephen A; Karp, Daniel S; DeClerck, Fabrice; Kremen, Claire; Naeem, Shahid; Palm, Cheryl A

2015-09-01

Functional trait research has led to greater understanding of the impacts of biodiversity in ecosystems. Yet, functional trait approaches have not been widely applied to agroecosystems and understanding of the importance of agrobiodiversity remains limited to a few ecosystem processes and services. To improve this understanding, we argue here for a functional trait approach to agroecology that adopts recent advances in trait research for multitrophic and spatially heterogeneous ecosystems. We suggest that trait values should be measured across environmental conditions and agricultural management regimes to predict how ecosystem services vary with farm practices and environment. This knowledge should be used to develop management strategies that can be easily implemented by farmers to manage agriculture to provide multiple ecosystem services. Copyright © 2015 Elsevier Ltd. All rights reserved.

Farming for Ecosystem Services: An Ecological Approach to Production Agriculture

PubMed Central

Philip Robertson, G.; Gross, Katherine L.; Hamilton, Stephen K.; Landis, Douglas A.; Schmidt, Thomas M.; Snapp, Sieglinde S.; Swinton, Scott M.

2014-01-01

A balanced assessment of ecosystem services provided by agriculture requires a systems-level socioecological understanding of related management practices at local to landscape scales. The results from 25 years of observation and experimentation at the Kellogg Biological Station long-term ecological research site reveal services that could be provided by intensive row-crop ecosystems. In addition to high yields, farms could be readily managed to contribute clean water, biocontrol and other biodiversity benefits, climate stabilization, and long-term soil fertility, thereby helping meet society's need for agriculture that is economically and environmentally sustainable. Midwest farmers—especially those with large farms—appear willing to adopt practices that deliver these services in exchange for payments scaled to management complexity and farmstead benefit. Surveyed citizens appear willing to pay farmers for the delivery of specific services, such as cleaner lakes. A new farming for services paradigm in US agriculture seems feasible and could be environmentally significant. PMID:26955069

Farming for Ecosystem Services: An Ecological Approach to Production Agriculture.

PubMed

Philip Robertson, G; Gross, Katherine L; Hamilton, Stephen K; Landis, Douglas A; Schmidt, Thomas M; Snapp, Sieglinde S; Swinton, Scott M

2014-05-01

A balanced assessment of ecosystem services provided by agriculture requires a systems-level socioecological understanding of related management practices at local to landscape scales. The results from 25 years of observation and experimentation at the Kellogg Biological Station long-term ecological research site reveal services that could be provided by intensive row-crop ecosystems. In addition to high yields, farms could be readily managed to contribute clean water, biocontrol and other biodiversity benefits, climate stabilization, and long-term soil fertility, thereby helping meet society's need for agriculture that is economically and environmentally sustainable. Midwest farmers-especially those with large farms-appear willing to adopt practices that deliver these services in exchange for payments scaled to management complexity and farmstead benefit. Surveyed citizens appear willing to pay farmers for the delivery of specific services, such as cleaner lakes. A new farming for services paradigm in US agriculture seems feasible and could be environmentally significant.

Methotrexate inhibits the viability of human melanoma cell lines and enhances Fas/Fas-ligand expression, apoptosis and response to interferon-alpha: Rationale for its use in combination therapy

PubMed Central

Nihal, Minakshi; Wu, Jianqiang; Wood, Gary S.

2015-01-01

Melanoma, a highly aggressive form of cancer, is notoriously resistant to available therapies. Methotrexate (MTX), an antifolate, competitively inhibits DNA synthesis and is effective for several types of cancer. In cutaneous T-cell lymphoma (CTCL), MTX increases Fas death receptor by decreasing Fas promoter methylation by blocking the synthesis of SAM, the principal methyl donor for DNMTs, resulting in enhanced Fas-mediated apoptosis. The objective of this study was to explore the effects of MTX in human melanoma. MTX variably inhibited the survival of melanoma cells and induced apoptosis as evident by annexin V positivity and senescence associated β-galactosidase activity induction. Furthermore, MTX caused increased transcript and protein levels of extrinsic apoptotic pathway factors Fas and Fas-ligand, albeit at different levels in different cell lines. Our pyrosequencing studies showed that this increased expression of Fas was associated with Fas promoter demethylation. Overall, the ability of MTX to up-regulate Fas/FasL and enhance melanoma apoptosis through extrinsic as well as intrinsic pathways might make it a useful component of novel combination therapies designed to affect multiple melanoma targets simultaneously. In support of this concept, combination therapy with MTX and interferon-alpha (IFNα) induced significantly greater apoptosis in the aggressive A375 cell line than either agent alone. PMID:24862567

Long noncoding RNA Saf and splicing factor 45 increase soluble Fas and resistance to apoptosis

PubMed Central

Riberdy, Janice M.; Persons, Derek A.; Wilber, Andrew

2016-01-01

In multicellular organisms, cell growth and differentiation is controlled in part by programmed cell death or apoptosis. One major apoptotic pathway is triggered by Fas receptor (Fas)-Fas ligand (FasL) interaction. Neoplastic cells are frequently resistant to Fas-mediated apoptosis, evade Fas signals through down regulation of Fas and produce soluble Fas proteins that bind FasL thereby blocking apoptosis. Soluble Fas (sFas) is an alternative splice product of Fas pre-mRNA, commonly created by exclusion of transmembrane spanning sequences encoded within exon 6 (FasΔEx6). Long non-coding RNAs (lncRNAs) interact with other RNAs, DNA, and proteins to regulate gene expression. One lncRNA, Fas-antisense or Saf, was shown to participate in alternative splicing of Fas pre-mRNA through unknown mechanisms. We show that Saf is localized in the nucleus where it interacts with Fas receptor pre-mRNA and human splicing factor 45 (SPF45) to facilitate alternative splicing and exclusion of exon 6. The product is a soluble Fas protein that protects cells against FasL-induced apoptosis. Collectively, these studies reveal a novel mechanism to modulate this critical cell death program by an lncRNA and its protein partner. PMID:26885613

Distinct role of the Fas rs1800682 and FasL rs763110 polymorphisms in determining the risk of breast cancer among Han Chinese females.

PubMed

Wang, Meng; Wang, Zheng; Wang, Xi-Jing; Jin, Tian-Bo; Dai, Zhi-Ming; Kang, Hua-Feng; Guan, Hai-Tao; Ma, Xiao-Bin; Liu, Xing-Han; Dai, Zhi-Jun

2016-01-01

In recent years, studies have demonstrated that polymorphisms in the promoters of Fas and FasL are significantly associated with breast cancer risk. However, the results of these studies were inconsistent. This case-control study was performed to explore the associations between Fas rs1800682 and FasL rs763110 polymorphisms and breast cancer. A hospital-based case-control study of 560 Han Chinese females with breast cancer (583 controls) was conducted. The MassARRAY system was used to search for a possible association between the disease risk and the two single nucleotide polymorphisms, Fas rs1800682 and FasL rs763110. Statistical analyses were performed using SNPStats software to conduct Pearson's chi-square tests in five different genetic models. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjustment to age and body mass index. PHASE v2.1 software was used to reconstruct all common haplotypes. A statistically significant association was found between Fas rs1800682 and increased breast cancer risk (AG vs AA: OR =1.37, 95% CI =1.06-1.78; AA+AG vs GG: OR =1.32, 95% CI =1.04-1.66), and also it was found that the FasL rs763110 polymorphism may decrease the risk. Stratified analyses demonstrated that the rs763110 polymorphism was associated with lower breast cancer risk among postmenopausal females (heterozygote model: OR =0.69, 95% CI =0.49-0.97; dominant model: OR =0.70, 95% CI =0.51-0.96). The T allele of rs763110 was also associated with a decreased risk of lymph node metastasis (allele model: OR =0.75, 95% CI =0.57-0.97) and an increased risk of the breast cancer being human epidermal growth factor receptor 2 positive (allele model: OR =1.37, 95% CI =1.03-1.18). Moreover, haplotype analysis showed that Ars1800682Trs763110 was associated to a statistically significant degree with lower risk of breast cancer (OR =0.70, 95% CI =0.53-0.91). These data suggest that the presence of Fas rs1800683 is an important risk factor for breast

Magnetic resonance imaging (MRI) findings among children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) and alcohol related neurodevelopmental disorders (ARND).

PubMed

Anna Dyląg, Katarzyna; Sikora-Sporek, Aleksanda; Bańdo, Bożena; Boroń-Zyss, Joanna; Drożdż, Dorota; Dumnicka, Paulina; Przybyszewska, Katarzyna; Sporek, Mateusz; Walocha, Jerzy W; Wojciechowski, Wadim; Urbanik, Andrzej

The aim of the study was to analyze the findings in MRI (magnetic resonance imaging) of the brain amongst children diagnosed with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) or alcohol related neurodevelopmental disorders (ARND). The issue has been studied in several researches previously but the experts agree that there is still few data on the MRI results in the group of younger children. MRI results of 121 patients with either FAS or pFAS or ARND diagnosed with Canadian criteria were analyzed regarding the presence of abnormalities. The group consisted of 71 patients diagnosed with FAS, 33 diagnosed with pFAS and 17 diagnosed with ARND. The mean age of the patients was 8.03 years (standard deviation 4.07). In the total group of FASD patients 61.98% of the patients’ MRI results were abnormal. The most common abnormality in MRI of the patients were demyelination plaques (incidence 23.1%) and corpus callosum narrowing (20.7%) as well as ventricular asymmetry (18.8%).The demyelination plaques and corpus callosum narrowing were more frequent among children ≤4 years old (41.7% vs 18.6%; p=0.016 and 50.0% vs.13.4%; p<0.001, respectively). Age ≤4 years predicted the presence of demyelination plaques and corpus callosum narrowing independently of FAS diagnosis. Among younger children, multiple central nervous system abnormalities were observed more often than in the older age group (54.2% vs. 14.4%; p<0.001). Odds ratio for multiple changes was 0.84 per one-year increase in age (95% CI 0.73-0.97), p=0.016. Furthermore, in the analysis according to the specific diagnosis, among the patients diagnosed with FAS, multiple anomalies were more common than in pFAS and ARND. Both age ≤4 years and FAS diagnosis were independent predictors for multiple anomalies in multiple logistic regression. In structural brain MRI of younger children, multiple anomalies were found more frequently than among older children. Demyelination plaques and corpus

Clinical utility of urinary soluble Fas in screening for bladder cancer.

PubMed

Srivastava, Anupam Kumar; Singh, Pankaj Kumar; Singh, Dhramveer; Dalela, Divakar; Rath, Srikanta Kumar; Bhatt, Madan Lal Brahma

2016-06-01

Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease. © 2014 Wiley Publishing Asia Pty Ltd.

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

PubMed Central

Volpe, Elisabetta; Sambucci, Manolo; Battistini, Luca; Borsellino, Giovanna

2016-01-01

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas–FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas–FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas–FasL in regulating Th17 and Treg cells’ functions, in the context of MS. PMID:27729910

Oxidative Processing of Latent Fas in the Endoplasmic Reticulum Controls the Strength of Apoptosis

PubMed Central

Anathy, Vikas; Roberson, Elle; Cunniff, Brian; Nolin, James D.; Hoffman, Sidra; Spiess, Page; Guala, Amy S.; Lahue, Karolyn G.; Goldman, Dylan; Flemer, Stevenson; van der Vliet, Albert; Heintz, Nicholas H.; Budd, Ralph C.; Tew, Kenneth D.

2012-01-01

We recently demonstrated that S-glutathionylation of the death receptor Fas (Fas-SSG) amplifies apoptosis (V. Anathy et al., J. Cell Biol. 184:241–252, 2009). In the present study, we demonstrate that distinct pools of Fas exist in cells. Upon ligation of surface Fas, a separate pool of latent Fas in the endoplasmic reticulum (ER) underwent rapid oxidative processing characterized by the loss of free sulfhydryl content (Fas-SH) and resultant increases in S-glutathionylation of Cys294, leading to increases of surface Fas. Stimulation with FasL rapidly induced associations of Fas with ERp57 and glutathione S-transferase π (GSTP), a protein disulfide isomerase and catalyst of S-glutathionylation, respectively, in the ER. Knockdown or inhibition of ERp57 and GSTP1 substantially decreased FasL-induced oxidative processing and S-glutathionylation of Fas, resulting in decreased death-inducing signaling complex formation and caspase activity and enhanced survival. Bleomycin-induced pulmonary fibrosis was accompanied by increased interactions between Fas-ERp57-GSTP1 and S-glutathionylation of Fas. Importantly, fibrosis was largely prevented following short interfering RNA-mediated ablation of ERp57 and GSTP. Collectively, these findings illuminate a regulatory switch, a ligand-initiated oxidative processing of latent Fas, that controls the strength of apoptosis. PMID:22751926

Evaluating the Predictability of South-East Asian Floods Using ECMWF and GloFAS Forecasts

NASA Astrophysics Data System (ADS)

Pillosu, F. M.

2017-12-01

Between July and September 2017, the monsoon season caused widespread heavy rainfall and severe floods across countries in South-East Asia, notably in India, Nepal and Bangladesh, with deadly consequences. According to the U.N., in Bangladesh 140 people lost their lives and 700,000 homes were destroyed; in Nepal at least 143 people died, and more than 460,000 people were forced to leave their homes; in India there were 726 victims of flooding and landslides, 3 million people were affected by the monsoon floods and 2000 relief camps were established. Monsoon season happens regularly every year in South Asia, but local authorities reported the last monsoon season as the worst in several years. What made the last monsoon season particularly severe in certain regions? Are these causes clear from the forecasts? Regarding the meteorological characterization of the event, an analysis of forecasts from the European Centre for Medium-Range Weather Forecast (ECMWF) for different lead times (from seasonal to short range) will be shown to evaluate how far in advance this event was predicted and start discussion on what were the factors that led to such a severe event. To illustrate hydrological aspects, forecasts from the Global Flood Awareness System (GloFAS) will be shown. GloFAS is developed at ECMWF in co-operation with the European Commission's Joint Research Centre (JRC) and with the support of national authorities and research institutions such as the University of Reading. It will become operational at the end of 2017 as part of the Copernicus Emergency Management Service. GloFAS couples state-of-the-art weather forecasts with a hydrological model to provide a cross-border system with early flood guidance information to help humanitarian agencies and national hydro-meteorological services to strengthen and improve forecasting capacity, preparedness and mitigation of natural hazards. In this case GloFAS has shown good potential to become a useful tool for better and

75 FR 23226 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Trade Adjustment Assistance for Farmers AGENCY: Foreign Agricultural Service, USDA. ACTION: Notice. The Administrator, Foreign Agricultural Service (FAS), today accepted a petition, and began a review of a petition, for trade adjustment assistance by the National Asparagus Council on behalf...

Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A)-Mediated changes in Fas Expression and Fas-Dependent Apoptosis: Role of Lyn/Syk activation

PubMed Central

Incrocci, Ryan; Hussain, Samira; Stone, Amanda; Bieging, Kathryn; Alt, Lauren A.C.; Fay, Michael J.; Swanson-Mungerson, Michelle

2015-01-01

Epstein-Barr virus Latent Membrane Protein 2A (LMP2A) is expressed in EBV-infected B cells in the germinal center, a site of significant apoptosis induced by engagement of Fas on activated B cells. Signals from the B cell receptor (BCR) protect germinal center B cells from Fas-mediated apoptosis, and since LMP2A is a BCR mimic, we hypothesized that LMP2A would also protect B cells from Fas-mediated apoptosis. Surprisingly, latently-infected human and murine B cell lines expressing LMP2A were more sensitive to Fas-mediated apoptosis, as determined by increases in Annexin-V staining, and cleavage of caspase-8, −3 and PARP. Additional studies show that LMP2A-expressing B cell lines demonstrate a Lyn- and Syk-dependent increase in sensitivity to Fas-mediated apoptosis, due to an LMP2A-dependent enhancement in Fas expression. These findings demonstrate the ability for LMP2A to directly increase a pro-apoptotic molecule and have implications for EBV latency as well as the treatment of EBV-associated malignancies. PMID:26255694

Expression of miR-625 and Fas in cervical vertebral cartilage endplate.

PubMed

Zhan, Beilei; Zhan, Yan; Wang, Wei; Zhan, Yunzhong; Liu, Bingsheng

2018-01-01

The aim of the present study was to assess miR-625 and Fas expression in normal and degenerative cervical cartilage endplate (CEP) tissues. Following biof-informatics analysis, the Fas gene was predicted to be one of the targets of miR-625. Quantitative PCR (qPCR) and western blotting were used to detect miR-625 and Fas expression in normal and degenerative CEP. A luciferase reporter assay was used to identify whether miR-625 could directly target the 3' untranslated region (3'-UTR) of Fas. Lentiviral overexpression and/or inhibition vectors of miR-625 (pre-miR-625)/antigomiR-625 were constructed to determine whether overexpression or inhibition of miR-625 could affect Fas and B-cell lymphoma 2 (Bcl-2) expression in cartilaginous endplate cells (CECs) and tissues. qPCR analysis demonstrated that miR-625 expression in degenerative CEP was significantly lower than in normal CEP tissue, while the production of Fas in degenerated CEP was significantly higher. Results from western blotting also showed a significant increase in Fas expression in degenerative CEP. miR-625 can bind directly to the 3'-UTR of the Fas gene. However, this inhibition was attenuated by a target mutation in the miR-625-binding site of the 3'-UTR of Fas mRNA. In addition, following transfection of CECs with pre-miR-625 and antigomiR-625, expression of Fas significantly decreased and increased, respectively, and Bcl-2 expression was upregulated and downregulated, respectively. Upregulation of miR-625 can inhibit Fas expression and further affect Bcl-2 expression in CEP degeneration, suggesting that miR-625-mediated inhibition of the Fas gene is important in cervical degeneration.

CD3+ CD8+ NKG2D+ T Lymphocytes Induce Apoptosis and Necroptosis in HLA-Negative Cells via FasL-Fas Interaction.

PubMed

Ivanova, Olga K; Sharapova, Tatiana N; Romanova, Elena A; Soshnikova, Natalia V; Sashchenko, Lidia P; Yashin, Denis V

2017-10-01

An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4 + CD25 + lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8 + lymphocytes. We show that after a tumor antigen contact the IL-2 activated CD8 + lymphocytes acquire ability to lyse tumor cells bearing this antigen. However, activation of the CD8 + lymphocytes in the absence of antigen causes appearance of a cytotoxic population of CD8 + NKG2D + lymphocytes, which are able to lyse HLA-negative cancer cells that have lost the classic mechanism of antigen presentation. These cells recognize the noncanonical MicA antigen on the surface of HLA-negative K562 cells but kill them via the FasL-Fas interaction, as do cytotoxic T lymphocytes. FasL presented on the lymphocyte surface can trigger both apoptosis and necroptosis. Unlike in the case of TNFR1, another cell death receptor, no switching to alternative processes has been observed upon induction of Fas-dependent cell death. It may well be that the apoptotic and necroptotic signals are transduced separately in the latter case, with the ability of FasL + lymphocytes to induce necroptosis allowing them to kill tumor cells that escape apoptosis. J. Cell. Biochem. 118: 3359-3366, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Fas activity mediates airway inflammation during mouse adenovirus type 1 respiratory infection.

PubMed

Adkins, Laura J; Molloy, Caitlyn T; Weinberg, Jason B

2018-06-13

CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions. Copyright © 2018 Elsevier Inc. All rights reserved.

An ontology-based collaborative service framework for agricultural information

USDA-ARS?s Scientific Manuscript database

In recent years, China has developed modern agriculture energetically. An effective information framework is an important way to provide farms with agricultural information services and improve farmer's production technology and their income. The mountain areas in central China are dominated by agri...

Fas-L promotes the stem cell potency of adipose-derived mesenchymal cells.

PubMed

Solodeev, Inna; Meilik, Benjamin; Volovitz, Ilan; Sela, Meirav; Manheim, Sharon; Yarkoni, Shai; Zipori, Dov; Gur, Eyal; Shani, Nir

2018-06-11

Fas-L is a TNF family member known to trigger cell death. It has recently become evident that Fas-L can transduce also non-apoptotic signals. Mesenchymal stem cells (MSCs) are multipotent cells that are derived from various adult tissues. Although MSCs from different tissues display common properties they also display tissue-specific characteristics. Previous works have demonstrated massive apoptosis following Fas-L treatment of bone marrow-derived MSCs both in vitro and following their administration in vivo. We therefore set to examine Fas-L-induced responses in adipose-derived stem cells (ASCs). Human ASCs were isolated from lipoaspirates and their reactivity to Fas-L treatment was examined. ASCs responded to Fas-L by simultaneous apoptosis and proliferation, which yielded a net doubling of cell quantities and a phenotypic shift, including reduced expression of CD105 and increased expression of CD73, in association with increased bone differentiation potential. Treatment of freshly isolated ASCs led to an increase in large colony forming unit fibroblasts, likely produced by early stem cell progenitor cells. Fas-L-induced apoptosis and proliferation signaling were found to be independent as caspase inhibition attenuated Fas-L-induced apoptosis without impacting proliferation, whereas inhibition of PI3K and MEK, but not of JNK, attenuated Fas-L-dependent proliferation, but not apoptosis. Thus, Fas-L signaling in ASCs leads to their expansion and phenotypic shift toward a more potent stem cell state. We speculate that these reactions ensure the survival of ASC progenitor cells encountering Fas-L-enriched environments during tissue damage and inflammation and may also enhance ASC survival following their administration in vivo.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

PubMed Central

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention

HYDRAULIC POWER TRANSFER SYSTEMS. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 9.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

ONE OF A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY-LEVEL STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT COMPETENCY IN UNDERSTANDING BASIC HYDRAULICS AND ITS APPLICATION TO AGRICULTURAL MACHINERY. IT WAS DEVELOPED BY A…

Fas-Antisense Long Noncoding RNA and Acute Myeloid Leukemia: Is There any Relation?

PubMed

Sayad, Arezou; Hajifathali, Abbas; Hamidieh, Amir Ali; Esfandi, Farbod; Taheri, Mohammad

2018-01-27

In recent years, lncRNAs have been considered as potential predictive biomarkers for prognosis of different human cancers. One example is the FAS antisense RNA 1 (FAS-AS1) located in the 10q23.31 region which is transcribed from the opposite strand of the FAS gene. FAS has an important role in regulation of apoptotic pathways and there is an inverse correlation between FAS-AS1 expression level and production of the soluble form of Fas, so that it might have potential as a therapeutic target to improve chemotherapy effectiveness. In the present study we therefore evaluated FAS-AS1 expression in blood samples of de novo AML patients and healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results indicated that the expression level of FAS-AS1 lncRNA demonstrated no significant difference between AML patients and healthy individuals. We conclude from the obtained data that FAS-AS1 is not an informative and reliable biomarker for AML diagnosis, although our results need to be confirmed in further studies. Creative Commons Attribution License

Expression of Fas ligand by microglia: possible role in glioma immune evasion.

PubMed

Badie, B; Schartner, J; Prabakaran, S; Paul, J; Vorpahl, J

2001-11-01

The immune-privileged status of the central nervous system is thought to limit the application of immunotherapy for treatment of malignant brain tumors. Because the Fas pathway has been proposed to play a role in immune evasion, we examined the effect of tumor environment on the expression of Fas ligand (FasL) in a mouse glioma model. Immunoblotting revealed the expression of membrane-bound FasL to nearly double when murine G26 gliomas were propagated intracranially (IC) as compared to subcutaneously (SC). Further analysis by flow cytometry revealed microglia, which were absent in the SC tumors, to account for half of the FasL expression in the IC tumors. Interestingly, when FasL activity was inhibited in IC tumors, the proportion of tumor-infiltrating leukocytes increased three-fold, reaching the same frequency as the SC tumors. These observations suggest that microglia are a major source of FasL expression in brain tumors and possibly contribute to the local immunosuppressive milieu of malignant gliomas.

