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1

Inhibitory effect of beta-thujaplicin on ultraviolet B-induced apoptosis in mouse keratinocytes.  

PubMed

Sunburn cells are thought to represent ultraviolet B-induced apoptotic keratinocytes. It has been demonstrated that enzymatic and nonenzymatic antioxidants effectively suppress sunburn cell formation, indicating that reactive oxygen species may play a role in the progression of ultraviolet B-induced apoptosis. Metallothionein, a cytosol protein, has antioxidant activity, and overexpression of metallothionein has been reported to reduce the number of sunburn cells in mouse skin. We have also demonstrated that overexpression of metallothionein inhibits ultraviolet B-induced DNA ladder formation in mouse keratinocytes. These findings support the hypothesis that cellular metallothionein may play an important role in the inhibition of ultraviolet B-induced apoptosis in keratinocytes through its antioxidant activity. In the present study, we investigated the effects of beta-thujaplicin, an extract from the woods of Thuja plicata D. Don. and Chamaecyparis obtuse, Sieb. et Zucc., on ultraviolet B-induced apoptosis in keratinocytes and on metallothionein induction. Topical application of beta-thujaplicin decreased the number of ultraviolet B-mediated sunburn cells and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling-positive cells in mouse ear skin. Incubation with beta-thujaplicin suppressed ultraviolet B-induced DNA ladder formation in cultured mouse keratinocytes. Histochemical analysis showed that topical application of beta-thujaplicin induced metallothionein protein in mouse skin. Northern analysis and western blotting revealed significant induction of metallothionein mRNA and metallothionein protein, respectively, in beta-thujaplicin-treated cultured mouse keratinocytes. These findings indicate that beta-thujaplicin inhibits ultraviolet B-induced apoptosis in keratinocytes and strongly suggest that the inhibitory mechanism is due to the antioxidant activity of metallothionein induced by the agent. PMID:9424082

Baba, T; Nakano, H; Tamai, K; Sawamura, D; Hanada, K; Hashimoto, I; Arima, Y

1998-01-01

2

Granzyme B-induced mitochondrial ROS are required for apoptosis.  

PubMed

Caspases and the cytotoxic lymphocyte protease granzyme B (GB) induce reactive oxygen species (ROS) formation, loss of transmembrane potential and mitochondrial outer membrane permeabilization (MOMP). Whether ROS are required for GB-mediated apoptosis and how GB induces ROS is unclear. Here, we found that GB induces cell death in an ROS-dependent manner, independently of caspases and MOMP. GB triggers ROS increase in target cell by directly attacking the mitochondria to cleave NDUFV1, NDUFS1 and NDUFS2 subunits of the NADH: ubiquinone oxidoreductase complex I inside mitochondria. This leads to mitocentric ROS production, loss of complex I and III activity, disorganization of the respiratory chain, impaired mitochondrial respiration and loss of the mitochondrial cristae junctions. Furthermore, we have also found that GB-induced mitocentric ROS are necessary for optimal apoptogenic factor release, rapid DNA fragmentation and lysosomal rupture. Interestingly, scavenging the ROS delays and reduces many of the features of GB-induced death. Consequently, GB-induced ROS significantly promote apoptosis. PMID:25361078

Jacquemin, G; Margiotta, D; Kasahara, A; Bassoy, E Y; Walch, M; Thiery, J; Lieberman, J; Martinvalet, D

2015-04-01

3

LincRNA-p21 acts as a mediator of ING1b-induced apoptosis  

PubMed Central

ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions. PMID:25741593

Tran, U M; Rajarajacholan, U; Soh, J; Kim, T-s; Thalappilly, S; Sensen, C W; Riabowol, K

2015-01-01

4

The Marine Fungal Metabolite, Dicitrinone B, Induces A375 Cell Apoptosis through the ROS-Related Caspase Pathway  