A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.

PubMed

Menezes, Soraya Maria; Leal, Fabio E; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

2017-01-01

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas hi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fas hi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fas hi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis

Regional services in a research context: USDA climate hubs in the agricultural research service

USDA-ARS?s Scientific Manuscript database

Ten USDA Climate Hubs were created in 2014 to develop and deliver science-based, region-specific information and technologies to better enable agricultural decision-making and management. Of these ten Hubs, half are administered by USDA’s Agricultural Research Service (ARS), an agency with historica...

Fas signaling induces stemness properties in colorectal cancer by regulation of Bmi1.

PubMed

Chen, Jiaxuan; Wang, Yadong; Zhuo, Linghao; Liu, Zhizhong; Liu, Tao; Li, Wenjing; Cai, Yidong; Zheng, Haoxuan

2017-10-01

Fas signaling promotes colorectal cancer (CRC) metastasis by inducing epithelial-mesenchymal transition (EMT). The acquisition of EMT properties in turn induces stemness but the mechanism by which Fas signaling contributes to it still remains unclear. Hence, the aim of this study was to investigate how Fas signaling regulates CRC stemness. For this purpose, soft agar assay, sphere formation assay, cell survival analysis, immunoblot, qRT-PCR, chromatin immunoprecipitation, and luciferase reporter assay were performed. Expression of FasL, Bmi1, and the miR-200c in CRC specimens was examined through immunohistochemistry, qRT-PCR, and immunoblot. In our study, Fas signaling induced stem cell properties in CRC specimens, relying on ERK1/2 MAPK pathway, with Bmi1 being mainly responsible for FasL-induced stemness. FasL treatment promoted Bmi1 expression by inhibiting miR-200c, which targets Bmi1 3'UTR region. Furthermore, FasL-induced Zeb1 binded with miR-200c promoter and inhibited its expression. Moreover, FasL-induced β-catenin nuclear expression promoted Zeb1 expression by binding with Zeb1 promoter. GSK-3β, which regulates β-catenin, was inhibited by FasL-induced ERK1/2 MAPK signaling. Finally, FasL and Bmi1 expression in clinical samples increased during CRC progression, and a positive correlation between them was observed. Patients with high FasL and Bmi1 expression had a worse prognosis than patients with low expression. In conclusion, our results showed that Fas signaling can promote stemness in CRC through the modulation of Bmi1 expression via the ERK1/2 MAPK/GSK-3β/β-catenin/Zeb1/miR-200c axis, suggesting that Fas signaling-based cancer therapies should be administered cautiously, as the activation of this pathway not only leads to apoptosis but also induces stemness in CRC. © 2017 Wiley Periodicals, Inc.

7 CFR 20.2 - Administration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... regulations of this part will be administered by the Foreign Agricultural Service (FAS) under the general supervision of the Administrator, FAS. Information pertaining to these regulations may be obtained from the...

7 CFR 20.2 - Administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... regulations of this part will be administered by the Foreign Agricultural Service (FAS) under the general supervision of the Administrator, FAS. Information pertaining to these regulations may be obtained from the...

7 CFR 20.2 - Administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regulations of this part will be administered by the Foreign Agricultural Service (FAS) under the general supervision of the Administrator, FAS. Information pertaining to these regulations may be obtained from the...

7 CFR 20.2 - Administration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... regulations of this part will be administered by the Foreign Agricultural Service (FAS) under the general supervision of the Administrator, FAS. Information pertaining to these regulations may be obtained from the...

HAT1 induces lung cancer cell apoptosis via up regulating Fas.

PubMed

Han, Na; Shi, Lei; Guo, Qiuyun; Sun, Wei; Yu, Yang; Yang, Li; Zhang, Xiaoxi; Zhang, Mengxian

2017-10-27

The dysfunction of apoptosis is one of the factors contributing to lung cancer (LC) growth. Histone acetyltransferase HAT1 can up regulate cell apoptosis. This study aims to investigate the mechanism by which HAT1 induces LC cell (LCC) apoptosis via up regulating the expression of Fas. In this study, the surgically removed human LC tissues were collected. LCCs were isolated from the LC tissues and analyzed for the expression of HAT1 and Fas by RT-qPCR and Western blotting. We observed that the expression of Fas was negatively correlated with PAR2 in LCCs. Activation of PAR2 suppressed the expression of Fas in normal lung epithelial cells. The expression of HAT1 was lower and positively correlated with Fas expression and negatively correlated with PAR2 expression in LCCs. Activation of PAR2 suppressed Fas expression in lung epithelial cells via inhibiting HAT1. Restoration of HAT1 expression restored Fas expression in LCCs and induced LCC apoptosis. In conclusion, less expression of HAT1 in LCCs was associated with the pathogenesis of LC. Up regulation of HAT1 expression in LCCs can induce LCCs apoptosis, which may be a potential novel therapy for the treatment of LC.

Arthropod genomics research in the United States Department of Agriculture-Agricultural Research Service: Current impacts and future prospects

USDA-ARS?s Scientific Manuscript database

The Agricultural Research Service (ARS) is the intramural research agency of the United States Department of Agriculture (USDA) which employs scientists to conduct basic and applied research aimed to develop and transfer solutions to agricultural problems of high national priority and to ensure food...

Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy.

PubMed

Sejima, Takehiro; Morizane, Shuichi; Hinata, Nobuyuki; Yao, Akihisa; Isoyama, Tadahiro; Saito, Motoaki; Takenaka, Atsushi

2012-01-01

To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis. Copyright © 2012 S. Karger AG, Basel.

[Effects of Naomaitong combined with mobilization of bone marrow mesenchymal stem cells on neuron apoptosis and expressions of Fas, FasL and caspase-3 proteins in rats with cerebral ischemia].

PubMed

Li, Jian-sheng; Liu, Jing-xia; Tian, Yu-shou; Ren, Wei-hong; Zhang, Xin-feng; Wang, Ding-chao

2009-09-01

To observe the effects of Naomaitong, a compound traditional Chinese herbal medicine, combined with mobilization of bone marrow mesenchymal stem cells (BMSCs) on neuron apoptosis in rats with cerebral ischemia, and to explore the possible mechanism by detecting the expressions of Fas, FasL and caspase-3 proteins. Two hundred and two SD rats were divided into sham-operated group, untreated group, recombinant granulocyte colony-stimulating factor (rG-CSF) group, Naomaitong group and Naomaitong plus rG-CSF group (combination group). Focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion using a nylon thread with some modification. Rats in the rG-CSF group and the untreated group were administered with rG-CSF 10 microg/(kg x d) by subcutaneous injection 3 d before and 2 d after the operation respectively, once a day, and rats in the Naomaitong group and the combination group were intragastrically administered Naomaitong before and after the operation until sacrificed. Two, three, seven and fourteen days after operation, count of CD34-positive cells in peripheral blood and CD34 expression in brain tissue were determined. General neural function score (GNFS) was evaluated. Neuron apoptosis, expressions of Fas, FasL and caspase-3 in rat's brain were all measured. Count of CD34-positive cells in peripheral blood and CD34 expression in brain tissue were high in the untreated group, and reached the peak at 3 d and 7 d respectively. CD34 expression in brain tissue was increased in each treated group, especially in the combination group. GNFS was increased at 3 d and 7 d in the untreated group, 7 d and 14 d in the rG-CSF group and the combination group. Expressions of Fas, FasL and caspase-3 were increased 2, 3 and 7 d after operation, while expression of FasL at 2 d in the rG-CSF group, expressions of Fas, FasL and caspase-3 in the combination group were decreased. Expressions of Fas, FasL and caspase-3 at 7 d and 14 d in the combination group

MMP-7, sFas and FasL serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.

PubMed

Szarvas, Tibor; Sevcenco, Sabina; Módos, Orsolya; Keresztes, Dávid; Nyirády, Péter; Csizmarik, Anita; Ristl, Robin; Puhr, Martin; Hoffmann, Michèle J; Niedworok, Christian; Hadaschik, Boris; Maj-Hes, Agnieszka; Shariat, Shahrokh F; Kramer, Gero

2018-05-26

To assess the predictive value of pre-chemotherapy MMP-7, sFas, FasL serum levels as well as their changes during therapy. Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 CRPC patients; 21 docetaxel-resistant who received one single series and 75 docetaxel-sensitive who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Higher pretreatment serum MMP-7, sFas and PSA levels were significantly associated with both docetaxel-resistance (p=0.007, p=0.001, p<0.001, respectively) and shorter cancer-specific survival (p<0.001, p=0.041, p<0.001, respectively). High MMP-7 remained an independent predictor of both docetaxel resistance (HR: 2.298, 95% CI: 1.354-3.899, p=0.002) and poor cancer-specific survival (HR=2.11, 95%Cl 1.36-3.30, p=0.001) in multivariable analyses. Higher increase of MMP-7 levels in the 2 nd treatment holiday and higher increase of PSA levels in the 1 st and 2 nd holidays were predictive of survival. Pretreatment serum MMP-7 levels may help to select CRPC patients who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 alone or in combination with PSA could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

7 CFR 1499.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... processed product for use under the agreement. FAS means the Foreign Agricultural Service acting on behalf... foreign or international organizations (such as agencies of the United Nations) at the discretion of FAS...

7 CFR 1499.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... processed product for use under the agreement. FAS means the Foreign Agricultural Service acting on behalf... foreign or international organizations (such as agencies of the United Nations) at the discretion of FAS...

7 CFR 1499.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... processed product for use under the agreement. FAS means the Foreign Agricultural Service acting on behalf... foreign or international organizations (such as agencies of the United Nations) at the discretion of FAS...

7 CFR 1570.10 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Foreign Agricultural Service (FAS). These criteria are interrelated and will be considered together in... are made available by FAS to enable exporters to meet prevailing world prices for sunflowerseed oil and cottonseed oil in targeted destinations. In the operation of the SOAP and the COAP, FAS will make...

7 CFR 1570.10 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Foreign Agricultural Service (FAS). These criteria are interrelated and will be considered together in... are made available by FAS to enable exporters to meet prevailing world prices for sunflowerseed oil and cottonseed oil in targeted destinations. In the operation of the SOAP and the COAP, FAS will make...

7 CFR 1570.10 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Foreign Agricultural Service (FAS). These criteria are interrelated and will be considered together in... are made available by FAS to enable exporters to meet prevailing world prices for sunflowerseed oil and cottonseed oil in targeted destinations. In the operation of the SOAP and the COAP, FAS will make...

7 CFR 1570.10 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Foreign Agricultural Service (FAS). These criteria are interrelated and will be considered together in... are made available by FAS to enable exporters to meet prevailing world prices for sunflowerseed oil and cottonseed oil in targeted destinations. In the operation of the SOAP and the COAP, FAS will make...

7 CFR 1570.10 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Foreign Agricultural Service (FAS). These criteria are interrelated and will be considered together in... are made available by FAS to enable exporters to meet prevailing world prices for sunflowerseed oil and cottonseed oil in targeted destinations. In the operation of the SOAP and the COAP, FAS will make...

Lack of FasL-mediated killing leads to in vivo tumor promotion in mouse Lewis lung cancer.

PubMed

Lee, J-K; Sayers, T J; Back, T C; Wigginton, J M; Wiltrout, R H

2003-03-01

Lewis lung carcinoma (3LL) cells were constitutively resistant to Fas-mediated apoptosis, but overexpression of Fas on 3LL cells allowed Fas-mediated apoptosis after crosslinking with agonist anti-Fas antibody (Jo2) in vitro. Surprisingly, Fas-overexpressing 3LL cells showed enhanced in vivo tumor progression, whereas no promotion of in vivo tumor growth was observed for dominant negative (DN) Fas-overexpressing 3LL transfectants in which the cytoplasmic death domain was deleted. In addition, the promotion of in vivo tumor growth by Fas-overexpression was reduced in gld (FasL-mutation) mice compared to normal mice. These data indicate that intact Fas/FasL cell signaling is required for the promotion of in vivo tumor growth by Fas overexpression in 3LL cells. In contrast to the efficient Fas-mediated killing induced in vitro by crosslinking with anti-Fas antibody, Fas-overexpressing 3LL cells were resistant in vitro to Fas-mediated apoptosis by activated T cells or transient FasL transfection. These data suggest that agonist anti-Fas antibody and natural FasL can transmit qualitatively different signals, and crosslinking of Fas with natural FasL on 3LL cells does not deliver the expected death signal. Thus, our results demonstrate that in some cases overexpression of Fas can result in a survival advantage for tumor cells in vivo.

48 CFR 470.201 - Acquisition of commodities and freight shipment for Foreign Agricultural Service programs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and freight shipment for Foreign Agricultural Service programs. 470.201 Section 470.201 Federal....201 Acquisition of commodities and freight shipment for Foreign Agricultural Service programs. (a... this section, in contracts for the Foreign Agricultural Service for commodities and related freight...

48 CFR 470.201 - Acquisition of commodities and freight shipment for Foreign Agricultural Service programs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... and freight shipment for Foreign Agricultural Service programs. 470.201 Section 470.201 Federal....201 Acquisition of commodities and freight shipment for Foreign Agricultural Service programs. (a... this section, in contracts for the Foreign Agricultural Service for commodities and related freight...

48 CFR 470.201 - Acquisition of commodities and freight shipment for Foreign Agricultural Service programs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and freight shipment for Foreign Agricultural Service programs. 470.201 Section 470.201 Federal....201 Acquisition of commodities and freight shipment for Foreign Agricultural Service programs. (a... this section, in contracts for the Foreign Agricultural Service for commodities and related freight...

48 CFR 470.201 - Acquisition of commodities and freight shipment for Foreign Agricultural Service programs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... and freight shipment for Foreign Agricultural Service programs. 470.201 Section 470.201 Federal....201 Acquisition of commodities and freight shipment for Foreign Agricultural Service programs. (a... this section, in contracts for the Foreign Agricultural Service for commodities and related freight...

48 CFR 470.201 - Acquisition of commodities and freight shipment for Foreign Agricultural Service programs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... and freight shipment for Foreign Agricultural Service programs. 470.201 Section 470.201 Federal....201 Acquisition of commodities and freight shipment for Foreign Agricultural Service programs. (a... this section, in contracts for the Foreign Agricultural Service for commodities and related freight...

Molecular cloning, functional identification and expressional analyses of FasL in Tilapia, Oreochromis niloticus.

PubMed

Ma, Tai-yang; Wu, Jin-ying; Gao, Xiao-ke; Wang, Jing-yuan; Zhan, Xu-liang; Li, Wen-sheng

2014-10-01

FasL is the most extensively studied apoptosis ligand. In 2000, tilapia FasL was identified using anti-human FasL monoclonal antibody by Evans's research group. Recently, a tilapia FasL-like protein of smaller molecule weight was predicted in Genbank (XM_003445156.2). Based on several clues drawn from previous studies, we cast doubt on the authenticity of the formerly identified tilapia FasL. Conversely, using reverse transcription polymerase chain reaction (RT-PCR), the existence of the predicted FasL-like was verified at the mRNA level (The Genbank accession number of the FasL mRNA sequence we cloned is KM008610). Through multiple alignments, this FasL-like protein was found to be highly similar to the FasL of the Japanese flounder. Moreover, we artificially expressed the functional region of the predicted protein and later confirmed its apoptosis-inducing activity using a methyl thiazolyl tetrazolium (MTT) assay, Annexin-V/Propidium iodide (PI) double staining, and DNA fragment detection. Supported by these evidences, we suggest that the predicted protein is the authentic tilapia FasL. To advance this research further, tilapia FasL mRNA and its protein across different tissues were quantified. High expression levels were identified in the tilapia immune system and sites where active cell turnover conservatively occurs. In this regard, FasL may assume an active role in the immune system and cell homeostasis maintenance in tilapia, similar to that shown in other species. In addition, because the distribution pattern of FasL mRNA did not synchronize with that of the protein, post-transcriptional expression regulation is suggested. Such regulation may be dominated by potential adenylate- and uridylate-rich elements (AREs) featuring AUUUA repeats found in the 3' untranslated region (UTR) of tilapia FasL mRNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

PubMed

Lai, J H; Ho, L J; Lu, K C; Chang, D M; Shaio, M F; Han, S H

2001-06-01

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Cytokine-mediated FOXO3a phosphorylation suppresses FasL expression in hemopoietic cell lines: investigations of the role of Fas in apoptosis due to cytokine starvation.

PubMed

Behzad, Hayedeh; Jamil, Sarwat; Denny, Trisha A; Duronio, Vincent

2007-05-01

We have investigated phosphatidylinositol 3-kinase (PI3K)-dependent survival signalling pathways using several cytokines in three different hemopoietic cell lines, MC/9, FDC-P1, and TF-1. Cytokines caused PI3K- and PKB-dependent phosphorylation of FOXO3a (previously known as FKHRL1) at three distinct sites. Following cytokine withdrawal or PI3K inhibition, both of which are known to lead to apoptosis, there was a loss of FOXO3a phosphorylation, and a resulting increase in forkhead transcriptional activity, along with increased expression of Fas Ligand (FasL), which could be detected at the cell surface. Concurrently, an increase in cell surface expression of Fas was also detected. Despite the presence of both FasL and Fas, there was no detectable evidence that activation of Fas-mediated apoptotic events was contributing to apoptosis resulting from cytokine starvation or inhibition of PI3K activity. Thus, inhibition of FOXO3a activity is mediated by the PI3K-PKB pathway, but regulation of FasL is not the primary means by which cell survival is regulated in cytokine-dependent hemopoietic cells. We were also able to confirm increased expression of known FOXO3a targets, Bim and p27kip1. Together, these results support the conclusion that mitochondrial-mediated signals play the major role in apoptosis of hemopoietic cells due to loss of cytokine signalling.

CRHR2/Ucn2 signaling is a novel regulator of miR-7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas-mediated apoptosis.

PubMed

Pothoulakis, Charalabos; Torre-Rojas, Monica; Duran-Padilla, Marco A; Gevorkian, Jonathan; Zoras, Odysseas; Chrysos, Emmanuel; Chalkiadakis, George; Baritaki, Stavroula

2018-01-15

Colorectal cancer (CRC) responds poorly to immuno-mediated cytotoxicity. Underexpression of corticotropin-releasing-hormone-receptor-2 (CRHR2) in CRC, promotes tumor survival, growth and Epithelial to Mesenchymal Transition (EMT), in vitro and in vivo. We explored the role of CRHR2 downregulation in CRC cell resistance to Fas/FasL-mediated apoptosis and the underlying molecular mechanism. CRC cell sensitivity to CH11-induced apoptosis was compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing CRC cell lines and targets of CRHR2/Ucn2 signaling were identified through in vitro and ex vivo analyses. Induced CRHR2/Ucn2 signaling in SW620 and DLD1 cells increased specifically their sensitivity to CH11-mediated apoptosis, via Fas mRNA and protein upregulation. CRC compared to control tissues had reduced Fas expression that was associated with lost CRHR2 mRNA, poor tumor differentiation and high risk for distant metastasis. YY1 silencing increased Fas promoter activity in SW620 and re-sensitized them to CH11-apoptosis, thus suggesting YY1 as a putative transcriptional repressor of Fas in CRC. An inverse correlation between Fas and YY1 expression was confirmed in CRC tissue arrays, while elevated YY1 mRNA was clinically relevant with advanced CRC grade and higher risk for distant metastasis. CRHR2/Ucn2 signaling downregulated specifically YY1 expression through miR-7 elevation, while miR-7 modulation in miR-7 high SW620-CRHR2+ and miR-7 low HCT116 cells, had opposite effects on YY1 and Fas expressions and cell sensitivity to CH11-killing. CRHR2/Ucn2 signaling is a negative regulator of CRC cell resistance to Fas/FasL-apoptosis via targeting the miR-7/YY1/Fas circuitry. CRHR2 restoration might prove effective in managing CRC response to immune-mediated apoptotic stimuli. © 2017 UICC.

75 FR 43485 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

.... The Administrator of the Foreign Agricultural Service (FAS) today accepted and began a review of a... cash benefits. FOR FURTHER INFORMATION CONTACT: Trade Adjustment Assistance for Farmers Staff, FAS, USDA, by phone: (202) 720-0638, or (202) 690-0633; or by e-mail: [email protected]fas.usda.gov ; or...

75 FR 41432 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... Foreign Agricultural Service (FAS) denied a petition (No. 2010010) for trade adjustment assistance (TAA... INFORMATION CONTACT: Trade Adjustment Assistance for Farmers Staff, FAS, USDA, by phone: (202) 720-0638, or (202) 690-0633; or by e-mail: [email protected]fas.usda.gov ; or visit the TAA for Farmers' Web site...

Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction

PubMed Central

Cruz, Anthony C.; Ramaswamy, Madhu; Ouyang, Claudia; Klebanoff, Christopher A.; Sengupta, Prabuddha; Yamamoto, Tori N.; Meylan, Françoise; Thomas, Stacy K.; Richoz, Nathan; Eil, Robert; Price, Susan; Casellas, Rafael; Rao, V. Koneti; Lippincott-Schwartz, Jennifer; Restifo, Nicholas P.; Siegel, Richard M.

2016-01-01

Mutations affecting the apoptosis-inducing function of the Fas/CD95 TNF-family receptor result in autoimmune and lymphoproliferative disease. However, Fas can also costimulate T-cell activation and promote tumour cell growth and metastasis. Palmitoylation at a membrane proximal cysteine residue enables Fas to localize to lipid raft microdomains and induce apoptosis in cell lines. Here, we show that a palmitoylation-defective Fas C194V mutant is defective in inducing apoptosis in primary mouse T cells, B cells and dendritic cells, while retaining the ability to enhance naive T-cell differentiation. Despite inability to efficiently induce cell death, the Fas C194V receptor prevents the lymphoaccumulation and autoimmunity that develops in Fas-deficient mice. These findings indicate that induction of apoptosis through Fas is dependent on receptor palmitoylation in primary immune cells, and Fas may prevent autoimmunity by mechanisms other than inducing apoptosis. PMID:28008916

15 CFR 2011.206 - Suspension or revocation of individual certificates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... appealed to the Director, Import Policy and Trade Analysis Division, Foreign Agricultural Service (FAS), U... opportunity for an informal hearing on such matter. A further appeal may be made to the Administrator, FAS, U...

15 CFR 2011.206 - Suspension or revocation of individual certificates.

Code of Federal Regulations, 2013 CFR

2013-01-01

... appealed to the Director, Import Policy and Trade Analysis Division, Foreign Agricultural Service (FAS), U... opportunity for an informal hearing on such matter. A further appeal may be made to the Administrator, FAS, U...

Expression of TRAIL and Fas in Primary Hyperparathyroidism.

PubMed

Segiet, Oliwia Anna; Deska, Mariusz; Mielańczyk, Łukasz; Brzozowa-Zasada, Marlena; Buła, Grzegorz; Gawrychowski, Jacek; Wojnicz, Romuald

2017-08-01

Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland. Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity. The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands. In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions.

The expression of Fas Ligand by macrophages and its upregulation by human immunodeficiency virus infection.

PubMed Central

Dockrell, D H; Badley, A D; Villacian, J S; Heppelmann, C J; Algeciras, A; Ziesmer, S; Yagita, H; Lynch, D H; Roche, P C; Leibson, P J; Paya, C V

1998-01-01

Fas/Fas Ligand (FasL) interactions play a significant role in peripheral T lymphocyte homeostasis and in certain pathological states characterized by T cell depletion. In this study, we demonstrate that antigen-presenting cells such as monocyte-derived human macrophages (MDM) but not monocyte-derived dendritic cells express basal levels of FasL. HIV infection of MDM increases FasL protein expression independent of posttranslational mechanisms, thus highlighting the virus-induced transcriptional upregulation of FasL. The in vitro relevance of these observations is confirmed in human lymphoid tissue. FasL protein expression is constitutive and restricted to tissue macrophages and not dendritic cells. Moreover, a significant increase in macrophage-associated FasL is observed in lymphoid tissue from HIV (+) individuals (P < 0.001), which is further supported by increased levels of FasL mRNA using in situ hybridization. The degree of FasL protein expression in vivo correlates with the degree of tissue apoptosis (r = 0.761, P < 0. 001), which is significantly increased in tissue from HIV-infected patients (P < 0.001). These results identify human tissue macrophages as a relevant source for FasL expression in vitro and in vivo and highlight the potential role of FasL expression in the immunopathogenesis of HIV infection. PMID:9616211

Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function.

PubMed

Item, Flurin; Wueest, Stephan; Lemos, Vera; Stein, Sokrates; Lucchini, Fabrizio C; Denzler, Rémy; Fisser, Muriel C; Challa, Tenagne D; Pirinen, Eija; Kim, Youngsoo; Hemmi, Silvio; Gulbins, Erich; Gross, Atan; O'Reilly, Lorraine A; Stoffel, Markus; Auwerx, Johan; Konrad, Daniel

2017-09-07

Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.

METAL FUSION AND FABRICATION WELDING. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE, NUMBER 6.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

ONE IN A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, OR SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT UNDERSTANDING OF WELDING EQUIPMENT AND SUPPLIES, AND ABILITY TO PERFORM SKILLS REQUIRED OF AGRICULTURAL MECHANICS. IT WAS…

Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions

PubMed Central

Ashton, Sandra V.; Whitley, Guy St. J.; Dash, Philip R.; Wareing, Mark; Crocker, Ian P.; Baker, Philip N.; Cartwright, Judith E.

2014-01-01

Objective Invasion of uterine spiral arteries by extravillous trophoblasts in the first trimester of pregnancy results in loss of endothelial and musculoelastic layers. This remodeling is crucial for an adequate blood supply to the fetus with a failure to remodel implicated in the etiology of the hypertensive disorder preeclampsia. The mechanism by which trophoblasts induce this key process is unknown. This study gives the first insights into the potential mechanisms involved. Methods and Results Spiral arteries were dissected from nonplacental bed biopsies obtained at Caesarean section, and a novel model was used to mimic in vivo events. Arteries were cultured with trophoblasts in the lumen, and apoptotic changes in the endothelial layer were detected after 20 hours, leading to loss of endothelium by 96 hours. In vitro, coculture experiments showed that trophoblasts stimulated apoptosis of primary decidual endothelial cells and an endothelial cell line. This was blocked by caspase inhibition and NOK2, a FasL blocking antibody. NOK2 also abrogated trophoblast-induced endothelial apoptosis in the vessel model. Conclusions Extravillous trophoblast induction of endothelial apoptosis is a possible mechanism by which the endothelium is removed, and vascular remodeling may occur in uterine spiral arteries. Fas/FasL interactions have an important role in trophoblast-induced endothelial apoptosis. PMID:15499040

Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-Induced Apoptosis and Lung Injury in Mice.

PubMed

Nagamine, Yusuke; Tojo, Kentaro; Yazawa, Takuya; Takaki, Shunsuke; Baba, Yasuko; Goto, Takahisa; Kurahashi, Kiyoyasu

2016-12-01

Alveolar epithelial injury and increased alveolar permeability are hallmarks of acute respiratory distress syndrome. Apoptosis of lung epithelial cells via the Fas/Fas ligand (FasL) pathway plays a critical role in alveolar epithelial injury. Activation of hypoxia-inducible factor (HIF)-1 by inhibition of prolyl hydroxylase domain proteins (PHDs) is a possible therapeutic approach to attenuate apoptosis and organ injury. Here, we investigated whether treatment with dimethyloxalylglycine (DMOG), an inhibitor of PHDs, could attenuate Fas/FasL-dependent apoptosis in lung epithelial cells and lung injury. DMOG increased HIF-1α protein expression in vitro in MLE-12 cells, a murine alveolar epithelial cell line. Treatment of MLE-12 cells with DMOG significantly suppressed cell surface expression of Fas and attenuated FasL-induced caspase-3 activation and apoptotic cell death. Inhibition of the HIF-1 pathway by echinomycin or small interfering RNA transfection abolished these antiapoptotic effects of DMOG. Moreover, intraperitoneal injection of DMOG in mice increased HIF-1α expression and decreased Fas expression in lung tissues. DMOG treatment significantly attenuated caspase-3 activation, apoptotic cell death in lung tissue, and the increase in alveolar permeability in mice instilled intratracheally with FasL. In addition, inflammatory responses and histopathological changes were also significantly attenuated by DMOG treatment. In conclusion, inhibition of PHDs protects lung epithelial cells from Fas/FasL-dependent apoptosis through HIF-1 activation and attenuates lung injury in mice.

Regional services in a research context: USDA Climate Hubs in the USDA Agricultural Research Service

USDA-ARS?s Scientific Manuscript database

Ten USDA Climate Hubs were created in 2014 to develop and deliver science-based, region-specific information and technologies to better enable agricultural decision-making and management. Of these ten Hubs, half are administered by USDA’s Agricultural Research Service (ARS), an agency with historica...

76 FR 55868 - Notice of Funding Availability: Inviting Applications for the Food for Progress Program; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... Agricultural Service (FAS) published a notice in the Federal Register on July 28, 2011, inviting proposals for... proposals through October 26, 2011. This date was incorrect and, by this notice, FAS is correcting the due... by e-mail at: [email protected]fas.usda.gov . SUPPLEMENTARY INFORMATION: Correction In the Federal Register of...

75 FR 41430 - Trade Adjustment Assistance for Farmers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

.... The Administrator of the Foreign Agricultural Service (FAS) has denied a petition (No. 2010014) for... FURTHER INFORMATION CONTACT: Trade Adjustment Assistance for Farmers Staff, FAS, USDA, by phone: (202) 720-0638, or (202) 690-0633; or by e-mail: [email protected]fas.usda.gov ; or visit the TAA for Farmers' Web...

Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

PubMed

Agrebi, N; Ben-Mustapha, I; Matoussi, N; Dhouib, N; Ben-Ali, M; Mekki, N; Ben-Ahmed, M; Larguèche, B; Ben Becher, S; Béjaoui, M; Barbouche, M R

2017-10-01

Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations. Copyright © 2017 Elsevier Inc. All rights reserved.

A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

PubMed Central

Menezes, Soraya Maria; Leal, Fabio E.; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V.; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F.; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

2017-01-01

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fashi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating

Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain?

PubMed Central

Saas, P; Walker, P R; Hahne, M; Quiquerez, A L; Schnuriger, V; Perrin, G; French, L; Van Meir, E G; de Tribolet, N; Tschopp, J; Dietrich, P Y

1997-01-01

Astrocytomas are among the most common brain tumors that are usually fatal in their malignant form. They appear to progress without significant impedance from the immune system, despite the presence of intratumoral T cell infiltration. To date, this has been thought to be the result of T cell immunosuppression induced by astrocytoma-derived cytokines. Here, we propose that cell contact-mediated events also play a role, since we demonstrate the in vivo expression of Fas ligand (FasL/CD95L) by human astrocytoma and the efficient killing of Fas-bearing cells by astrocytoma lines in vitro and by tumor cells ex vivo. Functional FasL is expressed by human, mouse, and rat astrocytoma and hence may be a general feature of this nonlymphoid tumor. In the brain, astrocytoma cells can potentially deliver a death signal to Fas+ cells which include infiltrating leukocytes and, paradoxically, astrocytoma cells themselves. The expression of FasL by astrocytoma cells may extend the processes that are postulated to occur in normal brain to maintain immune privilege, since we also show FasL expression by neurons. Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system. PMID:9077524

Structural and Biophysical Characterization of the Interactions between the Death Domain of Fas Receptor and Calmodulin*

PubMed Central

Fernandez, Timothy F.; Samal, Alexandra B.; Bedwell, Gregory J.; Chen, Yabing; Saad, Jamil S.

2013-01-01

The extrinsic apoptotic pathway is initiated by cell surface death receptors such as Fas. Engagement of Fas by Fas ligand triggers a conformational change that allows Fas to interact with adaptor protein Fas-associated death domain (FADD) via the death domain, which recruits downstream signaling proteins to form the death-inducing signaling complex (DISC). Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells, suggesting a novel role of CaM in Fas-mediated signaling. CaM antagonists induce apoptosis through a Fas-related mechanism in cholangiocarcinoma and other cancer cell lines possibly by inhibiting Fas-CaM interactions. The structural determinants of Fas-CaM interaction and the underlying molecular mechanisms of inhibition, however, are unknown. Here we employed NMR and biophysical techniques to elucidate these mechanisms. Our data show that CaM binds to the death domain of Fas (FasDD) with an apparent dissociation constant (Kd) of ∼2 μm and 2:1 CaM:FasDD stoichiometry. The interactions between FasDD and CaM are endothermic and entropically driven, suggesting that hydrophobic contacts are critical for binding. We also show that both the N- and C-terminal lobes of CaM are important for binding. NMR and surface plasmon resonance data show that three CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide, tamoxifen, and trifluoperazine) greatly inhibit Fas-CaM interactions by blocking the Fas-binding site on CaM. Our findings provide the first structural evidence for Fas-CaM interactions and mechanism of inhibition and provide new insight into the molecular basis for a novel role of CaM in regulating Fas-mediated apoptosis. PMID:23760276

Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations

PubMed Central

Price, Susan; Shaw, Pamela A.; Seitz, Amy; Joshi, Gyan; Davis, Joie; Niemela, Julie E.; Perkins, Katie; Hornung, Ronald L.; Folio, Les; Rosenberg, Philip S.; Puck, Jennifer M.; Hsu, Amy P.; Lo, Bernice; Pittaluga, Stefania; Jaffe, Elaine S.; Fleisher, Thomas A.; Lenardo, Michael J.

2014-01-01

Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αβ+ T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients. This trial was registered at www.clinicaltrials.gov as #NCT00001350. PMID:24398331

Induction of apoptosis in breast cancer cells in vitro by Fas ligand reverse signaling.

PubMed

Kolben, Thomas; Jeschke, Udo; Reimer, Toralf; Karsten, Nora; Schmoeckel, Elisa; Semmlinger, Anna; Mahner, Sven; Harbeck, Nadia; Kolben, Theresa M

2018-02-01

The Fas-antigen is a cell surface receptor that transduces apoptotic signals into cells. The purpose of this study was to evaluate FasL expression in breast cancer and to elucidate the role of its signaling in different breast cancer cell lines. T47D and MCF7 cells were used and cultured in Dulbecco's modified Eagle's medium. FasL translocation to the membrane was achieved by culturing the cells in the presence of human interferon-γ (IFNγ). Translocation was detected by immunofluorescence. The ability of a Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by cell death detection ELISA. After incubation with IFNγ for 4 h and 18 h, apoptosis was assessed in response to treatment with Fas:Fc. Immunofluorescence revealed that the used cell lines were positive for FasL which was increased and changed to more membrane-bound FasL expression after IFNγ stimulation. After stimulation with 50 IU/ml IFNγ, Fas:Fc significantly increased MCF7 apoptosis (1.39 ± 0.06-fold, p = 0.0004) after 18 h. After stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4 h (1.49 ± 0.15-fold, p = 0.018) and 18 h (1.30 ± 0.06-fold, p = 0.013). In T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and addition of Fas:Fc (1.6 ± 0.08-fold, p = 0.03). Membrane-bound FasL expression could be induced by IFNγ in a breast cancer cell model. More importantly, in the presence of IFNγ the Fas:Fc fusion protein was able to transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing apoptosis. The current findings support further in vivo studies regarding FasL activation as a potential target for therapeutic intervention in breast cancer.

75 FR 68000 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Hiawatha National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... of Agriculture, Forest Service, Hiawatha National Forest, Escanaba, MI and University of Michigan... of Agriculture, Forest Service, Hiawatha National Forest, Escanaba, MI, and in the physical custody... Agriculture, Forest Service, professional staff in consultation with representatives of the Bay Mills Indian...

An integrated approach to monitoring ecosystem services and agriculture: implications for sustainable agricultural intensification in Rwanda.

PubMed

Rosa, Melissa F; Bonham, Curan A; Dempewolf, Jan; Arakwiye, Bernadette

2017-01-01

Maintaining the long-term sustainability of human and natural systems across agricultural landscapes requires an integrated, systematic monitoring system that can track crop productivity and the impacts of agricultural intensification on natural resources. This study presents the design and practical implementation of a monitoring framework that combines satellite observations with ground-based biophysical measurements and household surveys to provide metrics on ecosystem services and agricultural production at multiple spatial scales, reaching from individual households and plots owned by smallholder farmers to 100-km 2 landscapes. We developed a set of protocols for monitoring and analyzing ecological and agricultural household parameters within two 10 × 10-km landscapes in Rwanda, including soil fertility, crop yield, water availability, and fuelwood sustainability. Initial results suggest providing households that rely on rainfall for crop irrigation with timely climate information and improved technical inputs pre-harvest could help increase crop productivity in the short term. The value of the monitoring system is discussed as an effective tool for establishing a baseline of ecosystem services and agriculture before further change in land use and climate, identifying limitations in crop production and soil fertility, and evaluating food security, economic development, and environmental sustainability goals set forth by the Rwandan government.

Invasive species research in the United States Department of Agriculture-Agricultural Research Service.

PubMed

Carruthers, Raymond I

2003-01-01

Invasive pests cause huge losses both to agricultural production systems and to the natural environment through displacing native species and decreasing biodiversity. It is now estimated that many thousand exotic insect, weed and pathogen species have been established in the USA and that these invasive species are responsible for a large portion of the $130 billion losses estimated to be caused by pests each year. The Agricultural Research Service (ARS) has responded with extensive research and action programs aimed at understanding these problems and developing new management approaches for their control. This paper provides an overview of some of the ARS research that has been conducted on invasive species over the past few years and addresses both different categories of research and some specific pest systems of high interest to the US Department of Agriculture.

Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.

PubMed

Goel, N; Ulrich, D T; St Clair, E W; Fleming, J A; Lynch, D H; Seldin, M F

1995-12-01

To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.

Agriculture Supplies & Services. Volume 2 of 3.

ERIC Educational Resources Information Center

Kansas State Univ., Manhattan.

The second of three volumes included in a secondary agricultural supplies and services curriculum guide, this volume contains units of instruction in three major areas: (1) Animal Science, (2) Supervised Training Programs--Farm Business Management, and (3) Career Selection/Public Relations. Typical of the sixteen units included in the first…

Low concentrations of doxycycline attenuates FasL-induced apoptosis in HeLa cells.

PubMed

Yoon, Jung Mi; Koppula, Sushruta; Huh, Se Jong; Hur, Sun Jin; Kim, Chan Gil

2015-07-24

Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in the concentration range of 10-40 µg/mL. However, the effect of DC in apoptotic signaling at much low concentrations was not studied. The present study investigated the attenuation effect of low dose of DC on FasL-induced apoptosis in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA fragmentation, flow cytometry analysis, and western blotting. In the present findings we showed that low concentration of DC (<2.0 µg/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells. FasL treatment to HeLa cells resulted in a concentration-dependent induction of cell death, and treatment with low concentrations of DC (0.1-2 µg/mL) significantly (p < 0.001) attenuated the FasL-induced cell death as measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Further, the FasL-induced apoptotic features in HeLa cells, such as morphological changes, DNA fragmentation and cell cycle arrest was also inhibited by DC (0.5 µg/mL). Tetracycline and minocycline also showed similar anti-apoptotic effects but were not significant when compared to DC, tested at same concentrations. Further, DC (0.01-16 µg/mL) did not influence the hydrogen peroxide- or cisplatin-induced intrinsic apoptotic pathway in HeLa cells. Protein analysis using Western blotting confirmed that FasL-induced cleavage/activation of caspase-8 and caspase-3, were inhibited by DC treatment at low concentration (0.5 µg/mL). Considering the overall data, we report for the first time that DC exhibited anti-apoptotic effects at low concentrations in HeLa cells by inhibition of caspase activation via FasL-induced extrinsic pathway.

77 FR 32993 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Rio Grande...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

... Inventory Completion: U.S. Department of Agriculture, Forest Service, Rio Grande National Forest, CO AGENCY: National Park Service, Interior. ACTION: Notice. SUMMARY: The U.S. Department of Agriculture, Forest.... Department of Agriculture, Forest Service, Rio Grande National Forest, 1803 W. Highway 160, Monte Vista, CO...

MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer.

PubMed

Yan, Chunxiao; Yang, Fan; Zhou, Chunxia; Chen, Xuejun; Han, Xuechuan; Liu, Xueqin; Ma, Hongyun; Zheng, Wei

2015-01-01

This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas.

Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

PubMed

Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

2014-06-01

Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

COURSE OUTLINE FOR AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

THE OBJECTIVE OF THE 16-MODULE COURSE OUTLINED IN THIS GUIDE IS TO HELP TEACHERS PREPARE FORMER FARMERS, HIGH SCHOOL DROPOUTS AND GRADUATES, AND UNEMPLOYED, AND EMPLOYED PERSONS FOR OCCUPATIONAL ENTRY AS AGRICULTURAL MACHINERY SETUP MEN, MECHANIC'S HELPERS, MECHANICS, PARTS MEN, AND SERVICE SUPERVISORS. IT WAS DEVELOPED BY A NATIONAL TASK FORCE ON…

77 FR 11584 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Gila National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

.... Department of Agriculture, Forest Service, Gila National Forest, Silver City, NM, and Field Museum of Natural... of Agriculture, Forest Service, Gila National Forest and the Field Museum of Natural History have... contact the U.S. Department of Agriculture, Forest Service, Gila National Forest. Repatriation of the...

76 FR 43718 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Gila National...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

.... Department of Agriculture, Forest Service, Gila National Forest, Silver City, NM and Field Museum of Natural... of Agriculture, Forest Service, Gila National Forest and the Field Museum of Natural History have... may contact the U.S. Department of Agriculture, Forest Service, Gila National Forest. Repatriation of...

Expression of FAS-L Differs from Primary to Relapsed Low-grade Gliomas and Predicts Progression-free Survival.

PubMed

Werner, Jan-Michael; Kuhl, Saskia; Stavrinou, Pantelis; Röhn, Gabriele; Krischek, Boris; Blau, Tobias; Goldbrunner, Roland; Timmer, Marco

2017-12-01

The tumor necrosis factor FAS is overexpressed in high-grade gliomas (HGG). Only little is known about FAS or FAS ligand (FAS-L) in low-grade gliomas (LGG). We explored FAS/FAS-L expression in LGG, focusing on differences in primary and relapsed LGG and on its prognostic value. A total of 133 glioma samples (73 LGG, 60 HGG) were collected. The LGG samples included 15 matched pairs of primary and relapsed tumors. RT-PCR was performed to measure FAS/FAS-L expression, using subunit A, flavoprotein variant (SDHA) as housekeeper. Clinical data included progression free- (PFS) and overall survival (OS). LGG showed significantly lower FAS but higher FAS-L expression than HGG. The FAS-L expression was higher in primary compared to relapsed LGG and had a positive prognostic value concerning PFS (median 45.20 vs. 31.37 months). FAS-L could act as a prognostic marker and potential target in primary LGG. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

FAS/FASL gene polymorphisms in Turkish patients with chronic myeloproliferative disorders.

PubMed

Ozdemirkiran, Fusun Gediz; Nalbantoglu, Sinem; Gokgoz, Zafer; Payzin, Bahriye Kadriye; Vural, Filiz; Cagirgan, Seckin; Berdeli, Afig

2017-03-01

Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group ( p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis ( p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups ( p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations ( p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

TRACTOR REPAIR. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 16.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

THE PURPOSE OF THIS GUIDE IS TO HELP TEACHERS PREPARE POSTSECONDARY STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS. IT WAS DESIGNED BY A NATIONAL TASK FORCE ON THE BASIS OF RESEARCH FROM STATE STUDIES. THE MAJOR OBJECTIVE IS TO DEVELOP (1) AN UNDERSTANDING OF THE…

Mutation in Fas Ligand Impairs Maturation of Thymocytes Bearing Moderate Affinity T Cell Receptors

PubMed Central

Boursalian, Tamar E.; Fink, Pamela J.

2003-01-01

Fas ligand, best known as a death-inducer, is also a costimulatory molecule required for maximal proliferation of mature antigen-specific CD4+ and CD8+ T cells. We now extend the role of Fas ligand by showing that it can also influence thymocyte development. T cell maturation in some, but not all, strains of TCR transgenic mice is severely impaired in thymocytes expressing mutant Fas ligand incapable of interacting with Fas. Mutant Fas ligand inhibits neither negative selection nor death by neglect. Instead, it appears to modulate positive selection of thymocytes expressing both class I– and class II–restricted T cell receptors of moderate affinity for their positively selecting ligands. Fas ligand is therefore an inducer of death, a costimulator of peripheral T cell activation, and an accessory molecule in positive selection. PMID:12860933

Multipath for Agricultural and Rural Information Services in China

NASA Astrophysics Data System (ADS)

Ge, Ningning; Zang, Zhiyuan; Gao, Lingwang; Shi, Qiang; Li, Jie; Xing, Chunlin; Shen, Zuorui

Internet cannot provide perfect information services for farmers in rural regions in China, because farmers in rural regions can hardly access the internet by now. But the wide coverage of mobile signal, telephone line, and television network, etc. gave us a chance to solve the problem. The integrated pest management platform of Northern fruit trees were developed based on the integrated technology, which can integrate the internet, mobile and fixed-line telephone network, and television network, to provide integrated pest management(IPM) information services for farmers in rural regions in E-mail, telephone-voice, short message, voice mail, videoconference or other format, to users' telephone, cell phone, personal computer, personal digital assistant(PDA), television, etc. alternatively. The architecture and the functions of the system were introduced in the paper. The system can manage the field monitoring data of agricultural pests, deal with enquiries to provide the necessary information to farmers accessing the interactive voice response(IVR) in the system with the experts on-line or off-line, and issue the early warnings about the fruit tree pests when it is necessary according to analysis on the monitoring data about the pests of fruit trees in variety of ways including SMS, fax, voice and intersystem e-mail.The system provides a platform and a new pattern for agricultural technology extension with a high coverage rate of agricultural technology in rural regions, and it can solve the problem of agriculture information service 'last kilometer' in China. The effectiveness of the system was certified.

Service Oriented Architecture for Wireless Sensor Networks in Agriculture

NASA Astrophysics Data System (ADS)

Sawant, S. A.; Adinarayana, J.; Durbha, S. S.; Tripathy, A. K.; Sudharsan, D.