PubMed Central

Dicitrinone B, a rare carbon-bridged citrinin dimer, was isolated from the marine-derived fungus, Penicillium citrinum. It was reported to have antitumor effects on tumor cells previously; however, the details of the mechanism remain unclear. In this study, we found that dicitrinone B inhibited the proliferation of multiple tumor types. Among them, the human malignant melanoma cell, A375, was confirmed to be the most sensitive. Morphologic evaluation, cell cycle arrest and apoptosis rate analysis results showed that dicitrinone B significantly induced A375 cell apoptosis. Subsequent observation of reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) reduction revealed that the apoptosis induced by dicitrinone B may be triggered by over-producing ROS. Further studies indicated that the apoptosis was associated with both intrinsic and extrinsic apoptosis pathways under the regulation of Bcl-2 family proteins. Caspase-9, caspase-8 and caspase-3 were activated during the process, leading to PARP cleavage. The pan-caspase inhibitor, Z-VAD-FMK, could reverse dicitrinone B-induced apoptosis, suggesting that it is a caspase-dependent pathway. Our data for the first time showed that dicitrinone B inhibits the proliferation of tumor cells by inducing cell apoptosis. Moreover, compared with the first-line chemotherapy drug, 5-fluorouracil (5-Fu), dicitrinone B showed much more potent anticancer efficacy, suggesting that it might serve as a potential antitumor agent. PMID:24699111

Chen, Li; Gong, Mei-Wei; Peng, Zhen-Fei; Zhou, Tong; Ying, Min-Gang; Zheng, Qiu-Hong; Liu, Qin-Ying; Zhang, Qi-Qing

2014-01-01

5

Parthenolide sensitizes ultraviolet (UV)-B-induced apoptosis via protein kinase C-dependent pathways.  

PubMed

Parthenolide (PN) is the principal sesquiterpene lactone in feverfew (Tanacetum parthenium) with proven anti-inflammatory properties. We have previously reported that PN possesses strong anticancer activity in ultraviolet B (UVB)-induced skin cancer in SKH-1 hairless mice. In order to further understand the mechanism(s) involved in the anticancer activity of PN, we investigated the role of protein kinase C (PKC) in the sensitization activity of PN on UVB-induced apoptosis. Several subtypes of PKC have been reported to be involved in UVB-induced signaling cascade with both pro- and anti-apoptotic activities. Here we focused on two isoforms of PKC: novel PKCdelta and atypical PKCzeta. In JB6 murine epidermal cells, UVB induces the membrane translocations of both PKCs, and PN pre-treatment enhances the membrane translocation of PKCdelta, but inhibits the translocation of PKCzeta. Similar results were also detected when the activities of these PKCs were tested with the PKC kinase assay. Moreover, pre-treatment with a specific PKCdelta inhibitor, rotterlin, completely diminishes the sensitization effect of PN on UVB-induced apoptosis. When cells were transiently transfected with dominant negative PKCdelta or wild-type PKCzeta, the sensitization effect of PN on UVB-induced apoptosis was also drastically reduced. Further mechanistic study revealed that PKCzeta, but not PKCdelta, is required for UVB-induced p38 MAPK activation and PN is likely to act through PKCzeta to suppress p38 activation in UVB-treated JB6 cells. In conclusion, we demonstrated that PN sensitizes UVB-induced apoptosis via PKC-dependent pathways. PMID:16051639

Won, Yen-Kim; Ong, Choon-Nam; Shen, Han-Ming

2005-12-01

6

Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage.  

PubMed

Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64 ?M. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer. PMID:24140317

Pan, W-R; Chen, P-W; Chen, Y-L S; Hsu, H-C; Lin, C-C; Chen, W-J

2013-12-01

7

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways  

SciTech Connect

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ? We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ? EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ? The effects are involved in caspase-dependent apoptosis and p53 pathway. ? In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ? EriB can be a good candidate for chemotherapy in pancreatic cancer.

Li, Lin [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China) [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Yue, Grace G.L. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Lau, Clara B.S. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Sun, Handong [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China)] [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China); Fung, Kwok Pui [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China) [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Leung, Ping Chung [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Han, Quanbin, E-mail: simonhan@hkbu.edu.hk [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China) [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong (China); Leung, Po Sing, E-mail: psleung@cuhk.edu.hk [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China)

2012-07-01

8

Forskolin protects keratinocytes from ultraviolet (UV) B-induced apoptosis and increases DNA repair independent of its effects on melanogenesis  

PubMed Central

Melanin pigments provide efficient protection against ultraviolet (UV) B radiation but DNA repair also plays a key role in eliminating UV-induced damage and preventing the development of skin cancers. In this study, we demonstrate that forskolin, an agent that increases intracellular levels of cAMP, protects keratinocytes from UVB-induced apoptosis independently from the amount of melanin in the skin. Forskolin enhances the removal of the two major types of UVB-induced DNA damage, cyclobutane pyrimidine dimers and 6,4-photoproducts, by facilitating DNA repair. These findings suggest new preventive approaches with topical formulations of forskolin or other bioactive agents that could be applied to the skin before sun exposure to increase its ability to repair DNA damage. PMID:18580960

Passeron, Thierry; Namiki, Takeshi; Passeron, Hélène; Le Pape, Elodie; Hearing, Vincent J.