2012-08-01

Rapid advances in Wireless Sensor Network (WSN) for agricultural applications has provided a platform for better decision making for crop planning and management, particularly in precision agriculture aspects. Due to the ever-increasing spread of WSNs there is a need for standards, i.e. a set of specifications and encodings to bring multiple sensor networks on common platform. Distributed sensor systems when brought together can facilitate better decision making in agricultural domain. The Open Geospatial Consortium (OGC) through Sensor Web Enablement (SWE) provides guidelines for semantic and syntactic standardization of sensor networks. In this work two distributed sensing systems (Agrisens and FieldServer) were selected to implement OGC SWE standards through a Service Oriented Architecture (SOA) approach. Online interoperable data processing was developed through SWE components such as Sensor Model Language (SensorML) and Sensor Observation Service (SOS). An integrated web client was developed to visualize the sensor observations and measurements that enables the retrieval of crop water resources availability and requirements in a systematic manner for both the sensing devices. Further, the client has also the ability to operate in an interoperable manner with any other OGC standardized WSN systems. The study of WSN systems has shown that there is need to augment the operations / processing capabilities of SOS in order to understand about collected sensor data and implement the modelling services. Also, the very low cost availability of WSN systems in future, it is possible to implement the OGC standardized SWE framework for agricultural applications with open source software tools.

Agriculture Supplies & Services. Volume 1 of 3.

ERIC Educational Resources Information Center

Kansas State Univ., Manhattan.

The first of three volumes included in a secondary agricultural supplies and services curriculum guide, this volume contains units of instruction in two major areas: (1) plant and soil science and (2) leadership (Future Farmers of America). Typical of the nineteen units included in the first section are the following: Plant Insect Control, Plant…

75 FR 67998 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Chattahoochee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... DEPARTMENT OF THE INTERIOR National Park Service Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Chattahoochee-Oconee National Forests, Gainesville, GA AGENCY... Agriculture, Forest Service, Chattahoochee-Oconee National Forests, Gainesville, GA. The human remains and...

Mapping environmental land use conflict potentials and ecosystem services in agricultural watersheds.

PubMed

Kim, Ilkwon; Arnhold, Sebastian

2018-07-15

In mountainous watersheds, agricultural land use cause changes in ecosystem services, with trade-offs between crop production and erosion regulation. Management of these watersheds can generate environmental land use conflicts among regional stakeholders with different interests. Although several researches have made a start in mapping land use conflicts between human activities and conservation, spatial assessment of land use conflicts on environmental issues and ecosystem service trade-offs within agricultural areas has not been fully considered. In this study, we went further to map land use conflicts between agricultural preferences for crop production and environmental emphasis on erosion regulation. We applied an agricultural land suitability index, based on multi-criteria analysis, to estimate the spatial preference of agricultural activities, while applying the Revised Universal Soil Loss Equation (RUSLE) to reflect the environmental importance of soil erosion. Then, we classified the agricultural catchment into four levels of land use conflicts (lowest, low, high and highest) according to preference and importance of farmland areas, and we compared the classes by crop type. Soil loss in agricultural areas was estimated as 45.1thayr, and agricultural suitability as 0.873; this indicated that land use conflicts in the catchment could arise between severe soil erosion (environmental importance) and agricultural suitability (land preferences). Dry-field farms are mainly located in areas of low land use conflict level, where land preference outweighs environmental importance. When we applied farmland management scenarios with consideration of services, conversion to highest-conflict areas (Scenario 1) as 7.5% of the total area could reduce soil loss by 24.6%, while fallow land management (Scenario 2) could decrease soil loss 19.4% more than the current scenario (Business as usual). The result could maximize land management plans by extracting issues of spatial

Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

PubMed

Bennett, M W; O'connell, J; O'sullivan, G C; Roche, D; Brady, C; Kelly, J; Collins, J K; Shanahan, F

1999-02-01

Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. Thirty paraffin wax embedded human gastric adenocarcinomas. FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer

PubMed Central

Yan, Chunxiao; Yang, Fan; Zhou, Chunxia; Chen, Xuejun; Han, Xuechuan; Liu, Xueqin; Ma, Hongyun; Zheng, Wei

2015-01-01

This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas. PMID:26045776

Promoter hypermethylation and downregulation of the FAS gene may be involved in colorectal carcinogenesis.

PubMed

Manoochehri, Mehdi; Borhani, Nasim; Karbasi, Ashraf; Koochaki, Ameneh; Kazemi, Bahram

2016-07-01

Aberrant DNA methylation has been investigated in carcinogenesis and as biomarker for the early detection of colorectal cancer (CRC). The present study aimed to define the methylation status in the regulatory elements of two proapoptotic genes, Fas cell surface death receptor (FAS) and BCL2-associated X protein (BAX). DNA methylation analysis was performed in tumor and adjacent normal tissue using Hpa II/ Msp I restriction digestion and methylation-specific polymerase chain reaction (PCR). The results observed downregulation of the FAS and BAX genes in the CRC tissues compared with the adjacent normal samples. Furthermore, demethylation using 5-aza-2'-deoxycytidine treatment followed by reverse-transcription quantitative PCR were performed on the HT-29 cell line to measure BAX and FAS mRNA expression following demethylation. The 5-aza-2'-deoxycytidine treatment resulted in significant FAS gene upregulation in the HT-29 cell line, but no significant difference in BAX expression. Furthermore, analysis of CpG islands in the FAS gene promoter revealed that the FAS promoter was significantly hypermethylated in 53.3% of tumor tissues compared with adjacent normal samples. Taken together, the results indicate that decreased expression of the FAS gene due to hypermethylation of its promoter may lead to apoptotic resistance, and acts as an important step during colorectal carcinogenesis.

Novel insights into FAS defects underlying autoimmune lymphoproliferative syndrome revealed by studies in consanguineous patients.

PubMed

Ben-Mustapha, Imen; Agrebi, Nourhen; Barbouche, Mohamed-Ridha

2018-03-01

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly associated with autoimmune manifestations primarily directed against blood cells. Herein, we review the heterogeneous ALPS molecular bases and discuss recent findings revealed by the study of consanguineous patients. Indeed, this peculiar genetic background favored the identification of a novel form of AR ALPS-FAS associated with normal or residual protein expression, expanding the spectrum of ALPS types. In addition, rare mutational mechanisms underlying the splicing defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein expression. These findings will help decipher critical regions required for the tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS molecular bases in endogamous populations helps to better classify the disease subgroups and to unravel the Fas pathway functioning. ©2017 Society for Leukocyte Biology.

Partial tolerance of subcutaneously transplanted xenogeneic tumour cell graft by Fas-mediated immunosuppression

PubMed Central

SAWADA, TAKAHIRO; KOJI, TAKEHIKO; HISHIKAWA, YOSHITAKA; KISHIMOTO, KOJI; NAGAYASU, TAKESHI; TAKAHASHI, TAKAO; OKA, TADAYUKI; AYABE, HIROYOSHI

2001-01-01

Certain anti-Fas antibodies, such as RMF2, induce apoptosis of Fas-expressing cells. We applied the Fas/anti-Fas system to induce killing of Fas-expressing immunocytes with resultant immunosuppression. W7TM-1 tumour cells, a rat T-cell line, were inoculated subcutaneously in BALB/c mice and tumour growth was monitored in untreated mice and in mice treated with RMF2. Prior to treatment with RMF2, we examined the expression of Fas in isolated splenocytes and in tumour-infiltrating lymphocytes by flow cytometry and immunohistochemistry, respectively. There was a remarkable increase in Fas-positive lymphocytes, including natural killer (NK) cells, among splenocytes at day 5 after tumour cell inoculation. The number of Fas-positive infiltrating lymphocytes also increased markedly, from day 5 to day 10. We then examined whether RMF2 could induce apoptosis of Fas-positive activated lymphocytes isolated from the spleen at day 5 in vitro. Terminal deoxy (d) -UTP nick end labelling (TUNEL) and Annexin V staining methods showed apoptosis of isolated cells when incubated with RMF2, and typical apoptotic features were confirmed by 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. Furthermore, suppression of cellular and humoral immunity was noted in RMF2-treated mice by mixed lymphocyte reaction and assay of serum levels of immunoglobulin G, respectively. Finally, treatment of animals with RMF2 daily from day 5 to day 9 could maintain the tumour size, while the tumour mass began to diminish in untreated mice immediately after reaching a maximum size. We confirmed the enhancing effects of long-term treatment with RMF2, through the induction of immunosuppression, on the growth of unvascularized xenogeneic tumour cell grafts. PMID:11380695

Small Interfering RNA-Mediated Suppression of Fas Modulate Apoptosis and Proliferation in Rat Intervertebral Disc Cells.

PubMed

Park, Jong-Beom; Park, Chanjoo

2017-10-01

In vitro cell culture model. To investigate the effect of small interfering RNA (siRNA) on Fas expression, apoptosis, and proliferation in serum-deprived rat disc cells. Synthetic siRNA can trigger an RNA interference (RNAi) response in mammalian cells and precipitate the inhibition of specific gene expression. However, the potential utility of siRNA technology in downregulation of specific genes associated with disc cell apoptosis remains unclear. Rat disc cells were isolated and cultured in the presence of either 10% fetal bovine serum (FBS) (normal control) or 0% FBS (serum deprivation to induce apoptosis) for 48 hours. Fas expression, apoptosis, and proliferation were determined. Additionally, siRNA oligonucleotides against Fas (Fas siRNA) were transfected into rat disc cells to suppress Fas expression. Changes in Fas expression were assessed by reverse transcription-polymerase chain reaction and semiquantitatively analyzed using densitometry. The effect of Fas siRNA on apoptosis and proliferation of rat disc cells were also determined. Negative siRNA and transfection agent alone (Mock) were used as controls. Serum deprivation increased apoptosis by 40.3% ( p <0.001), decreased proliferation by 45.3% ( p <0.001), and upregulated Fas expression. Additionally, Fas siRNA suppressed Fas expression in serum-deprived cultures, with 68.5% reduction at the mRNA level compared to the control cultures ( p <0.001). Finally, Fas siRNA-mediated suppression of Fas expression significantly inhibited apoptosis by 9.3% and increased proliferation by 21% in serum-deprived cultures ( p <0.05 for both). The observed dual positive effect of Fas siRNA might be a powerful therapeutic approach for disc degeneration by suppression of harmful gene expression.

Agricultural Industries Transportation Services (AITS) statewide needs assessment study.

DOT National Transportation Integrated Search

2003-05-01

The California Department of Transportation (Caltrans) funded the Agricultural Industries Transportation Services Statewide Needs Assessment Study to determine the existence and extent of the unmet transportation needs among the states agricultura...

Career opportunities for college graduates with the Agricultural Research Service Agency of the U.S. Department of Agriculture

USDA-ARS?s Scientific Manuscript database

The Agricultural Research Service is the principal scientific research agency of the U.S. Department of Agriculture. This agency employs more than 7,600 people working at various locations in the United States and U.S. territories. Careers for new scientists span a variety of disciplines such as c...

On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice.

PubMed

Balomenos, Dimitrios; Shokri, Rahman; Daszkiewicz, Lidia; Vázquez-Mateo, Cristina; Martínez-A, Carlos

2017-01-01

Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient ( lpr ) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4 + and CD8 + T cells, and more so of the double-negative TCR + CD4 - CD8 - B220 + T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo . We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes.

75 FR 44808 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

....S. Department of Agriculture, Forest Service, Coconino National Forest, Flagstaff, AZ, and Arizona... of Agriculture, Forest Service, Coconino National Forest, Flagstaff, AZ, and in the possession of the.... Department of Agriculture, Forest Service, Coconino National Forest, have determined that, pursuant to 25 U.S...

75 FR 45656 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Siuslaw National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... DEPARTMENT OF THE INTERIOR National Park Service Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Siuslaw National Forest, Waldport, OR AGENCY: National Park Service... of the U.S. Department of Agriculture, Forest Service, Siuslaw National Forest, Waldport, OR. The...

75 FR 52014 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Cherokee National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

... DEPARTMENT OF THE INTERIOR National Park Service Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Cherokee National Forest, Cleveland, TN AGENCY: National Park Service... funerary objects in the control of the U.S. Department of Agriculture, Forest Service, Cherokee National...

The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats.

PubMed

Milanovic, Desanka; Pesic, Vesna; Loncarevic-Vasiljkovic, Natasa; Pavkovic, Zeljko; Popic, Jelena; Kanazir, Selma; Jevtovic-Todorovic, Vesna; Ruzdijic, Sabera

2016-10-01

A number of experimental studies have reported that exposure to common, clinically used anesthetics induce extensive neuroapoptosis and cognitive impairment when applied to young rodents, up to 2 weeks old, in phase of rapid synaptogenesis. Propofol is the most used general anesthetic in clinical practice whose mechanisms of neurotoxicity on the developing brain remains to be examined in depth. This study investigated effects of different exposures to propofol anesthesia on Fas receptor and Fas ligand expressions, which mediate proapoptotic and proinflammation signaling in the brain. Propofol (20 mg/kg) was administered to 7-day-old rats in multiple doses sufficient to maintain 2-, 4- and 6-h duration of anesthesia. Animals were sacrificed at 0, 4, 16 and 24 h after termination of anesthesia. It was found that propofol anesthesia induced Fas/FasL and downstream caspase-8 expression more prominently in the thalamus than in the cortex. Opposite, Bcl-2 and caspase-9, markers of intrinsic pathway activation, were shown to be more influenced by propofol treatment in the cortex. Further, we have established upregulation of caspase-1 and IL-1β cytokine transcription as well as subsequent activation of microglia that is potentially associated with brain inflammation. Behavioral analyses revealed that P35 and P60 animals, neonatally exposed to propofol, had significantly higher motor activity during three consecutive days of testing in the open field, though formation of the intersession habituation was not prevented. This data, together with our previous results, contributes to elucidation of complex mechanisms of propofol toxicity in developing brain.

Promoter hypermethylation and downregulation of the FAS gene may be involved in colorectal carcinogenesis

PubMed Central

MANOOCHEHRI, MEHDI; BORHANI, NASIM; KARBASI, ASHRAF; KOOCHAKI, AMENEH; KAZEMI, BAHRAM

2016-01-01

Aberrant DNA methylation has been investigated in carcinogenesis and as biomarker for the early detection of colorectal cancer (CRC). The present study aimed to define the methylation status in the regulatory elements of two proapoptotic genes, Fas cell surface death receptor (FAS) and BCL2-associated X protein (BAX). DNA methylation analysis was performed in tumor and adjacent normal tissue using HpaII/MspI restriction digestion and methylation-specific polymerase chain reaction (PCR). The results observed downregulation of the FAS and BAX genes in the CRC tissues compared with the adjacent normal samples. Furthermore, demethylation using 5-aza-2′-deoxycytidine treatment followed by reverse-transcription quantitative PCR were performed on the HT-29 cell line to measure BAX and FAS mRNA expression following demethylation. The 5-aza-2′-deoxycytidine treatment resulted in significant FAS gene upregulation in the HT-29 cell line, but no significant difference in BAX expression. Furthermore, analysis of CpG islands in the FAS gene promoter revealed that the FAS promoter was significantly hypermethylated in 53.3% of tumor tissues compared with adjacent normal samples. Taken together, the results indicate that decreased expression of the FAS gene due to hypermethylation of its promoter may lead to apoptotic resistance, and acts as an important step during colorectal carcinogenesis. PMID:27347139

FAS 33: accurately recording effects of changing prices.

PubMed

Sage, L G

1987-02-01

FAS 33 addresses the problem of distortion in conventional historical cost financial statements because of changing prices. It requires 1300 business enterprises to report selected changing price data on a supplementary basis. It has been demonstrated that it is also feasible and beneficial for hospitals to present price disclosures as supplementary information to their financial statements. The possible application of FAS 33 is supported on the basis that the accounting and reporting methods of healthcare institutions are similar to the accounting and reporting practices of profit-seeking entities.

Possible association of FAS and FASLG polymorphisms with the risk of idiopathic azoospermia in southeast Turkey.

PubMed

Balkan, Mahmut; Atar, Murat; Erdal, Mehmet Emin; Rustemoğlu, Aydin; Yildiz, Ismail; Gunesacar, Ramazan; Hatipoğlu, Namık Kemal; Bodakçi, Mehmet Nuri; Ay, Ozlem Izci; Çevik, Kenan

2014-06-01

To investigate the association of the genetic variants of FAS/FASLG cell death pathway genes in male infertility, we genotyped the FAS -670A/G, -1377G/A, and FASLG -124A/G single-nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction in 108 infertile men with idiopathic azoospermia and in 125 proven fertile controls. The distribution of genotypes and alleles for SNPs at FAS -1377G/A and FASLG -124A/G loci were determined not to be statistically different between the case and control groups. However, the genotype frequencies of SNPs, FAS -670AA and FAS -670AG, were found to be significantly different between the case and control groups. Whereas the FAS -670AA genotype might be regarded as a higher predisposition for idiopathic azoospermia, FAS -670AG could be interpreted to mean that this genotype provides protection against idiopathic azoospermia. The study of combined genotype and haplotype frequencies has found statistically significant differences between case and control subjects for some combinations. The AA-GG binary genotype for the FAS670 and FAS1377 loci couple, in particular, may have a high degree of predisposition to idiopathic azoospermia. Our results suggest that FAS -670A/G SNP may be a genetic predisposing factor of idiopathic azoospermia among southeastern Anatolian men. Larger studies are needed to verify these findings. Furthermore, our data indicated a possible linkage between the FAS and FASLG genes and idiopathic azoospermia.

Fas Versatile Signaling and Beyond: Pivotal Role of Tyrosine Phosphorylation in Context-Dependent Signaling and Diseases

PubMed Central

Chakrabandhu, Krittalak; Hueber, Anne-Odile

2016-01-01

The Fas/FasL system is known, first and foremost, as a potent apoptosis activator. While its proapoptotic features have been studied extensively, evidence that the Fas/FasL system can elicit non-death signals has also accumulated. These non-death signals can promote survival, proliferation, migration, and invasion of cells. The key molecular mechanism that determines the shift from cell death to non-death signals had remained unclear until the recent identification of the tyrosine phosphorylation in the death domain of Fas as the reversible signaling switch. In this review, we present the connection between the recent findings regarding the control of Fas multi-signals and the context-dependent signaling choices. This information can help explain variable roles of Fas signaling pathway in different pathologies. PMID:27799932

Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.

PubMed

Headen, Devon M; Woodward, Kyle B; Coronel, María M; Shrestha, Pradeep; Weaver, Jessica D; Zhao, Hong; Tan, Min; Hunckler, Michael D; Bowen, William S; Johnson, Christopher T; Shea, Lonnie; Yolcu, Esma S; García, Andrés J; Shirwan, Haval

2018-06-04

Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4 + CD25 + FoxP3 + T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

STARD13 promotes hepatocellular carcinoma apoptosis by acting as a ceRNA for Fas.

PubMed

Zhang, Hai; Wang, Fang; Hu, Yahua

2017-02-01

To study the roles of STARD13 in cellular apoptosis of hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry analyses showed that the expression levels of STARD13 and Fas were lower in clinical HCC tissues than in normal tissues and were positively correlated, which is consistent with the results analyzed by The Cancer Genome Atlas (TCGA) data. Patients with higher STARD13 or Fas expression levels had longer overall survival. Additionally, STARD13 3'-UTR enhanced cellular apoptosis and the 3'-UTRs of STARD13 and Fas were predicted to harbor nine similar miRNA binding sites. And STARD13 3'-UTR promoted Fas expression in a 3'-UTR- and miRNA-dependent way and increased the sensitivity of HCC cells to chemotherapy. Importantly, the coding sequence of STARD13 did not increase Fas expression. STARD13 3'-UTR promotes HCC apoptosis through acting as a ceRNA for Fas.

Critical Zone Services as Environmental Assessment Criteria in Intensively Managed Agricultural Landscapes

NASA Astrophysics Data System (ADS)

Richardson, M.; Kumar, P.

2016-12-01

The critical zone (CZ) includes the biophysical processes occurring from the top of the vegetation canopy to the weathering zone below the groundwater table. CZ services provide a measure for the goods and benefits derived from CZ processes. In intensively managed landscapes (IML), the provisioning, supporting, and regulating services are altered through anthropogenic energy inputs to derive more productivity, as agricultural products, from these landscapes than would be possible under natural conditions. However, the energy or cost equivalents of alterations to CZ functions within landscape profiles are unknown. The valuation of CZ services in energy or monetary terms provides a more concrete tool for characterizing seemingly abstract environmental damages from agricultural production systems. A multi-layer canopy-root-soil model is combined with nutrient and water flux models to simulate the movement of nutrients throughout the soil system. This data enables the measurement of agricultural anthropogenic impacts to the CZ's nutrient cycling supporting services and atmospheric stabilizing regulating services defined by the flux of carbon and nutrients. Such measurements include soil carbon storage, soil carbon respiration, nitrate leaching, and nitrous oxide flux into the atmosphere. Additionally, the socioeconomic values of corn feed and ethanol define the primary productivity supporting services of each crop use.In the debate between feed production and corn-based ethanol production, measured nutrient CZ services can cost up to four times more than traditionally estimated CO2 equivalences for the entire bioenergy production system. Energy efficiency in addition to environmental impacts demonstrate how the inclusion of CZ services is necessary in accounting for the entire life cycle of agricultural production systems. These results conclude that feed production systems are more energy efficient and less environmentally costly than corn-based ethanol systems.

Building an Agricultural Extension Services System Supported by ICTs in Tanzania: Progress Made, Challenges Remain

ERIC Educational Resources Information Center

Sanga, C.; Kalungwizi, V. J.; Msuya, C. P.

2013-01-01

The conventional agricultural extension service in Tanzania is mainly provided by extension officers visiting farmers to provide agricultural advisory service. This system of extension service provision faces a number of challenges including the few number of extension officers and limited resources. This article assesses the effectiveness of an…

Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

PubMed

Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

2016-08-01

Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

DIESEL ENGINE SYSTEMS. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 15.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

ONE OF A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY STUDENTS FOR AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT UNDERSTANDING OF THE CONSTRUCTION AND OPERATING PRINCIPLES OF DIESEL ENGINES. IT WAS DEVELOPED BY A NATIONAL TASK FORCE ON…

Women's Access to Agricultural Extension Services in Botswana.

ERIC Educational Resources Information Center

Bettles, F. M.

Extension services to women in rural Botswana, particularly emphasized since the women's extension program began in 1975, must take into account constraints faced by female farmers, as past development processes have concentrated on male perceptions of concern (the beef industry, modernizing the economy). In Botswana, agriculture has traditionally…

Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2.

PubMed

Raqib, Rubhana; Ekberg, Caroline; Sharkar, Protim; Bardhan, Pradip K; Zychlinsky, Arturo; Sansonetti, Philippe J; Andersson, Jan

2002-06-01

Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival.

Improved isolation and purification of functional human Fas receptor extracellular domain using baculovirus-silkworm expression system.

PubMed

Muraki, Michiro; Honda, Shinya

2011-11-01

To achieve an efficient isolation of human Fas receptor extracellular domain (hFasRECD), a fusion protein of hFasRECD with human IgG1 heavy chain Fc domain containing thrombin cleavage sequence at the junction site was overexpressed using baculovirus-silkworm larvae expression system. The hFasRECD part was separated from the fusion protein by the effective cleavage of the recognition site with bovine thrombin. Protein G column treatment of the reaction mixture and the subsequent cation-exchange chromatography provided purified hFasRECD with a final yield of 13.5mg from 25.0 ml silkworm hemolymph. The functional activity of the product was examined by size-exclusion chromatography analysis. The isolated hFasRECD less strongly interacted with human Fas ligand extracellular domain (hFasLECD) than the Fc domain-bridged counterpart, showing the contribution of antibody-like avidity in the latter case. The purified glycosylated hFasRECD presented several discrete bands in the disulphide-bridge non-reducing SDS-PAGE analysis, and virtually all of the components were considered to participate in the binding to hFasLECD. The attached glycans were susceptible to PNGase F digestion, but mostly resistant to Endo Hf digestion under denaturing conditions. One of the components exhibited a higher susceptibility to PNGase F digestion under non-denaturing conditions. Copyright © 2011 Elsevier Inc. All rights reserved.

Examining the psychometric properties of the Hindi version of Family Accommodation Scale-Self-Report (FAS-SR).

PubMed

Mahapatra, Ananya; Gupta, Rishi; Patnaik, Kuppili Pooja; Pattanaik, Raman Deep; Khandelwal, Sudhir Kumar

2017-10-01

Family accommodation (FA) is the phenomenon whereby caregivers assist or facilitate rituals or behaviours related to obsessive compulsive disorder (OCD). There is a need for a self-rated instrument to assess this construct in resource-strained clinical settings of India. To explore the factor structure of Hindi version of Family Accommodation Scale-Self Rated version (FAS-SR) and compare its validity with the gold standard Family Accommodation Scale-Interviewer Rated (FAS-IR) scale. The Hindi version of FAS-SR scale and FAS-IR scale was applied on 105 caregivers of patients with OCD. The initial factor analysis yielded three-factor models with an eigenvalue of >1 and the total variance explained by these factors was 72.017%. The internal consistency of the 19-item scale was 0.93 indicating good inter-item correlation. There was a significant positive correlation between FAS-IR scale total score and all the factors of the FAS-SR Scale. The average measure ICC was 0.889 with a 95% confidence interval from 0.783 to 0.981 (F (62,84)=37.547, p<001) indicating high degree of reliability between the Hindi version of FAS-SR and the FAS-IR scale. FAS-SR is a practical alternative to FAS-IR and has the potential to be used widely in an Indian setting. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing corn for biofuel production reduces biocontrol services in agricultural landscapes

PubMed Central

Landis, Douglas A.; Gardiner, Mary M.; van der Werf, Wopke; Swinton, Scott M.

2008-01-01

Increased demand for corn grain as an ethanol feedstock is altering U.S. agricultural landscapes and the ecosystem services they provide. From 2006 to 2007, corn acreage increased 19% nationally, resulting in reduced crop diversity in many areas. Biological control of insects is an ecosystem service that is strongly influenced by local landscape structure. Here, we estimate the value of natural biological control of the soybean aphid, a major pest in agricultural landscapes, and the economic impacts of reduced biocontrol caused by increased corn production in 4 U.S. states (Iowa, Michigan, Minnesota, and Wisconsin). For producers who use an integrated pest management strategy including insecticides as needed, natural suppression of soybean aphid in soybean is worth an average of $33 ha−1. At 2007–2008 prices these services are worth at least $239 million y−1 in these 4 states. Recent biofuel-driven growth in corn planting results in lower landscape diversity, altering the supply of aphid natural enemies to soybean fields and reducing biocontrol services by 24%. This loss of biocontrol services cost soybean producers in these states an estimated $58 million y−1 in reduced yield and increased pesticide use. For producers who rely solely on biological control, the value of lost services is much greater. These findings from a single pest in 1 crop suggest that the value of biocontrol services to the U.S. economy may be underestimated. Furthermore, we suggest that development of cellulosic ethanol production processes that use a variety of feedstocks could foster increased diversity in agricultural landscapes and enhance arthropod-mediated ecosystem services. PMID:19075234

Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection.

PubMed

Macias, Juan; Japón, Miguel A; Sáez, Carmen; Palacios, Rosa B; Mira, José A; García-García, José A; Merchante, Nicolás; Vergara, Salvador; Lozano, Fernando; Gómez-Mateos, Jesús; Pineda, Juan A

2005-11-01

Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection. Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection. One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes (adjusted odds ratio [AOR], 7.4 [95% confidence interval {CI}, 3.8-14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5-4.5]). In HCV/HIV-coinfected patients, CD4+ cell nadir<200 cells/mL was associated with both Fas expression (AOR, 2.9 [95% CI, 1.3-6.8]) and hepatocyte apoptosis (AOR, 2.3 [95% CI, 1.1-4.9]). HCV/HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4+ cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.

FAS apoptotic inhibitory molecule 2 is a stress-induced intrinsic neuroprotective factor in the retina.

PubMed

Pawar, Mercy; Busov, Boris; Chandrasekhar, Aaruran; Yao, Jingyu; Zacks, David N; Besirli, Cagri G

2017-10-01

We report the neuroprotective role of FAS apoptotic inhibitory molecule 2 (FAIM2), an inhibitor of the FAS signaling pathway, during stress-induced photoreceptor apoptosis. Retinal detachment resulted in increased FAIM2 levels in photoreceptors with higher amounts detected at the tips of outer segments. Activation of FAS death receptor via FAS-ligand led to JNK-mediated FAIM2 phosphorylation, decreased proteasome-mediated degradation and increased association with the FAS receptor. Photoreceptor apoptosis was accelerated in Faim2 knockout mice following experimental retinal detachment. We show that FAIM2 is primarily involved in reducing stress-induced photoreceptor cell death but this effect was transient. FAIM2 was found to interact with both p53 and HSP90 following the activation of the FAS death pathway and FAIM2/HSP90 interaction was dependent on the phosphorylation of FAIM2. Lack of FAIM2 led to increased expression of proadeath genes Fas and Ripk1 in the retina under physiologic conditions. These results demonstrate that FAIM2 is an intrinsic neuroprotective factor activated by stress in photoreceptors and delays FAS-mediated photoreceptor apoptosis. Modulation of this pathway to increase FAIM2 expression may be a potential therapeutic option to prevent photoreceptor death.

H3K9 Trimethylation Silences Fas Expression to Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance

PubMed Central

Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Choi, Jeong-Hyeon; Li, Xia; Liu, Feiyan; Figueroa, Mario; Oberlies, Nicholas H.; Pearce, Cedric; Bollag, Wendy B.; Nayak-Kapoor, Asha; Liu, Kebin

2015-01-01

The Fas-FasL effector mechanism plays a key role in cancer immune surveillance by host T cells, but metastatic human colon carcinoma often uses silencing Fas expression as a mechanism of immune evasion. The molecular mechanism under FAS transcriptional silencing in human colon carcinoma is unknown. We performed genome-wide ChIP-Sequencing analysis and identified that the FAS promoter is enriched with H3K9me3 in metastatic human colon carcinoma cells. H3K9me3 level in the FAS promoter region is significantly higher in metastatic than in primary cancer cells, and is inversely correlated with Fas expression level. We discovered that verticillin A is a selective inhibitor of histone methyltransferases SUV39H1, SUV39H2 and G9a/GLP that exhibit redundant functions in H3K9 trimethylation and FAS transcriptional silencing. Genome-wide gene expression analysis identified FAS as one of the verticillin A target genes. Verticillin A treatment decreased H3K9me3 level in the FAS promoter and restored Fas expression. Furthermore, verticillin A exhibited greater efficacy than Decitabine and Vorinostat in overcoming colon carcinoma resistance to FasL-induced apoptosis. Verticillin A also increased DR5 expression and overcame colon carcinoma resistance to DR5 agonist drozitumab-induced apoptosis. Interestingly, verticillin A overcame metastatic colon carcinoma resistance to 5-Fluouracil in vitro and in vivo. Using an orthotopic colon cancer mouse model, we demonstrated that tumor-infiltrating cytotoxic T lymphocytes are FasL+ and FasL-mediated cancer immune surveillance is essential for colon carcinoma growth control in vivo. Our findings determine that H3K9me3 of the FAS promoter is a dominant mechanism underlying FAS silencing and resultant colon carcinoma immune evasion and progression. PMID:26136424

Ecosystem Services Provided by Agricultural Land as Modeled by Broad Scale Geospatial Analysis

NASA Astrophysics Data System (ADS)

Kokkinidis, Ioannis

Agricultural ecosystems provide multiple services including food and fiber provision, nutrient cycling, soil retention and water regulation. Objectives of the study were to identify and quantify a selection of ecosystem services provided by agricultural land, using existing geospatial tools and preferably free and open source data, such as the Virginia Land Use Evaluation System (VALUES), the North Carolina Realistic Yield Expectations (RYE) database, and the land cover datasets NLCD and CDL. Furthermore I sought to model tradeoffs between provisioning and other services. First I assessed the accuracy of agricultural land in NLCD and CDL over a four county area in eastern Virginia using cadastral parcels. I uncovered issues concerning the definition of agricultural land. The area and location of agriculture saw little change in the 19 years studied. Furthermore all datasets have significant errors of omission (11.3 to 95.1%) and commission (0 to 71.3%). Location of agriculture was used with spatial crop yield databases I created and combined with models I adapted to calculate baseline values for plant biomass, nutrient composition and requirements, land suitability for and potential production of biofuels and the economic impact of agriculture for the four counties. The study area was then broadened to cover 97 counties in eastern Virginia and North Carolina, investigating the potential for increased regional grain production through intensification and extensification of agriculture. Predicted yield from geospatial crop models was compared with produced yield from the NASS Survey of Agriculture. Area of most crops in CDL was similar to that in the Survey of Agriculture, but a yield gap is present for most years, partially due to weather, thus indicating potential for yield increase through intensification. Using simple criteria I quantified the potential to extend agriculture in high yield land in other uses and modeled the changes in erosion and runoff should

75 FR 70026 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Pacific Northwest...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF THE INTERIOR National Park Service [2253-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Pacific Northwest Region, Gifford Pinchot National Forest... the U.S. Department of Agriculture, Forest Service, Pacific Northwest Region, Gifford Pinchot National...

Long-term trends in railroad service and capacity for U.S. agriculture

DOT National Transportation Integrated Search

2000-11-01

In this paper, the long-term trends in railroad services and capacity for U.S. agriculture are identified and described, particularly in terms of what these trends portend for agricultural shippers absent any change in the economically deregulated en...

Chloral Hydrate Treatment Induced Apoptosis of Macrophages via Fas Signaling Pathway.

PubMed

Cai, Jun; Peng, Yanxia; Chen, Ting; Liao, Huanjin; Zhang, Lifang; Chen, Qiuhua; He, Yiming; Wu, Ping; Xie, Tong; Pan, Qingjun

2016-12-10

BACKGROUND There are recent reports on several anesthetics that have anti-inflammatory and anti-infective effects apart from their uses for pain relief and muscle relaxation. Chloral hydrate is a clinical anesthetic drug and sedative that has also been reported to attenuate inflammatory response, but the mechanisms are not clearly understood. MATERIAL AND METHODS This study investigated the effect of chloral hydrate treatment on the apoptosis of macrophages and explored the underlying mechanisms. RAW264.7 macrophages were treated with various concentrations of chloral hydrate for various lengths of time. Morphological changes were observed under a light microscope and apoptosis was detected with annexin-V-FITC/PI double-staining assay, Hochest 33258 and DNA ladder assay, the expression of Fas/FasL was detected with a flow cytometer, and the Fas signaling pathway was assessed by Western blotting. RESULTS The results showed that chloral hydrate treatment induced the morphology of RAW264.7 macrophages to change shape from typical fusiform to round in a concentration- and time-dependent manner, and was finally suspended in the supernatant. For the induction of apoptosis, chloral hydrate treatment induced the apoptosis of RAW264.7 macrophages from early-to-late stage apoptosis in a concentration- and time-dependent manner. For the mechanism, chloral hydrate treatment induced higher expression of Fas on RAW264.7 macrophages, and was also associated with changes in the expression of proteins involved in Fas signaling pathways. CONCLUSIONS Chloral hydrate treatment can induce the apoptosis of RAW264.7 macrophages through the Fas signaling pathway, which may provide new options for adjunctive treatment of acute inflammation.

Chloral Hydrate Treatment Induced Apoptosis of Macrophages via Fas Signaling Pathway

PubMed Central

Cai, Jun; Peng, Yanxia; Chen, Ting; Liao, Huanjin; Zhang, Lifang; Chen, Qiuhua; He, Yiming; Wu, Ping; Xie, Tong; Pan, Qingjun

2016-01-01

Background There are recent reports on several anesthetics that have anti-inflammatory and anti-infective effects apart from their uses for pain relief and muscle relaxation. Chloral hydrate is a clinical anesthetic drug and sedative that has also been reported to attenuate inflammatory response, but the mechanisms are not clearly understood. Material/Methods This study investigated the effect of chloral hydrate treatment on the apoptosis of macrophages and explored the underlying mechanisms. RAW264.7 macrophages were treated with various concentrations of chloral hydrate for various lengths of time. Morphological changes were observed under a light microscope and apoptosis was detected with annexin-V-FITC/PI double-staining assay, Hochest 33258 and DNA ladder assay, the expression of Fas/FasL was detected with a flow cytometer, and the Fas signaling pathway was assessed by Western blotting. Results The results showed that chloral hydrate treatment induced the morphology of RAW264.7 macrophages to change shape from typical fusiform to round in a concentration- and time-dependent manner, and was finally suspended in the supernatant. For the induction of apoptosis, chloral hydrate treatment induced the apoptosis of RAW264.7 macrophages from early-to-late stage apoptosis in a concentration- and time-dependent manner. For the mechanism, chloral hydrate treatment induced higher expression of Fas on RAW264.7 macrophages, and was also associated with changes in the expression of proteins involved in Fas signaling pathways. Conclusions Chloral hydrate treatment can induce the apoptosis of RAW264.7 macrophages through the Fas signaling pathway, which may provide new options for adjunctive treatment of acute inflammation. PMID:27941708

Changes in membrane lipids drive increased endocytosis following Fas ligation.

PubMed

Degli Esposti, Mauro; Matarrese, Paola; Tinari, Antonella; Longo, Agostina; Recalchi, Serena; Khosravi-Far, Roya; Malorni, Walter; Misasi, Roberta; Garofalo, Tina; Sorice, Maurizio

2017-05-01

Once activated, some surface receptors promote membrane movements that open new portals of endocytosis, in part to facilitate the internalization of their activated complexes. The prototypic death receptor Fas (CD95/Apo1) promotes a wave of enhanced endocytosis that induces a transient intermixing of endosomes with mitochondria in cells that require mitochondria to amplify death signaling. This initiates a global alteration in membrane traffic that originates from changes in key membrane lipids occurring in the endoplasmic reticulum (ER). We have focused the current study on specific lipid changes occurring early after Fas ligation. We analyzed the interaction between endosomes and mitochondria in Jurkat T cells by nanospray-Time-of-flight (ToF) Mass Spectrometry. Immediately after Fas ligation, we found a transient wave of lipid changes that drives a subpopulation of early endosomes to merge with mitochondria. The earliest event appears to be a decrease of phosphatidylcholine (PC), linked to a metabolic switch enhancing phosphatidylinositol (PI) and phosphoinositides, which are crucial for the formation of vacuolar membranes and endocytosis. Lipid changes occur independently of caspase activation and appear to be exacerbated by caspase inhibition. Conversely, inhibition or compensation of PC deficiency attenuates endocytosis, endosome-mitochondria mixing and the induction of cell death. Deficiency of receptor interacting protein, RIP, also limits the specific changes in membrane lipids that are induced by Fas activation, with parallel reduction of endocytosis. Thus, Fas activation rapidly changes the interconversion of PC and PI, which then drives enhanced endocytosis, thus likely propagating death signaling from the cell surface to mitochondria and other organelles.

78 FR 11677 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Apache-Sitgreaves...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-12186; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Apache-Sitgreaves National Forests.... ACTION: Notice. SUMMARY: The U.S. Department of Agriculture (USDA), Forest Service, Apache-Sitgreaves...

Development and Preliminary Application of Multi-channel Agricultural Science and Technology Consulting Service U Disk

NASA Astrophysics Data System (ADS)

Yu, W. S.; Luo, C. S.; Wei, Q. F.; Zheng, Y. M.; Cao, C. Z.

2017-12-01

To deal with the “last kilometer” problem during the agricultural science and technology information service, the USB flash disk “Zixuntong”, which integrated five major consulting channels, i.e., telephone consultation, mutual video, message consultation, online customer service and QQ group was developed on the bases of capital experts and date resources. Since the products have the computer and telephone USB interface and are combined with localized information resources, users can obtain useful information on any terminal without the restriction of network. Meanwhile, the cartoon appearance make it friendly and attractive to people. The USB flash disk was used to provide agricultural expert consulting services and obtained a good preliminary application achievement. Finally, we concluded the creative application of USB flash disk in agricultural consulting services and prospected the future development direction of agricultural mobile consultation.

Illinois Occupational Skill Standards: Agricultural Machinery Service Technician.

ERIC Educational Resources Information Center

Illinois Occupational Skill Standards and Credentialing Council, Carbondale.

These Illinois skill standards for agriculture machinery service technician are intended to serve as a guide to workforce preparation program providers as they define content for their programs and to employers as they establish the skills and standards necessary for job acquisition. They could also serve as a mechanism for communication among…

Proteases in Fas-mediated apoptosis.

PubMed

Zhivotovsky, B; Burgess, D H; Schlegel, J; Pörn, M I; Vanags, D; Orrenius, S

1997-01-01

Involvement of a unique family of cysteine proteases in the multistep apoptotic process has been documented. Cloning of several mammalian genes identifies some components of this cellular response. However, it is currently unclear which protease plays a role as a signal and/or effector of apoptosis. We summarize contributions to the data concerning proteases in Fas-mediated apoptosis.

Valuing tradeoffs between agricultural production and ecosystem services in the Heihe River Basin

NASA Astrophysics Data System (ADS)

Li, Z.; Deng, X.; Wu, F.

2017-12-01

Ecosystem services are faced with multiple stress from complex driving factors, such as climate change and human interventions. The Heihe River Basin (HRB), as the second largest inland river basin in China, is a typical semi-arid and arid region with fragile and sensitive ecological environment. For the past decades, agricultural production activities in the basin has affected ecosystem services in different degrees, leading to complex relations among "water-land-climate-ecology-human", in which hydrological process and water resource management is the key. In this context, managing trade-offs among water uses in the river basin to sustain multiple ecosystem services is crucial for healthy ecosystem and sustainable socioeconomic development. In this study, we analyze the trade-offs between different water uses in agricultural production and key ecosystem services in the HRB by applying production frontier analysis, with the aim to explore the potential for managing them. This method traces out joint production frontiers showing the combinations of ecosystem services and agricultural production that can be generated in a given area, and it deals with the economic problem of the allocation of scarce water resources under presumed objective, which aims to highlight synergies and reduce trade-offs between alternative water uses. Thus, management schemes that targets to both sustain agricultural production and increase the provision of key ecosystem services have to consider not only the technological or biological nature of interrelationships, but also the economic interdependencies among them.

76 FR 75519 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

... it displays a currently valid OMB control number. Foreign Agricultural Service Title: Sugar Imported for Exports as Refined Sugar or as a Sugar- Containing Product, or Used in Production of Certain... authorizes the Foreign Agricultural Service (FAS) to issue import licenses to enter raw cane sugar exempt...

77 FR 39506 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Tongass National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-10467; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Tongass National Forest, Craig Ranger... of Agriculture (USDA), Forest Service, Tongass National Forest, has completed an inventory of human...

77 FR 68824 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Tongass National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11514; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Tongass National Forest, Juneau, AK..., Interior. ACTION: Notice. SUMMARY: The U.S. Department of Agriculture (USDA), Forest Service, Tongass...

77 FR 57113 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Arapaho and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11058; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Arapaho and Roosevelt National Forest...: Notice. SUMMARY: The U.S. Department of Agriculture (USDA), Forest Service, Arapaho and Roosevelt...

LncRNA FAS-AS1 promotes the degradation of extracellular matrix of cartilage in osteoarthritis.

PubMed

Zhu, J-K; He, T-D; Wei, Z-X; Wang, Y-M

2018-05-01

To investigate the expression of long non-coding RNA (lncRNA) FAS-AS1 in osteoarthritis cartilage and to explore its effect on articular cartilage cells. A total of 20 tissue samples of primary knee joint osteoarthritis and 20 tissue samples of knee joint cartilage after traumatic amputation were collected. Fluorescence quantitative polymerase chain reaction (PCR) was performed to detect the expression of FAS-AS1, MMP1, MMP13, and COL2A1 in cartilage. FAS-AS1 small interfering RNA (siRNA) was transfected to chondrocytes transiently to observe its effects on proliferation, apoptosis of chondrocytes, and the expressions of MMP1, MMP13, and COL2A1. The expressions of FAS-AS1, MMP1, and MMP13 in osteoarthritis tissues increased significantly, while COL2A1 presented a low expression. Reducing the expression of FAS-AS1 inhibited cell apoptosis and promote cell proliferation. Additionally, in vitro experiments showed that low expression of FAS-AS1 decreased the expressions of MMP1 and MMP13, but increased the expression of COL2A1. The expression of FAS-AS1 was increased in osteoarthritis, and FAS-AS1 could be involved in the development of the disease by regulating the proliferation, apoptosis of chondrocytes and promoting the degradation of extracellular matrix.

Transfection of apoptosis related gene Fas ligand in human hepatocellular carcinoma cells and its significance in apoptosis

PubMed Central

Chen, Jun; Su, Xian-Shi; Jiang, Yong-Fang; Gong, Guo-Zhong; Zheng, Yu-Huang; Li, Gui-Yuan

2005-01-01

AIM: To evaluate the expression of apoptosis related gene Fas ligand (FasL) in human hepatocellular carcinoma (HCC) cells HepG2 and its significance in apoptosis. METHODS: Levels of soluble Fas ligand (sFasL) in a group of patients with hepatitis B virus (HBV)-induced chronic hepatitis, HBV-positive liver cirrhosis and HCC were evaluated. In a further study, the recombinant eukaryotic expression plasmid pcDNA3.1hisB-FasL was transfected into HCC cells HepG2 by lipofection, and then soluble FasL was examined in the supernatant of culture cells by EIA, FasL expression in HepG2 cells was detected by immuohistochemistry. After being stained by annexin V and propidium iodine, cells were passed through a flow cytometer and examined by a fluorescence microscope and a laser scanning microscope. RESULTS: The sFasL levels were significantly lower in patients with HCC when compared to the patients with hepatitis or liver cirrhosis. In comparison with untransfected cells, the soluble FasL could be detected in the supernatant of transfected cells. FasL was expressed on the membranes and cytoplasm of transfected cells. The apoptotic cell rate was 36.30% in transfected cells, and was 11.53% in untransfected cells. Moreover, the different stage of apoptotic cells could be distinguished by annexin V and propidium iodine staining. CONCLUSION: Fas ligand is an apoptotic pathway of HCC cells. PMID:15849828

Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.

PubMed

Liu, Weifeng; Ramagopal, Udupi; Cheng, Huiyong; Bonanno, Jeffrey B; Toro, Rafael; Bhosle, Rahul; Zhan, Chenyang; Almo, Steven C

2016-11-01

The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-Fas antibody-induced apoptosis and its signal transduction in human gastric carcinoma cell lines.

PubMed

Adachi, Keiko; Osaki, Mitsuhiko; Kase, Satoru; Takeda, Ami; Ito, Hisao

2003-09-01

The Fas-Fas ligand system is one of the factors involved in cell death signaling. Aberrations in the signaling pathways leading to Fas-mediated apoptosis in tumor cells have been reported in a variety of human malignant tumors. However, the Fas-mediated apoptotic pathway has not been sufficiently elucidated in human gastric carcinomas. We examined the apoptotic pathway induced by anti-Fas antibody using seven human gastric carcinoma cell lines. Apoptosis was induced in a delayed fashion and the apoptotic indices (AI) after 48 h were approximately 30-40% in MKN-45 and KATO-III cells, which both showed cleavage of the Bid protein and release of Cytochrome c from the mitochondria. Our data also demonstrated no significant relationship between the expressions of various apoptosis-related proteins and the sensitivity or resistance to anti-Fas antibody-induced apoptosis, as far as we examined. Furthermore, the apoptosis signal was inhibited by treatment with Caspase-9 and -3 inhibitors in MKN-45 and KATO-III. These findings suggest that anti-Fas antibody induced apoptosis through the type II signaling pathway in the human gastric carcinoma cell lines, MKN-45 and KATO-III.

78 FR 59953 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Coconino National...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-13882; PPWOCRADN0-PCU00RP14.R50000] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Coconino National.... ACTION: Notice. SUMMARY: The U.S. Department of Agriculture (USDA), Forest Service, Coconino National...

Apoptosis in Acute Shigellosis Is Associated with Increased Production of Fas/Fas Ligand, Perforin, Caspase-1, and Caspase-3 but Reduced Production of Bcl-2 and Interleukin-2

PubMed Central

Raqib, Rubhana; Ekberg, Caroline; Sharkar, Protim; Bardhan, Pradip K.; Zychlinsky, Arturo; Sansonetti, Philippe J.; Andersson, Jan

2002-01-01

Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival. PMID:12011015

MECHANICAL POWER TRANSFER SYSTEMS. AGRICULTURAL MACHINERY-SERVICE OCCUPATIONS, MODULE NUMBER 8.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

ONE OF A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY-LEVEL STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT COMPETENCY IN UNDERSTANDING AND APPLYING THE PRINCIPLES OF MECHANICAL POWER TRANSMISSION IN AGRICULTURAL…

Single-Nucleotide Polymorphisms of FAS and FASL Genes and Risk of Idiopathic Aplastic Anemia.

PubMed

Rehman, Sadia; Saba, Nusrat; Naz, Madiha; Ahmed, Parvez; Munir, Saeeda; Sajjad, Sumaira; Tabassum, Sobia; Naseem, Lubna

2018-04-03

FAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities. Several single-nucleotide polymorphisms (SNPs) of FAS/FASL system can result in aberrant apoptosis, which can cause different cancers and autoimmune diseases. Aplastic anemia (AA) is an autoimmune dysfunction characterized by peripheral blood pancytopenia associated with hypoplasia of bone marrow. The aim of this study was to screen Pakistani AA patients and controls for two Fas SNPs rs2234767 and rs1800682 and two FASLG SNPs rs763110 and rs5030772. Genotyping of 392 DNA samples was done by Tetra-ARMS polymerase chain reaction. Genotypic frequencies of Fas rs1800682 and FASLG rs5030772 showed significance difference in their distribution in both controls and patients, while Fas rs2234767 and FASLG rs763110 SNPs had no such difference. Carriers of rs1800682 AG+GG had a very odd ratio of 4.63, with 95% confidence interval (CI) of 3.01-7.11, while individuals with FASLG rs5030772 AG+GG were more common in controls than patients with OR 0.53 and 95% CI of 0.34-0.83. Cumulative effects of these SNPs were analyzed, and they showed almost similar trends; however, Fas rs2234767 and FASLG rs763110 genotypes in combination with Fas rs1800682 and FASLG rs5030772 demonstrated significant association. This study provided information that endorsed the involvement of FAS/FASL system SNPs in the pathogenesis of AA; further studies should be designed to understand the exact role of SNPs that can help in early diagnosis and treatment.

Anti-Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery.

PubMed

Shendi, Dalia; Albrecht, Dirk R; Jain, Anjana

2017-02-01

Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017. © 2016 Wiley Periodicals, Inc.

Ursodeoxycholyl Lysophosphatidylethanolamide Protects Against CD95/FAS-Induced Fulminant Hepatitis.

PubMed

Utaipan, Tanyarath; Otto, Ann-Christin; Gan-Schreier, Hongying; Chunglok, Warangkana; Pathil, Anita; Stremmel, Wolfgang; Chamulitrat, Walee

2017-08-01

Increased activation of CD95/Fas by Fas ligand in viral hepatitis and autoimmunity is involved in pathogenesis of fulminant hepatitis and liver failure. We designed a bile-acid phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE with LPE containing oleate at the sn-1) as a hepatoprotectant that was shown to protect against fulminant hepatitis induced by endotoxin. We herein further assessed the ability of UDCA-LPE to prevent death receptor CD95/Fas-induced fulminant hepatitis. C57BL/6 mice were intravenously administered with CD95/Fas agonistic monoclonal antibody (Jo-2) with or without 1 h pretreatment with 50 mg/kg UDCA-LPE. Jo-2 administration caused massive hepatocyte damage as seen by histology, and this was associated with a significant decrease in hepatic phosphatidylcholine (PC), lysoPC, and lysophosphatidylethanolamine levels. By histology, UDCA-LPE pretreatment improved hepatocyte damage and restored the loss of these phospholipids in part by a mechanism involving an inhibition of cytosolic phospholipaseA2 expression. Accordingly, Jo-2 treatment increased hepatic expression of cleaved caspase 8, caspase 3, and poly (ADP-Ribose) polymerase-1, and on the other hand decreased that of anti-apoptotic cellular FLICE-inhibitory protein. UDCA-LPE pretreatment was able to reverse all these changes. Moreover, UDCA-LPE attenuated inflammatory response by lowering the levels of Jo-2-induced proinflammatory cytokines TNF-α, IL-6, and IL-1β in liver and serum. UDCA-LPE was also able to decrease the levels of stimulated Th1/Th17 cytokines in Jo-2-primed isolated splenocytes. Taken together, UDCA-LPE exhibited potent anti-inflammatory effects against CD95/Fas-induced fulminant hepatitis.

Inorganic arsenic exposure increased expression of Fas and Bax gene in vivo and vitro.

PubMed

He, Yuefeng; Zhang, Ruobing; Xiaoxiao, Song; Li, Shang; Xinan, Wu; Huang, Dahai

2018-06-01

Accumulating evidences have shown that apoptosis plays an important role in mediating the therapeutic effects and toxicity of arsenic. Fas and Bax genes are critical regulatory genes for apoptosis. In this study, we investigated the association between levels of Fas and Bax expression and the three arsenic species (inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in vivo and vitro. Three arsenic species in urine were measured and levels of Fas and Bax expression were examined by the quantitative real-time PCR (qPCR) for all subjects. We found that Fas and Bax mRNA expression in the exposed group were significantly higher than that in the control group. The levels of gene expression were positively correlated with the concentrations of urinary iAs, MMA and DMA in all subjects. Sodium arsenite induced Fas and Bax mRNA expression, then MMA and DMA did not induce mRNA expression in MDA-MB-231 and XWLC-05 cells. The findings of the present study indicated that iAs, MMA, and DMA had different effects on expression of Bax and Fas gene. Copyright © 2017. Published by Elsevier B.V.

Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Husain, Zaheed; Department of Pathology, Harvard Medical School, Boston, MA; Almeciga, Ingrid

Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 {mu}M) in the presence of 0.1 mM H{sub 2}O{sub 2} demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60more » cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis.« less

Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome.

PubMed

Torre, Donato; Tambini, Roberto; Manfredi, Mariangela; Mangani, Valerio; Livi, Paola; Maldifassi, Viviana; Campi, Paolo; Speranza, Filippo

2003-04-01

Resolution of inflammation/infection involves removal of neutrophils and other inflammatory cells by the induction of apoptosis. Fas/Apo-1 is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form. In this study we investigated the role of circulating Fas/Apo-1 in patients with systemic inflammatory response syndrome (SIRS). We evaluated 57 critically ill patients, 34 with infectious SIRS (sepsis and septic shock), and 23 patients with noninfectious SIRS. Circulating Fas/Apo-1 was determined by a commercially available immunoassay. Our results clearly show that levels of Fas/Apo-1 were significantly elevated in patients with infectious and noninfectious SIRS (10.4 +/- 8.1 pg/mL, controls: 5.0 +/- 0.7 pg/mL; p < 0.0001). In addition, Fas/Apo-1 levels were not able in predicting in predicting poor outcome of patients with SIRS. In conclusion, these results show that increased levels of Fas/Apo-1 from patients with SIRS is a mechanism which contribute to inflammatory response through accumulation of neutrophils at sites of inflammation/infection.

Agricultural Extension: Farm Extension Services in Australia, Britain and the United States.

ERIC Educational Resources Information Center

Williams, Donald B.

By analyzing the scope and structure of agricultural extension services in Australia, Great Britain, and the United States, this work attempts to set guidelines for measuring progress and guiding extension efforts. Extension training, agricultural policy, and activities of national, international, state, and provincial bodies are examined. The…

The Pla Protease of Yersinia pestis Degrades Fas Ligand to Manipulate Host Cell Death and Inflammation

PubMed Central

Caulfield, Adam J.; Walker, Margaret E.; Gielda, Lindsay M.; Lathem, Wyndham W.

2014-01-01

SUMMARY Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis. The bacterial protease Pla contributes to disease progression and manipulation of host immunity, but the mechanisms by which this occurs are largely unknown. Here we show that Pla degrades the apoptotic signaling molecule Fas ligand (FasL) to prevent host cell apoptosis and inflammation. Wild-type Y. pestis, but not a Pla mutant (Δpla), degrades FasL, which results in decreased downstream caspase-3/7 activation and reduced apoptosis. Similarly, lungs of mice challenged with wild-type Y. pestis show reduced levels of FasL and activated caspase-3/7 compared to Δpla infection. Consistent with a role for FasL in regulating immune responses, Δpla infection results in aberrant pro-inflammatory cytokine levels. The loss of FasL or inhibition of caspase activity alters host inflammatory responses and enables enhanced Y. pestis outgrowth in the lungs. Thus, by degrading FasL, Y. pestis manipulates host cell death pathways to facilitate infection. PMID:24721571

[Gene expression of H-FABP and FAS and its clinicopathological significance in breast infiltrating ductal carcinoma].

PubMed

Li, Hua; Lü, Qing; Xue, Hui; Dong, Li-hua; Yang, Hui-jun

2008-07-01

To detect the expression of Heart or Muscle Fatty acid binding protein (H-FABP) and fatty acid synthase (FAS) in human breast cancer cells. The expression levels of FAS and H-FABP in 81 ductal infiltrating carcinoma (DIC) were detected by RT-PCR, immunohistochemistry and Western blot analysis. The possible associations of the expression of the two proteins with major clinicopathological factors were analyzed. The expression of both H-FABP and FAS increased in DIC cells than in adjacent normal cells. But less H-FABP and FAS were found in grade III DIC than in grade I and grade II DIC (P < 0.05). There was a positive correlation between the expression of H-FABP and FAS. No correlations between the expressions of two genes with other clinicopathological factors were found. The higher expression of H-FABP in grade I and II DIC suggests an early increased response to the over-expression of FAS. The parallel increase of H-FABP and FAS expressions marks increased breast cancer risk.

The Potentials of Fas Receptors and Ligands in Monitoring HIV-1 Disease in Children in Yaoundé, Cameroon.

PubMed

Ikomey, G; Assoumou, M-C Okomo; Atashili, J; Mesembe, M; Mukwele, B; Lyonga, E; Eyoh, A; Kafando, A; Ndumbe, P M

2016-09-01

Difficulties in systematically monitoring HIV viral load in resource-limited settings prompt the search for alternate approaches. The authors aimed at assessing the correlation between the plasma levels of soluble forms of Fas receptors (Fas) and Fas ligands (FasL) with standard indicators of HIV disease progression in children. Twenty-two HIV-1-positive children were enrolled in Yaounde. CD4 counts, CD4% counts, plasma levels of Fas, FasL, and HIV-1 RNA levels were assayed. The correlation coefficients (P values) between FasL levels and each of HIV-1 viral load, CD4 counts, and CD4% were, respectively, .56 (.01), -.29 (.18), and .30 (.18). On the other hand, the respective correlation coefficients (P values) with Fas levels were .12 (.60), -.30 (.18), and -.29 (.19). The significant correlation between levels of HIV-1 viral load and FasL suggests that the latter needs to be further studied as a potential biomarker to monitor HIV-1 disease progression in children in resource-limited setting. © The Author(s) 2013.

Prominent dominant negative effect of a mutant Fas molecule lacking death domain on cell-mediated induction of apoptosis.

PubMed

Yokota, Aya; Takeuchi, Emiko; Iizuka, Misao; Ikegami, Yuko; Takayama, Hajime; Shinohara, Nobukata

2005-01-01

Using a panel of transfectant B lymphoma cells expressing varying amounts of the mutant Fas together with the endogenous wild type Fas, semi-quantitative studies on the dominant negative effect of a murine mutant Fas molecule lacking death domain were carried out. In anti-Fas antibody-mediated induction of apoptosis, the mutant molecules exerted significant dominant-negative effect only when their expression level was comparable to or higher than that of wild type molecules, or when exposed to low amounts of the antibody. The inhibitory effect was accompanied by the failure in DISC formation in spite of Fas aggregation. When they were subjected to T cell-mediated Fas-based induction of apoptosis, however, the dominant negative effect was prominent such that the expression of even a small amount of the mutant molecules resulted in significant inhibition. Such a strong inhibitory effect explains the dominant phenotype of this type of mutant Fas molecules in ALPS heterozygous patients and also implies that the physiological effectors for Fas in vivo are cells, i.e., FasL-expressing activated T cells.

GUIDELINES FOR STATE VOCATIONAL AGRICULTURE CURRICULUM MATERIALS SERVICES, A RESEARCH REPORT OF A GRADUATE STUDY. RESEARCH SERIES IN AGRICULTURAL EDUCATION.

ERIC Educational Resources Information Center

RIDENOUR, HARLAN E.; WOODIN, RALPH J.

PROBLEMS OF VOCATIONAL AGRICULTURE TEACHERS IN KEEPING ABREAST OF TECHNICAL KNOWLEDGE AND OBTAINING OR PREPARING MATERIALS STRUCTURED IN LOGICAL SEQUENCE FOR TEACHING PROMPTED A STUDY TO DEVELOP GUIDELINES FOR ORGANIZING AND OPERATING A STATEWIDE VOCATIONAL AGRICULTURE CURRICULUM MATERIALS SERVICE. A SURVEY OF 48 STATE DIRECTORS AND 48 STATE…

7 CFR 20.2 - Administration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Administration. 20.2 Section 20.2 Agriculture Office of the Secretary of Agriculture EXPORT SALES REPORTING REQUIREMENTS § 20.2 Administration. The regulations of this part will be administered by the Foreign Agricultural Service (FAS) under the general...

76 FR 5778 - Public Availability of the Department of Agriculture FY 2010 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

... DEPARTMENT OF AGRICULTURE Public Availability of the Department of Agriculture FY 2010 Service... the Consolidated Appropriations Act of 2010 (Pub. L. 111-117), Department of Agriculture is publishing...-inventories-guidance-11052010.pdf . Department of Agriculture has posted its inventory and a summary of the...

Effective Teaching for FAS & FAE Children.

ERIC Educational Resources Information Center

Root, Pam

This paper discusses the importance of teaching social skills to children with Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Effect (FAE) and the interrelationship between social skills and academic improvement. Goals and techniques for teaching social skills are identified, including: (1) improving the skill of compliance by setting reasonable…

Butyric Acid-Induced T-Cell Apoptosis Is Mediated by Caspase-8 and -9 Activation in a Fas-Independent Manner

PubMed Central

Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu; Fukushima, Kazuo

2001-01-01

Our previous study demonstrated that butyric acid, an extracellular metabolite of periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat cells. In this study, we examined whether CD95 ligand-receptor interaction is involved in butyric acid-induced T-cell apoptosis. Flow cytometry analysis indicated that expression of Fas in Jurkat and T cells from peripheral blood mononuclear cells was not affected by butyric acid treatment. Furthermore, the expression of Fas and FasL protein in Western blotting was not affected by butyric acid treatment. Coincubation with blocking anti-Fas antibodies prevented Fas-induced apoptosis but not butyric acid-induced apoptosis. Anti-FasL antibodies also did not prevent butyric acid-induced apoptosis at any dose examined. Although cytotoxic anti-Fas antibody affected butyric acid-induced apoptosis, a synergistic effect was not seen. Time-dependent activation of caspase-8 and -9 was recognized in butyric acid- as well as Fas-mediated apoptosis. IETD-CHO and LEHD-CHO, specific inhibitors of caspase-8 and -9, respectively, completely blocked Fas-mediated apoptosis and partially prevented butyric acid-induced apoptosis. These results suggest that the Fas-FasL interaction is not involved in butyric acid-induced apoptosis and that caspase-8 and -9-dependent apoptosis plays an important role in butyric acid-induced apoptosis, as well as Fas-induced apoptosis. PMID:11238216

77 FR 51562 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-24

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-10923; 2200-1100-665] Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service, Coconino National.... Department of Agriculture (USDA), Forest Service, Coconino National Forest, in consultation with the...

77 FR 52055 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11022; 2200-1100-665] Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service, Coconino National.... Department of Agriculture (USDA), Forest Service, Coconino National Forest, in consultation with the...

Gene therapy for human ovarian cancer cells using efficient expression of Fas gene combined with γδT cells.

PubMed

Lin, Jiajing; Zeng, Dingyuan; He, Hongying; Tan, Guangping; Lan, Ying; Jiang, Fuyan; Sheng, Shuting

2017-10-01

Low tissue specificity and efficiency of exogenous gene expression are the two major obstacles in tumor‑targeted gene therapy. The Fas cell surface death receptor (Fas)/Fas ligand pathway is one of the primary pathways responsible for the regulation of cell apoptosis. The aim of the present study was to explore whether the regulation of tumor specific promoters and a two‑step transcriptional amplification system (TSTA) assured efficient, targeted expression of their downstream Fas gene in human ovarian cancer cells, and to assess the killing effect of γδT cells on these cells with high Fas expression. Three shuttle plasmids containing different control elements of the human telomerase reverse transcriptase (hTERT) promoter and/or TSTA were constructed and packaged into adenovirus 5 (Ad5) vectors for the expression of exogenous Fas gene. The human ovarian cancer cell line SKOV3 and a control human embryonic lung fibroblast cell line were transfected with Ad5‑hTERT‑Fas or Ad5‑hTERT‑TSTA‑Fas. Fas mRNA and protein expression were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. γδT lymphocytes were isolated, cultured and mixed at different ratios with SKOV3 cells with Fas expression in order to assess the killing effect of γδT cells. hTERT promoter induced the specific expression of FAS gene in SKOV3 cells, and the TSTA strategy increased FAS expression by 14.2‑fold. The killing effect of γδT cells increased with the expression level of Fas and the effector‑target cell ratio. The killing rate for SKOV3 cells with high FAS expression was 72.5% at an effector‑target cell ratio of 40:1. The regulators of hTERT promoter and TSTA assure the efficient and targeted expression of their downstream Fas gene in SKOV3 cells. The killing effect of γδT cells for ovarian cancer cells with relatively high Fas expression was improved.

77 FR 68821 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11492; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis National Forests... Agriculture (USDA), Forest Service, Ozark-St. Francis National Forests has completed an inventory of human...

78 FR 2436 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11885; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis National Forests... U.S. Department of Agriculture (USDA), Forest Service, Ozark-St. Francis National Forests has...

77 FR 68822 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11491: 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis National Forests... Agriculture (USDA), Forest Service, Ozark-St. Francis National Forests has completed an inventory of human...

77 FR 68819 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-11493; 2200-1100-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Ozark-St. Francis National Forests... Agriculture (USDA), Forest Service, Ozark-St. Francis National Forests has completed an inventory of human...

Improving Agricultural Productivity in Tonga through Ensuring Data Availability and Enhancing Agro-meteorological Services

NASA Astrophysics Data System (ADS)

Kim, K. H.

2015-12-01

The project was first conceived in the Global Framework for Climate Services Regional Consultation in the Cook Islands in March 2014. In this meeting, key officials from the Ministry of Agriculture and Food, Forests, and Fisheries and the Tonga Meteorological Services had a meeting with the APEC Climate Center scientists with the idea to collaborate on a joint project. The project evolved to include the following components: assessment of users' needs and capacities, development of an agricultural database, research on the core relationships between agriculture and climate through modeling and field trials, and the development and delivery of agro-meteorological services. Envisioned outputs include a 2-7 day warning for pests and diseases, a suite of tools supporting decisions on planting dates and crop varieties, and other advisory services derived from seasonal climate forecasts. As one of the climate adaptation projects under its Pacific Island portfolio, the project will deliver urgent information services for Tongan agricultural growers and exporters. The project comes into greater importance and urgency, as the 2014 drought event resulted in the destruction of 80% of squash in Tonga, a main export crop from which the country derives foreign exchange earnings. Since 2014, some of the project achievements include the first agro-met data collection in Tonga, the development of an agricultural DB management system that houses archived agriculture data, and key meetings with stakeholders to ensure alignment of the project objectives and design with the interests of the Tongan government and other stakeholders. In addition, rigorous scientific research through modeling and field trials has been conducted to address the twin goals of supporting Tonga's economy as well as food security. Based on the findings from the research, tools will be developed to translate the science into knowledge that supports decisions on the farm scale.

Fas Ligand-Mediated Lysis of Self Bystander Targets by Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes

PubMed Central

Smyth, Mark J.; Krasovskis, Erika; Johnstone, Ricky W.

1998-01-01

Mouse cytotoxic T lymphocytes (CTL) reactive with a H-2Db-presented 9-mer peptide of the human papillomavirus type 16 protein E749-57 (RAHYNIVTF) were generated from the spleen cells of wild-type C57BL/6 (B6) or B6 perforin-deficient (B6.P0) mice. CD8+ B6 CTL displayed peptide-specific perforin- and Fas-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7), while CD8+ CTL from B6.P0 mice lysed RMA-E7 cells via Fas ligand (FasL) exclusively. Rapid and efficient lysis of syngeneic bystander B6 blasts or RMA cells by either B6 or B6.P0 Ag-activated CTL was mediated by a FasL-Fas mechanism. Fas-resistant bystanders were not lysed, nor were allogeneic Fas-sensitive C3H/HeJ (H-2k) or BALB/c (H-2d) bystander blasts. Interestingly, however, phorbol myristate acetate-ionomycin preactivation of B6.P0 effectors enabled lysis of allogeneic H-2k and H-2d bystanders even in the absence of antigenic stimulation. Lysis of syngeneic bystander cells was always FasL-Fas dependent and required effector-bystander contact and, in particular, an interaction between CTL LFA-1 and bystander ICAM-1. Thus, in the context of major histocompatibility complex class I molecule-peptide ligation of the T-cell receptors of CD8+ CTL, neighboring bystander cells that are syngeneic and Fas sensitive and express the adhesion molecule ICAM-1 are potential targets of CTL attack. PMID:9621057

NUOnet, a Data Network Initiative Led by the USDA Agricultural Research Service

USDA-ARS?s Scientific Manuscript database

The USDA Agricultural Research Service is launching a new effort to gather and use big data to solve agricultural issues that face our nation. The Nutrient Use and Outcome network (NUOnet) is a part of this effort. NUOnet invites members of the Tri-Societies to contribute to the NUOnet vision of “...

FERTILIZERS SALES AND SERVICE. AGRICULTURAL SUPPLY - SALES AND SERVICE OCCUPATIONS, MODULE NUMBER 9.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

THE PURPOSE OF THIS GUIDE IS TO ASSIST TEACHERS IN PREPARING HIGH SCHOOL AND POST-HIGH SCHOOL STUDENTS FOR AGRICULTURAL SUPPLY OCCUPATIONS. ONE OF A SERIES, THIS MODULE WAS DEVELOPED ON THE BASIS OF STATE STUDIES BY A NATIONAL TASK FORCE. THE SPECIFIC OBJECTIVE IS TO PREPARE STUDENTS FOR ENTRY AND ADVANCEMENT IN FERTILIZER SALES AND SERVICE.…

Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells.

PubMed

English, William R; Ireland-Zecchini, Heather; Baker, Andrew H; Littlewood, Trevor D; Bennett, Martin R; Murphy, Gillian

2018-01-01

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis

Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

PubMed Central

Ireland-Zecchini, Heather; Baker, Andrew H.; Littlewood, Trevor D.; Bennett, Martin R.; Murphy, Gillian

2018-01-01

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis

FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation

PubMed Central

Libera, Laura; Boari, Nicola; Mortini, Pietro; Bellipanni, Gianfranco; Giordano, Antonio; Cotelli, Franco; Riva, Paola

2014-01-01

Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset. PMID:25071022

FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation.

PubMed

Ferrari, Luca; Pistocchi, Anna; Libera, Laura; Boari, Nicola; Mortini, Pietro; Bellipanni, Gianfranco; Giordano, Antonio; Cotelli, Franco; Riva, Paola

2014-07-30

Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset.

An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers

PubMed Central

Chakrabandhu, Krittalak; Huault, Sébastien; Durivault, Jérôme; Lang, Kévin; Ta Ngoc, Ly; Bole, Angelique; Doma, Eszter; Dérijard, Benoit; Gérard, Jean-Pierre; Pierres, Michel; Hueber, Anne-Odile

2016-01-01

Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive “Fas apoptosis” to “Fas multisignals” paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs) and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases. PMID:26942442

Complete loss of Fas ligand gene causes massive lymphoproliferation and early death, indicating a residual activity of gld allele.

PubMed

Karray, Saoussen; Kress, Chantal; Cuvellier, Sylvain; Hue-Beauvais, Catherine; Damotte, Diane; Babinet, Charles; Lévi-Strauss, Matthieu

2004-02-15

To investigate the in vivo function of Fas ligand (FasL), we produced a mouse strain with a FasL gene flanked by loxP sequences. Mice with homozygous floxed FasL gene showed no obvious abnormalities. However, germline deletion of the FasL gene, obtained after mating with mice expressing ubiquitous Cre recombinase, resulted in an unexpectedly severe phenotype. FasL(-/-) mice exhibited an extreme splenomegaly and lymphadenopathy associated with lymphocytic infiltration into multiple organs and autoimmune disease. This severe phenotype led to the premature death at 4 mo of age of >50% of the homozygous mice. It stands in sharp contrast with the milder disease observed in gld (generalized lymphoproliferative disease) mice, indicating that the FasL allele of these mice encodes a protein still able to bind, albeit at a very low level, the Fas receptor.

Expression of Fas, FasL, caspase-8 and other factors of the extrinsic apoptotic pathway during the onset of interdigital tissue elimination.

PubMed

Svandova, E Budisova; Vesela, B; Lesot, H; Poliard, A; Matalova, E

2017-04-01

Elimination of the interdigital web is considered to be the classical model for assessing apoptosis. So far, most of the molecules described in the process have been connected to the intrinsic (mitochondrial) pathway. The extrinsic (receptor mediated) apoptotic pathway has been rather neglected, although it is important in development, immunomodulation and cancer therapy. This work aimed to investigate factors of the extrinsic apoptotic machinery during interdigital regression with a focus on three crucial initiators: Fas, Fas ligand and caspase-8. Immunofluorescent analysis of mouse forelimb histological sections revealed abundant expression of these molecules prior to digit separation. Subsequent PCR Array analyses indicated the expression of several markers engaged in the extrinsic pathway. Between embryonic days 11 and 13, statistically significant increases in the expression of Fas and caspase-8 were observed, along with other molecules involved in the extrinsic apoptotic pathway such as Dapk1, Traf3, Tnsf12, Tnfrsf1A and Ripk1. These results demonstrate for the first time the presence of extrinsic apoptotic components in mouse limb development and indicate novel candidates in the molecular network accompanying the regression of interdigital tissue during digitalisation.

The Value of SMAP Soil Moisture Observations For Agricultural Applications

NASA Astrophysics Data System (ADS)

Mladenova, I. E.; Bolten, J. D.; Crow, W.; Reynolds, C. A.

2017-12-01

Knowledge of the amount of soil moisture (SM) in the root zone (RZ) is critical source of information for crop analysts and agricultural agencies as it controls crop development and crop condition changes and can largely impact end-of-season yield. Foreign Agricultural Services (FAS), a subdivision of U.S. Department of Agriculture (USDA) that is in charge with providing information on current and expected global crop supply and demand estimates, has been relying on RZSM estimates generated by the modified two-layer Palmer model, which has been enhanced to allow the assimilation of satellite-based soil moisture data. Generally the accuracy of model-based soil moisture estimates is dependent on the precision of the forcing data that drives the model and more specifically, the accuracy of the precipitation data. Data assimilation gives the opportunity to correct for such precipitation-related inaccuracies and enhance the quality of the model estimates. Here we demonstrate the value of ingesting passive-based soil moisture observations derived from the Soil Moisture Active Passive (SMAP) mission. In terms of agriculture, general understanding is that the change in soil moisture conditions precede the change in vegetation status, suggesting that soil moisture can be used as an early indicator of expected crop conditions. Therefore, we assess the accuracy of the SMAP enhanced Palmer model by examining the lag rank cross-correlation coefficient between the model generated soil moisture observations and the Normalized Difference Vegetation Index (NDVI).

COURSE OUTLINE FOR AGRICULTURAL SUPPLY - SALES AND SERVICE OCCUPATIONS.

ERIC Educational Resources Information Center

BECKER, WILLIAM; LINTNER, J.H.

TITLES OF MODULES, PURPOSES, TIME AND SUPPORTING EDUCATIONAL REQUIREMENTS, AND OPERATIONAL DETAILS OF A COURSE ARE GIVEN IN THIS PUBLICATION DESIGNED TO ASSIST STATE AND LOCAL VOCATIONAL EDUCATION LEADERS IN DEVELOPING PROGRAMS TO PREPARE HIGH SCHOOL STUDENTS FOR ENTRY AND ADVANCEMENT IN BUSINESSES WHICH SELL AGRICULTURAL SUPPLIES AND SERVICES TO…

78 FR 34125 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, San Juan National...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-13011; PPWOCRADN0-PCU00RP14.R50000] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, San Juan National... of Agriculture (USDA), Forest Service, San Juan National Forest has completed an inventory of human...

78 FR 34131 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-13010; PPWOCRADN0-PCU00RP14.R50000] Notice of Intent To Repatriate Cultural Items: U.S. Department of Agriculture, Forest Service...: The U.S. Department of Agriculture (USDA), Forest Service, San Juan National Forest, in consultation...

Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.

PubMed

Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T; Lucas, Julie A; Rabacal, Whitney A; Croker, Byron P; Zong, Xiao-Hua; Stanley, E Richard; Kelley, Vicki R

2008-11-15

Sunlight (UVB) triggers cutaneous lupus erythematosus (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø)-mediated mechanism in MRL-Fas(lpr) mice. By constructing mutant MRL-Fas(lpr) strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex vivo gene transfer to deliver CSF-1 intradermally, we determined that CSF-1 induces CLE in lupus-susceptible MRL-Fas(lpr) mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Møs, apoptosis in the skin, and CLE in MRL-Fas(lpr), but not in CSF-1-deficient MRL-Fas(lpr) mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Møs that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Fas(lpr) but not lupus-resistant BALB/c mice. Taken together, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE.

Serological levels of apoptotic bodies, sFAS and TNF in lupus erythematosus.

PubMed

Alecu, M; Coman, G; Alecu, S

In our study we have investigated the presence of apoptotic bodies, soluble FAS receptor and TNF (tumor necrosis factor) in three clinical forms of lupus erythematosus. Determinations were performed in attack period of: systemic lupus erythematosus (SLE) for 20 patients, 20 patients with subacute cutaneous lupus erythematosus (SCLE), 20 patients with chronic discoid lupus erythematosus (DLE). Determinations were performed by ELISA (for apoptotic bodies, kit Boehringer, normal values 400-800 mU), (for sFAS, kit R&D Systems, normal values 4500-17000 pg/ml) (for TNF, ELISA kit R&D Systems, normal values 0.4-3.6 pg/ml). Results in SLE: apoptotic bodies were increased in 16 cases (980-1030); sFAS in 18 cases (17000-24000 pg/ml) TNF was increased in all 20 cases (40-140 pg/ml). In SCLE with multiple cutaneous lesions and without internal organs disturbance the apoptotic bodies were increased in 10 cases (960-1030 pg/ml), sFAS in 9 cases (17000-22000 pg/ml), and TNF alpha in 9 cases. In DLE, apoptotic bodies were increased in 2 patients (980-1010 pg/ml), sFAS in 3 patients (17000-20000 pg/ml) and TNF in 2 patients (20-40 pg/mil). Investigated values were slightly correlated with immune parameters (anti dsDNA antibodies), but they were correlated with the presence of renal disturbances or extension of cutaneous lesions. We consider that the presence of increased apoptotic bodies as a result of peripheral mononuclear cells apoptosis appear as a nauto-limiting mechanism in a pathological immune response. The increase of sFAS in lupus patients serum might be interpreted as an alteration of apoptosis respectively a deficit in apoptosis which has as a first consequence the persistence of B and T lymphocytes, activated, in the pathogen immune response.

A novel splice variant of the Fas gene in patients with cutaneous T-cell lymphoma.

PubMed

van Doorn, Remco; Dijkman, Remco; Vermeer, Maarten H; Starink, Theo M; Willemze, Rein; Tensen, Cornelis P

2002-10-01

Defective apoptosis signaling has been implicated in the pathogenesis of primary cutaneous T-cell lymphomas (CTCLs), a group of malignancies derived from skin-homing T cells. An important mediator of apoptosis in T cells is the Fas receptor. We identified a novel splice variant of the Fas gene that displays retention of intron 5 and encodes a dysfunctional Fas protein in 13 of 22 patients (59%) in both early and advanced CTCL. Impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of CTCL by allowing continued clonal expansion of activated T cells and by reducing susceptibility to antitumor immune responses.

76 FR 14068 - Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Sequoia National...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... DEPARTMENT OF THE INTERIOR National Park Service [2253-665] Notice of Inventory Completion: U.S. Department of Agriculture, Forest Service, Sequoia National Forest, Porterville, CA AGENCY: National Park... and associated funerary objects in the possession and control of the U.S. Department of Agriculture...

Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis.

PubMed

Mou, Haiwei; Moore, Jill; Malonia, Sunil K; Li, Yingxiang; Ozata, Deniz M; Hough, Soren; Song, Chun-Qing; Smith, Jordan L; Fischer, Andrew; Weng, Zhiping; Green, Michael R; Xue, Wen

2017-04-04

Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras , indicating the existence of Kras -independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras -independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras -expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles' heel in tumors initiated by oncogenic Kras.

NF-κB Regulates Caspase-4 Expression and Sensitizes Neuroblastoma Cells to Fas-Induced Apoptosis

PubMed Central

Yang, Hai-Jie; Wang, Mian; Wang, Lei; Cheng, Bin-Feng; Lin, Xiao-Yu; Feng, Zhi-Wei

2015-01-01

Found in neurons and neuroblastoma cells, Fas-induced apoptosis and accompanied activation of NF-κB signaling were thought to be associated with neurodegenerative diseases. However, the detailed functions of NF-κB activation in Fas killing and the effect of NF-κB activation on its downstream events remain unclear. Here, we demonstrated that agonistic Fas antibody induces cell death in a dose-dependent way and NF-κB signaling is activated as well, in neuroblastoma cells SH-EP1. Unexpectedly, NF-κB activation was shown to be pro-apoptotic, as suggested by the reduction of Fas-induced cell death with either a dominant negative form of IκBα (DN-IκBα) or an IκB kinase-specific inhibitor. To our interest, when analyzing downstream events of NF-κB signaling, we found that DN-IκBα only suppressed the expression of caspase-4, but not other caspases. Vice versa, enhancement of NF-κB activity by p65 (RelA) overexpression increased the expression of caspase-4 at both mRNA and protein levels. More directly, results from dual luciferase reporter assay demonstrated the regulation of caspase-4 promoter activity by NF-κB. When caspase-4 activity was blocked by its dominant negative (DN) form, Fas-induced cell death was substantially reduced. Consistently, the cleavage of PARP and caspase-3 induced by Fas was also reduced. In contrast, the cleavage of caspase-8 remained unaffected in caspase-4 DN cells, although caspase-8 inhibitor could rescue Fas-induced cell death. Collectively, these data suggest that caspase-4 activity is required for Fas-induced cell apoptosis and caspase-4 may act upstream of PARP and caspase-3 and downstream of caspase-8. Overall, we demonstrate that NF-κB can mediate Fas-induced apoptosis through caspase-4 protease, indicating that caspase-4 is a new mediator of NF-κB pro-apoptotic pathway in neuroblastoma cells. PMID:25695505

[Effect of total flavones from Cuscuta chinensis on expression of Fas/FasL, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion].

PubMed

Ma, Hong-Xia; You, Zhao-Ling; Wang, Xiao-Yun

2008-11-01

To explore the effect of total flavones from cuscuta chinensis (TFCC) on expression of Fas, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion. The model rats of bromocriptine during 6-8 d of pregnancy induced early abortion was established, adopting respectively herbs in high and low dosage and progesterone affect model rat and after 12 d, Immunohistochemical was applied to determine Fas, HB-EGF and PCNA in deciduas and placenta. Expression of PCNA on trophoblast and deciduas, HB-EGF on trophoblast, PR on deciduas in the model used Semen cuscutae flavonoid, proesterone and normal pregnacy, were significantlly higher than those of the pure model. Expression of Fas on trophoblast and deciduas in above four groups, were significantlly lower than those of the pure model. There were no expression of HB-EGF on deciduas. TFCC regulates the proliferation and apoptosis of the deciduas and cytotrophoblasts and prevents spontaneous abortions.

Overexpression of soluble Fas ligand following AAV gene therapy prevents retinal ganglion cell death in chronic and acute murine models of glaucoma

PubMed Central

Krishnan, Anitha; Fei, Fei; Jones, Alexander; Busto, Patricia; Marshak-Rothstein, Ann; Ksander, Bruce R.; Gregory-Ksander, Meredith

2016-01-01

Glaucoma is a multifactorial disease resulting in the death of retinal ganglion cells (RGCs) and irreversible blindness. Glaucoma-associated RGC cell death depends on the pro-apoptotic and proinflammatory activity of membrane-bound FasL (mFasL). In contrast to mFasL, the natural soluble FasL cleavage product (sFasL) inhibits mFasL-mediated apoptosis and inflammation and is therefore a mFasL antagonist. DBA/2J (D2) mice spontaneously develop glaucoma and predictably RGC destruction is exacerbated by expression of a mutated membrane-only FasL (mFasL) gene that lacks the extracellular cleavage site. Remarkably, one time intraocular adeno-associated virus-mediated gene delivery of sFasL (AAV2.sFasL) provides complete and sustained neuroprotection in both the chronic D2 and acute microbead-induced models of glaucoma, even in the presence of elevated intraocular pressure (IOP). This protection correlated with inhibition of glial activation, reduced production of TNFα, and decreased apoptosis of RGCs and loss of axons. These data indicate that cleavage of FasL under homeostatic conditions, and the ensuing release of sFasL, normally limits the neurodestructive activity of FasL. The data further support the notion that sFasL, and not mFasL, contributes to the immune privileged status of the eye. PMID:27849168

How agricultural multiple ecosystem services respond to socioeconomic factors in Mengyin County, China.

PubMed

Chen, Yajuan; Yu, Zhenrong; Li, Xuedong; Li, Pengyao

2018-07-15

Provisioning services have always been the main focus of agriculture, and which have led to a decline in biodiversity and have damaged a number of other services. Agriculture should contribute to current and future food security while producing multiple ecosystem services (ES). Restoration outcomes of multiple ES were affected by different socioeconomic drivers, thus a better understanding of how multiple ES respond to socioeconomic drivers can help to restore multiple ES. This paper used rural people's perceptions of ES to quantify and map ecosystem service obtainment and demand in the Mengyin County, China. An integrative index of multiple ecosystem services (IMES) was used to effectively aggregate the values of multiple ES. The threat categorization framework is designed to communicate the degree to which the adequate and sustainable provision of multiple ES is threatened, in order to prioritize conservation actions. The results revealed that 6 townships in the Mengyin County exhibited an excessive obtainment situation (demand is less than obtainment) of multiple ES; an insufficient obtainment situation (demand is greater than obtainment) of multiple ES was mainly situated in the northern part of Mengyin County. Overall, the current state of multiple ES across Mengyin County is classified as "Endangered" classification according to application of threat categorization framework. It is necessary to restructure and manage socioeconomic factors for multiple ES. At national level, the macro decision-making (controlling population density) and the mechanisms (attracting high-quality human resources into the rural) will play an important role in promoting multiple ES management, and it is necessary to provide 3 or more years of tailored educational resources for rural residents to advance multiple ES in agricultural landscape. Development of agricultural PES programs in China that enable farmers to profit from production ES is a sustainable strategy for increasing

Pin1-FADD interactions regulate Fas-mediated apoptosis in activated eosinophils#

PubMed Central

Oh, Jiyoung; Malter, James S.

2013-01-01

Abnormally long-lived eosinophils (Eos) are the major inflammatory component of allergic responses in the lungs of active asthmatics. Eos recruited to the airways after allergen exposure produce and respond to IL-5 and GM-CSF, enhancing their survival. Pro-survival signaling activates Pin1, a cis-trans peptidyl isomerase (PPIase) that binds to Bax and prevents it activation. How long-lived Eos, despite the continued presence of GM-CSF or IL-5, eventually undergo apoptosis to end allergic inflammation remains unclear. Here we show that Pin1 location, activity and protein interactions are jointly influenced by Fas and pro-survival cytokine IL-5. Fas signaling strongly induced the phosphorylation of FADD at Ser194 and Pin1 at Ser16 as well as their nuclear accumulation. Phospho-mimic Ser194Glu FADD mutants accelerated Eos apoptosis compared to WT or Ser194Ala mutants. Downstream of FADD phosphorylation, Caspase 8, 9 and 3 cleavage as well as Eos apoptosis induced by Fas were reduced by constitutively active Pin1 and enhanced by Pin1 inhibition. Pin1 was activated by IL-5 while simultaneous IL-5 and anti-Fas treatment modestly reduced PPIase activity but induced Pin1 to associate with FADD after its phosphorylation at Ser194. Mechanistically, Pin1 mediated isomerization facilitated the subsequent dephosphorylation of Ser194 FADD and maintenance of cytoplasmic location. In vivo activated bronchoalvelolar (BAL) Eos obtained after allergen challenge showed elevated survival and Pin1 activity that could be reversed by anti-Fas. Therefore, our data suggest that Pin1 is a critical link between FADD mediated cell death and IL-5 mediated pro-survival signaling. PMID:23606538

Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-kappaB-mediated expression in cultured human mesangial cells.

PubMed

Tsukinoki, Tomoko; Sugiyama, Hitoshi; Sunami, Reiko; Kobayashi, Mizuho; Onoda, Tetsuya; Maeshima, Yohei; Yamasaki, Yasushi; Makino, Hirofumi

2004-09-01

Fas ligand (FasL) is a well-known death factor; however, the role of FasL in the regulation of human glomerulonephritis remains unclear. We investigated the renal expression and localization of FasL in various forms of human glomerulonephritis by immunohistochemistry, utilizing confocal laser scanning microscopy. We further evaluated cytokine-induced FasL expression via nuclear factor (NF)kappaB in cultured human mesangial cells (HMC). The level of soluble FasL was measured by a specific enzyme-linked immunosorbent assay (ELISA). The frequency of glomerular FasL-positive cases was higher in lupus nephritis (37.9%) as compared with other forms of glomerulonephritis (8.7%). The glomerular FasL score in proliferative lupus nephritis was significantly higher than that in nonproliferative forms. Patients with a high apoptosis score, severe microhematuria, proteinuria, or decreased renal function had a high FasL score. Double immunolabelling demonstrated that the most prevalent phenotypes of FasL-positive cells were mesangial cells. In cultured HMC, interleukin (IL)1beta, lipopolysaccharide (LPS), or gamma interferon (IFN) upregulated membrane-bound FasL. IL1beta significantly, and LPS or gammaIFN weakly activated NFkappaB, but none of these agents activated NFkappaB/Rel-related nuclear factor of activated T cells (NFATc) or IFN regulatory factor-1. IL1beta-mediated NFkappaB was completely inhibited in the presence of lactacystin, a potent inhibitor of NFkappaB. Lactacystin-mediated inhibition of NFkappaB reduced FasL protein levels. Matrix metalloproteinase (MMP)-7, but not other MMPs (1, 2, 3, 8, or 9), significantly sensitized HMC to release soluble FasL after IL1beta stimulation. The results suggest that: (1) upregulation of mesangial FasL may contribute to the glomerular inflammation in proliferative lupus nephritis in vivo; (2) proinflammatory cytokines, in particular IL1beta, produced in nephritis can upregulate FasL via the transcription factor NFkappaB in HMC

Interferon-alpha and interferon-gamma modulate Fas-mediated apoptosis in mitomycin-C-resistant human Tenon's fibroblasts.

PubMed

Wang, Xiao Yang; Crowston, Jonathan G; White, Andrew J R; Zoellner, Hans; Healey, Paul R

2014-08-01

The aim of the study was to investigate, using a native mitomycin-C-resistant human Tenon's fibroblast cell line, the possibility that interferon-alpha and gamma could be used with Fas agonists as an alternative anti-fibrotic strategy to mitomycin-C in trabeculectomy. A clinically resistant and in vitro verified mitomycin-C-resistant human Tenon's fibroblast cell line was pretreated with interferon-alpha and interferon-gamma for 48 h before stimulation with an agonistic Fas antibody (CH11) for 2 days to induce cell death. Cell death assays were undertaken. Changes in apoptosis-related proteins were determined by flow cytometry and Western blot. Pretreatment with interferon-alpha or interferon-gamma for 48 h increased Fas, Fas-associated protein with death domain and caspase-8 expression. Protein expression was further increased by combined exposure to interferon-alpha and gamma. Pretreatment with cytokines had no effect on Fas-L and Bcl-2. Interferon-alpha alone did not change the rate of induced cell death. A combination of interferon-alpha and gamma synergistically increased the sensitivity of mitomycin-C-resistant human Tenon's fibroblast cell line to induced cell death. An antagonistic anti-Fas antibody (ZB4) completely blocked induced cell death. Broad caspase inhibitors specific for caspases-8 and -3 reduced induced deaths in interferon pretreated mitomycin-C-resistant human Tenon's fibroblast cell line in a dose-dependent manner. Interferon-alpha and interferon-gamma render mitomycin-C-resistant human Tenon's fibroblast cell line sensitive to Fas-mediated apoptosis. The mechanism involves increased death-inducing signalling complex formation by upregulation of Fas, Fas-associated protein with death domain and caspase-8 expression. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Agricultural Sales and Services. A Curriculum Guide. Preliminary Draft.

ERIC Educational Resources Information Center

South Carolina State Dept. of Education, Columbia. Agricultural Education Section.

This guide outlines what should be taught to provide training for high school students in agricultural sales and services, and to some degree how and with what resources. The general framework of this 1-year course outline is presented as a problemsolving approach wherein objectives spell out the expected outcomes. After an introductory section on…

FAP-1-mediated activation of NF-kappaB induces resistance of head and neck cancer to Fas-induced apoptosis.

PubMed

Wieckowski, Eva; Atarashi, Yoshinari; Stanson, Joanna; Sato, Taka-Aki; Whiteside, Theresa L

2007-01-01

Molecular mechanisms responsible for tumor resistance to apoptosis often involve the Fas/FasL pathway. While squamous cell carcinomas of the head and neck (SCCHN) express both Fas and FasL, their resistance to self-induced apoptosis or apoptosis mediated by Fas agonistic antibody (CH-11Ab) was independent of the level of Fas surface expression or the presence of soluble Fas in supernatants of primary or metastatic SCCHN cell lines. By in vitro immunoselection, using PCI-15A cell line treated with successive cycles of CH-11 Ab, Fas-resistant sublines with the parental genotype were selected. Such sublines failed to cleave caspase-8 upon Fas engagement and were resistant to CH-11 Ab, although they remained sensitive to VP-16 or staurosporin. In the presence of cycloheximide, the selected SCCHN sublines become susceptible to CH-11 Ab, and showed cleavage of caspase-8, suggesting that apoptosis resistance was mediated by an inhibitory protein(s) acting upstream of caspase-8. Overexpression of Fas-associated phosphatase 1 (FAP-1), but not cellular FLICE-inhibitory protein (cFLIP) in SCCHN sublines was documented by Western blots and RT-PCR analyses. The FAP-1+ selected sublines also downregulated cell surface Fas. A high phosphorylation level of IkappaB kappa, NFkappaB activation and upregulation of Bcl-2 expression were observed in the FAP-1+ sublines. Treatment with the phosphatase inhibitor, orthovanadate, or silencing of FAP-1 with siRNA abolished their resistance to apoptosis, suggesting that FAP-1 phosphatase activity could be responsible for NF-kappaB activation and resistance of SCCHN cells to Fas-mediated apoptosis. 2006 Wiley-Liss, Inc.

Survival Improvement in Human Retinal Pigment Epithelial Cells via Fas Receptor Targeting by miR-374a.

PubMed

Tasharrofi, Nooshin; Kouhkan, Fatemeh; Soleimani, Masoud; Soheili, Zahra-Sheila; Kabiri, Mahboubeh; Mahmoudi Saber, Mohaddeseh; Dorkoosh, Farid Abedin

2017-12-01

Oxidative conditions of the eye could contribute to retinal cells loss through activating the Fas-L/Fas pathway. This phenomenon is one of the leading causes of some ocular diseases like age-related macular degeneration (AMD). By targeting proteins at their mRNA level, microRNAs (miRNAs) can regulate gene expression and cell function. The aim of the present study is to investigate Fas targeting by miR-374a and find whether it can inhibit Fas-mediated apoptosis in primary human retinal pigment epithelial (RPE) cells under oxidative stress. So, the primary human RPE cells were transfected with pre-miR-374a pLEX construct using polymeric carrier and were exposed to H 2 O 2 (200 μM) as an oxidant agent for induction of Fas expression. Fas expression at mRNA and protein level was evaluated by quantitative real-time PCR and Western blot analysis, respectively. These results revealed that miR-374a could prevent Fas upregulation under oxidative conditions. Moreover, Luciferase activity assay confirmed that Fas could be a direct target of miR-374a. The cell viability studies demonstrated that caspase-3 activity was negligible in miR-374a treated cells compared to the controls. Our data suggest miR-374a is a negative regulator of Fas death receptor which is able to enhance the cell survival and protect RPE cells against oxidative conditions. J. Cell. Biochem. 118: 4854-4861, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Preferred Methods for Delivery of Technological Information by the North Carolina Agricultural Extension Service: Opinions of Agricultural Producers Who Use Extension Information.

ERIC Educational Resources Information Center

Richardson, John G.; Mustian, R. David

The findings of a questionnaire survey of 702 North Carolina agricultural producers indicated that communication methods historically used by the North Carolina Agricultural Extension Service for information dissemination are accepted by state farmers and continue to be popular. Information delivery methods most frequently preferred are…

Arthropod genomics research in the United States Department of Agriculture-Agricultural Research Service: Applications of RNA interference and CRISPR gene editing technologies in pest control

USDA-ARS?s Scientific Manuscript database

The Agricultural Research Service (ARS) is the intramural research agency of the United States Department of Agriculture (USDA) which addresses basic scientific questions and develops applied solutions to a range of agricultural problems, and in doing so protects national food security and supports ...

Expression of fas protein on CD4+T cells irradiated by low level He-Ne

NASA Astrophysics Data System (ADS)

Nie, Fan; Zhu, Jing; Zhang, Hui-Guo

2005-07-01

Objective: To investigate the influence on the Expression of Fas protein on CD4+ T cells irradiated by low level He-Ne laser in the cases of psoriasis. Methods:the expression of CD4+ T Fas protein was determined in the casee of psoriasis(n=5) pre and post-low level laser irradiation(30 min、60min and 120min)by flow cytometry as compared withthe control(n=5). Results:In the cases of psoriasis,the expression of CD4+T FAS protein 21.4+/-3.1% was increased significantly than that of control group 16.8+/-2.1% pre-irradiation, p<0.05in the control,there is no difference between pre and post- irradiation,p>0.05in the cases , the expression of CD4+T Fas protein wae positively corelated to the irradiation times, when the energy density arrived to 22.92J/cm2（60 minutes）and 45.84J/cm2（120minutes）, the expression of CD4+ T Fas protein was increased significantly as compared with pre-irradiation,p<0.05.Conclusion: The expression of CD4+T Fas protein may be increased by low level He-Ne laser irradiation ,the uncontrolled status of apoptosis could be corrected.

Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis

PubMed Central

Mou, Haiwei; Moore, Jill; Malonia, Sunil K.; Li, Yingxiang; Ozata, Deniz M.; Hough, Soren; Song, Chun-Qing; Smith, Jordan L.; Fischer, Andrew; Weng, Zhiping; Xue, Wen

2017-01-01

Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras. Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras-expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles’ heel in tumors initiated by oncogenic Kras. PMID:28320962

Induction of Fas-Mediated Apoptosis by Interferon-γ is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary.

PubMed

Lee, Hye-Jeong; Kim, Ji Young; Park, Ji Eun; Yoon, Yong-Dal; Tsang, Benjamin K; Kim, Jong-Min

2016-12-01

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-γ) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-γ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-γ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-γ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-γ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro , very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-γ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo . These findings suggested that IFN-γ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent

Induction of Fas-Mediated Apoptosis by Interferon-γ is Dependent on Granulosa Cell Differentiation and Follicular Maturation in the Rat Ovary

PubMed Central

Lee, Hye-Jeong; Kim, Ji Young; Park, Ji Eun; Yoon, Yong-Dal; Tsang, Benjamin K.; Kim, Jong-Min

2016-01-01

ABSTRACT Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-γ) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-γ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-γ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-γ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-γ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (≥ 1,000 U/mL) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-γ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-γ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent

Discussing Wetlands, Agriculture, and Ecosystem Services: Perspectives from Two Countries

USDA-ARS?s Scientific Manuscript database

A Symposia titled "Wetland Ecosystem Services in Agricultural Landscapes – Comparing Approaches in USA and New Zealand." was held at this year's SWS Annual Conference in Madison. The symposium reviewed the science of wetlands and the role wetlands can play in ensuring the environmental sustainabilit...

Dairy and functional foods research in the Agricultural Research Service

USDA-ARS?s Scientific Manuscript database

The Dairy and Functional Foods Research Unit is the only group in the Agricultural Research Service that is dedicated to solving critical problems in milk utilization and fruit and vegetable byproducts from specialty crops. The many areas of investigation include development of specialty cheese, c...

Site-specific chemical conjugation of human Fas ligand extracellular domain using trans-cyclooctene - methyltetrazine reactions.

PubMed

Muraki, Michiro; Hirota, Kiyonori

2017-07-03

Fas ligand plays a key role in the human immune system as a major cell death inducing protein. The extracellular domain of human Fas ligand (hFasLECD) triggers apoptosis of malignant cells, and therefore is expected to have substantial potentials in medical biotechnology. However, the current application of this protein to clinical medicine is hampered by a shortage of the benefits relative to the drawbacks including the side-effects in systemic administration. Effective procedures for the engineering of the protein by attaching useful additional functions are required to overcome the problem. A procedure for the site-specific chemical conjugation of hFasLECD with a fluorochrome and functional proteins was devised using an inverse-electron-demand Diels-Alder reaction between trans-cyclooctene group and methyltetrazine group. The conjugations in the present study were attained by using much less molar excess amounts of the compounds to be attached as compared with the conventional chemical modification reactions using maleimide derivatives in the previous study. The isolated conjugates of hFasLECD with sulfo-Cy3, avidin and rabbit IgG Fab' domain presented the functional and the structural integrities of the attached molecules without impairing the specific binding activity toward human Fas receptor extracellular domain. The present study provided a new fundamental strategy for the production of the engineered hFasLECDs with additional beneficial functions, which will lead to the developments of the improved diagnostic systems and the effective treatment methods of serious diseases by using this protein as a component of novel molecular tools.

Fas- and Mitochondria-Mediated Signaling Pathway Involved in Osteoblast Apoptosis Induced by AlCl3.

PubMed

Xu, Feibo; Ren, Limin; Song, Miao; Shao, Bing; Han, Yanfei; Cao, Zheng; Li, Yanfei

2018-07-01

Aluminum (Al) is known to induce apoptosis of osteoblasts (OBs). However, the mechanism is not yet established. To investigate the apoptotic mechanism of OBs induced by aluminum trichloride (AlCl 3 ), the primary OBs from the craniums of fetal Wistar rats were exposed to 0 mg/mL (control group, CG), 0.06 mg/mL (low-dose group, LG), 0.12 mg/mL (mid-dose group, MG), and 0.24 mg/mL (high-dose group, HG) AlCl 3 for 24 h, respectively. We observed that AlCl 3 induced OB apoptosis with the appearance of apoptotic morphology and increase of apoptosis rate. Additionally, AlCl 3 treatment activated mitochondrial-mediated signaling pathway, accompanied by mitochondrial membrane potential (ΔΨm) depolarization, release of cytochrome c from the mitochondria to the cytoplasm, as well as survival signal-related factor caspase-9 and caspase-3 activation. AlCl 3 exposure also activated Fas/Fas ligand signaling pathway, presented as Fas, Fas ligand, and Fas-associated death domain expression enhancement and caspase-8 activation, as well as the hydrolysis of Bid to truncated Bid, suggesting that the Fas-mediated signaling pathway might aggravate mitochondria-mediated OB apoptosis through hydrolyzing Bid. Furthermore, AlCl 3 exposure inhibited Bcl-2 protein expression and increased the expressions of Bax, Bak, and Bim in varying degrees. These results indicated that AlCl 3 exposure induced OB apoptosis through activating Fas- and mitochondria-mediated signaling pathway and disrupted B-cell lymphoma-2 family proteins.

No Free Lunch - Trading Away Ecosystem Services from Agriculture in the Brazilian Amazon

NASA Astrophysics Data System (ADS)

Zaks, D.; Foley, J.

2008-12-01

In the age of globalization, many crops and animal products are transported across the long distances for consumption elsewhere. The alteration of water, soil and climate systems from agricultural practices can be attributed to both exporting and importing countries. Quantities of water, carbon and nutrients (e.g. nitrogen and phosphorus) can be tracked throughout the production process and be aggregated from field to table. The synthesis of this data can be used to inform markets to appropriately price the most ecologically efficient production.While agricultural land is undergoing changes around the world, the Brazilian Amazon has seen a dramatic conversion of forest and grassland due to the expanding agricultural frontier, and intense growth in the future has been predicted in the region. As a proof of concept, I plan to study the flow of ecosystem services from the Amazon rainforest basin to the world market. Cattle and soybeans are the two main agricultural products of the region and are produced for both internal consumption and for export. This work quantifies agricultural production and its associated ecosystem services using socio-economic and commodity trade data, numerical ecosystem models and remote sensing products.

Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL.

PubMed

Kojima, H; Eshima, K; Takayama, H; Sitkovsky, M V

1997-09-15

Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.

TRACTOR TUNE-UP AND MAINTENANCE. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 13.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Center for Vocational and Technical Education.

ONE OF A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT UNDERSTANDING OF A SYSTEMATIC PROCEDURE AND ABILITY TO PERFORM TUNEUPS AND MAINTENANCE TASKS. IT WAS DEVELOPED BY A…

A Global Geospatial Ecosystem Services Estimate of Urban Agriculture

NASA Astrophysics Data System (ADS)

Clinton, Nicholas; Stuhlmacher, Michelle; Miles, Albie; Uludere Aragon, Nazli; Wagner, Melissa; Georgescu, Matei; Herwig, Chris; Gong, Peng

2018-01-01

Though urban agriculture (UA), defined here as growing of crops in cities, is increasing in popularity and importance globally, little is known about the aggregate benefits of such natural capital in built-up areas. Here, we introduce a quantitative framework to assess global aggregate ecosystem services from existing vegetation in cities and an intensive UA adoption scenario based on data-driven estimates of urban morphology and vacant land. We analyzed global population, urban, meteorological, terrain, and Food and Agriculture Organization (FAO) datasets in Google Earth Engine to derive global scale estimates, aggregated by country, of services provided by UA. We estimate the value of four ecosystem services provided by existing vegetation in urban areas to be on the order of 33 billion annually. We project potential annual food production of 100-180 million tonnes, energy savings ranging from 14 to 15 billion kilowatt hours, nitrogen sequestration between 100,000 and 170,000 tonnes, and avoided storm water runoff between 45 and 57 billion cubic meters annually. In addition, we estimate that food production, nitrogen fixation, energy savings, pollination, climate regulation, soil formation and biological control of pests could be worth as much as 80-160 billion annually in a scenario of intense UA implementation. Our results demonstrate significant country-to-country variability in UA-derived ecosystem services and reduction of food insecurity. These estimates represent the first effort to consistently quantify these incentives globally, and highlight the relative spatial importance of built environments to act as change agents that alleviate mounting concerns associated with global environmental change and unsustainable development.

Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model.

PubMed

Shi, Zhimin; Li, Yan; Liu, Zhihai; Mi, Jun; Wang, Renxiao

2012-12-01

Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Agricultural Policies Exacerbate Honeybee Pollination Service Supply-Demand Mismatches Across Europe

PubMed Central

Breeze, Tom D.; Vaissière, Bernard E.; Bommarco, Riccardo; Petanidou, Theodora; Seraphides, Nicos; Kozák, Lajos; Scheper, Jeroen; Biesmeijer, Jacobus C.; Kleijn, David; Gyldenkærne, Steen; Moretti, Marco; Holzschuh, Andrea; Steffan-Dewenter, Ingolf; Stout, Jane C.; Pärtel, Meelis; Zobel, Martin; Potts, Simon G.

2014-01-01

Declines in insect pollinators across Europe have raised concerns about the supply of pollination services to agriculture. Simultaneously, EU agricultural and biofuel policies have encouraged substantial growth in the cultivated area of insect pollinated crops across the continent. Using data from 41 European countries, this study demonstrates that the recommended number of honeybees required to provide crop pollination across Europe has risen 4.9 times as fast as honeybee stocks between 2005 and 2010. Consequently, honeybee stocks were insufficient to supply >90% of demands in 22 countries studied. These findings raise concerns about the capacity of many countries to cope with major losses of wild pollinators and highlight numerous critical gaps in current understanding of pollination service supplies and demands, pointing to a pressing need for further research into this issue. PMID:24421873

Inflammation, Apoptosis, and Necrosis Induced by Neoadjuvant Fas Ligand Gene Therapy Improves Survival of Dogs With Spontaneous Bone Cancer

PubMed Central

Modiano, Jaime F; Bellgrau, Donald; Cutter, Gary R; Lana, Susan E; Ehrhart, Nicole P; Ehrhart, EJ; Wilke, Vicki L; Charles, J Brad; Munson, Sibyl; Scott, Milcah C; Pozniak, John; Carlson, Cathy S; Schaack, Jerome; Duke, Richard C

2012-01-01

Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas. PMID:22850679

Functional Polymorphisms of FAS and FASL Gene and Risk of Breast Cancer – Pilot Study of 134 Cases

PubMed Central

Fazaeli, Aliakbar; Eskandari-Nasab, Ebrahim; Arbabi, Farshid; Mashhadi, Mohammad Ali; Taheri, Mohsen; Chaabane, Wiem; Jain, Mayur V.; Łos, Marek J.

2013-01-01

Fas/Fas ligand (FasL) system is one of the key apoptotic signaling entities in the extrinsic apoptotic pathway. De-regulation of this pathway, i.e. by mutations may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between −1377 G/A (rs2234767) and −670 A/G (rs1800682) polymorphisms in Fas as well as single nucleotide polymorphisms INV2nt −124 A/G (rs5030772) and −844 C/T (rs763110) in FasL in a sample of Iranian patients with breast cancer. This case-control study was done on 134 breast cancer patients and 152 normal women. Genomic DNA was extracted from whole blood samples. The polymorphisms were determined by using tetra-ARMS-PCR method. There was no significant difference in the genotype distribution of FAS rs2234767 polymorphism between cases and controls. FAS rs1800682, FASL rs5030772, and FASL rs763110 genotypes showed significant associations with an increasing risk of breast cancer (odds ratio OR = 3.18, P = 0.019; OR = 5.08, P = 0.012; OR = 2.40, P = 0.024, respectively). In conclusion, FAS rs2234767 was not associated with breast cancer risk. Though, FAS rs1800682, FASL rs5030772, and FASL rs763110 polymorphisms were associated with the risk of breast cancer in the examined population. PMID:23326385

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

PubMed

Zhang, X; Miao, X; Sun, T; Tan, W; Qu, S; Xiong, P; Zhou, Y; Lin, D

2005-06-01

The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. To examine the contribution of these polymorphisms to risk of developing lung cancer. Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes

PubMed Central

Backman, Ludvig J; Danielson, Patrik

2013-01-01

Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated in cases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt, which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fas treatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanisms SP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e. induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trend was seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas induces cleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, induced through the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this anti-apoptotic effect of SP is mediated through NK-1 R and Akt-specific pathways. PMID:23577779

Herbicide resistance work in the United States Department of Agriculture-Agricultural Research Service.

PubMed

Vaughn, Kevin C

2003-01-01

Herbicide-resistant weed biotypes are an increasing problem in agriculture, with reports of resistance to almost every herbicide class at some place in the world, and the total number of resistant biotypes at over 250. Agricultural Research Service (ARS) scientists have been key players in this area since the first substantiated occurrence of these resistant biotypes in the 1970s. The most significant of their contributions is the complete unraveling of the mechanism of triazine resistance by Arntzen and colleagues, then with ARS at the University of Illinois. These studies established a high benchmark for research in this area and are a model for all studies in this area. Other ARS scientists have investigated a large number of weed biotypes with resistance to a wide range of herbicide classes and mechanisms of resistance. Collectively, these studies have been used to generate herbicide resistance-management schemes for growers, based upon the herbicide site and the potential for resistance development.

Efficacy of Indexing and Abstracting Services for the Dissemination of Agricultural Information Resources in the Institure for Agricultural Research Library, Ahmadu Bello University, Zaria

NASA Astrophysics Data System (ADS)

Gabriel, KASA, M.

2012-10-01

The efficacy of Indexing and Abstracting service for effective organization, storage and retrieval of information resources for agricultural research in Ahmadu Bello University, Zaria necessitated examining the situation in Agricultural Library, Institute for Agricultural Research, Samaru. The study examines the processes, awareness and problems militating against the effective exploitation of the indexing and abstracting services in the Agricultural library established in 1975. The study was conducted ex post facto, data collected span from 2006 ñ 2010. Total sample sizes of 752 patrons and 20,236 intellectually indexed and abstracted resources were involved in the study. Data collected were subjected to descriptive and inferential statistics. The result revealed that a total of 644 articles were indexed and abstracted, 35% of these was done in 2010. Results for awareness show 452 (60.11%) to be aware in 2008. A total 584 articles were indexed and abstracted from which 167 (28.59%) was retrieved in 2006. Patrons, 270 (35.90%) attributed the poor use of the service to assumption it is a referral unit. The hypothesis testing revealed that there is significant association between articles indexed and abstracted with information consulted by patrons (?2cal,100.31>?2tab,9.488) at 5% level of probability and df, 4. In conclusion, enormous documents on Nigerian agriculture are indexed and abstracted in the unit, implying that the service is desirous and consistent. The study recommends that the unit should explore the use of modern technology, employ a permanent subject specialist, train and retrain the unit staff as well as intensify it general orientation campaigns to focus on awareness and use of the indexing and abstracting services.

78 FR 34128 - Notice of Inventory Completion: U.S. Department of Agriculture, U.S. Forest Service, San Juan...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-WASO-NAGPRA-13012; PPWOCRADN0-PCU00RP14.R50000] Notice of Inventory Completion: U.S. Department of Agriculture, U.S. Forest Service, San Juan.... Department of Agriculture (USDA), Forest Service, San Juan National Forest has completed an inventory of...

Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95).

PubMed

Chen, Qiwei; Pandi, Sudha Priya Soundara; Kerrigan, Lauren; McElvaney, Noel G; Greene, Catherine M; Elborn, J Stuart; Taggart, Clifford C; Weldon, Sinéad

2018-02-24

Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells. Apoptosis and associated caspase activity were analysed in non-CF and CF tracheal and bronchial epithelial cell lines. Basal levels of apoptosis and activity of caspase-3 and caspase-8 were significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings from CF patients compared to non-CF controls. Neutralisation of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. In addition, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway, which may be associated with dysfunctional CFTR. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

Agricultural Products Sales and Service Worker. Ohio's Competency Analysis Profile.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives in Ohio, this document is a comprehensive and verified employer competency profile for agricultural products sales and service occupations. The list contains units (with and without subunits), competencies,…

A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes.

PubMed

Liu, Wei; Jing, Zhen-Tang; Wu, Shu-Xiang; He, Yun; Lin, Yan-Ting; Chen, Wan-Nan; Lin, Xin-Jian; Lin, Xu

2018-05-01

Acute liver failure is a serious clinical problem of which the underlying pathogenesis remains unclear and for which effective therapies are lacking. The Fas receptor/ligand system, which is negatively regulated by AKT, is known to play a prominent role in hepatocytic cell death. We hypothesized that AKT activation may represent a strategy to alleviate Fas-induced fulminant liver failure. We report here that a novel AKT activator, SC79, protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2. Under Fas-signaling stimulation, SC79 inhibited Fas aggregation, prevented the recruitment of the adaptor molecule Fas-associated death domain (FADD) and procaspase-8 [or FADD-like IL-1β-converting enzyme (FLICE)] into the death-inducing signaling complex (DISC), but SC79 enhanced the recruitment of the long and short isoforms of cellular FLICE-inhibitory protein at the DISC. All of the SC79-induced hepatoprotective and DISC-interruptive effects were confirmed to have been reversed by the Akt inhibitor LY294002. These results strongly indicate that SC79 protects hepatocytes from Fas-induced fatal hepatic apoptosis. The potent alleviation of Fas-mediated hepatotoxicity by the relatively safe drug SC79 highlights the potential of our findings for immediate hepatoprotective translation. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

75 FR 23667 - Trade Adjustment Assistance for Farmers