2009-01-01

9

Photoprotective effects of two natural products on ultraviolet B-induced oxidative stress and apoptosis in SKH-1 mouse skin.  

PubMed

Solar ultraviolet radiation (UV) is the major cause of nonmelanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. We studied the photoprotective activity of Calluna vulgaris and red grape seed (Vitis vinifera L, Burgund Mare variety [BM]) extracts in vivo in an SKH-1 hairless mice skin model. Fifty 8-week-old female SKH-1 hairless mice were randomly divided into 5 groups (n?=?10 each): controls, UVB-irradiated, C. vulgaris plus UVB-irradiated, BM plus UVB-irradiated, and epigallocatechin gallate (EGCG) plus UVB-irradiated. A dose of 4 mg/mouse per cm² of skin area for both extracts was topically applied to the mice 30 minutes before a single-dose (240 mJ/cm²) UVB exposure. EGCG dissolved in phosphate-buffered saline (pH 6.6; 0.067 M) was administered at 2 mg/mouse per cm². Glutathione peroxidase and catalase activities, reduced glutathione (GSH), malondialdehyde, nitric oxide, and caspase 3 activity were determined in skin homogenates 24 hours after irradiation. A single dose of UVB increased GSH levels and glutathione peroxidase activity in the exposed skin. C. vulgaris and BM pretreatment significantly decreased GSH formation and glutathione peroxidase activity (P?apoptosis. These results suggest that C. vulgaris and BM extracts might be chemopreventive candidates for reducing UV-induced risk for skin cancer. PMID:21470043

Filip, Adriana; Daicoviciu, Doina; Clichici, Simona; Mocan, Teodora; Muresan, Adriana; Postescu, Ion Dan

2011-01-01

10

Fas Antigen Modulates Ultraviolet B-Induced Apoptosis of SVHK Cells: Sequential Activation of Caspases 8, 3, and 1 in the Apoptotic Process  

Microsoft Academic Search

Interferon-? (IFN-?) induces various apoptosis-related proteins, including Fas antigen (Fas) in keratinocytes. Ultraviolet B (UVB) irradiation produces “sunburn cells,” a specific type of apoptosis. Previously, we reported that IFN-? augments Fas-dependent apoptosis of SV40-transformed human keratinocytes (SVHK cells). Caspases are a new class of cysteine proteinases that play an important role in apoptosis. We investigated the mechanism of UVB-induced apoptosis

Hidetoshi Takahashi; Satoshi Nakamura; Kazuhiro Asano; Motoshi Kinouchi; Akemi Ishida-Yamamoto; Hajime Iizuka

1999-01-01

11

SPE 91413SPE 91413 Anangela Garcia  

E-print Network

Modeling System (NEMS) Energy Information Administration #12;SPE Eastern Regional Meeting Gas price (1 Regional Meeting #12;SPE Eastern Regional Meeting #12;SPE Eastern Regional Meeting Annual Energy Outlook (2025) EIA's National Energy Modeling System (NEMS) Annual Energy Outlook (2025) EIA's National Energy

Mohaghegh, Shahab

12

Apoptosis  

NSDL National Science Digital Library

Apoptosis is a highly orchestrated form of cell death in which cells neatly commit suicide by chopping themselves into membrane-packaged bits. Apoptosis, also known as programmed cell death, has caught the imagination of researchers worldwide. This article introduces a special issue on apoptosis.

Linda J. Miller (AAAS; )

1998-08-28

13

Xerophilusin B induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells and does not cause toxicity in nude mice.  

PubMed

Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading cause of cancer-related mortality. Esophageal cancer has a poor prognosis partially due to its low sensitivity to chemotherapy agents, and the development of new therapeutic agents is urgently needed. Here, the antitumor activity of a natural ent-kaurane diterpenoid, xerophilusin B (1), which was isolated from Isodon xerophilus, a perennial herb frequently used in Chinese folk medicine for tumor treatment, was investigated. Compound 1 exhibited antiproliferative effects against esophageal squamous cell carcinoma (ESCC) cell lines in a time- and dose-dependent manner with lower toxicity against normal human and murine cell lines. In vivo studies demonstrated that 1 inhibited tumor growth of a human esophageal tumor xenograft in BALB/c nude mice without significant secondary adverse effects, indicating its safety in treating ESCC. Furthermore, 1 induced G2/M cell cycle arrest and promoted apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway in ESCC cell lines. In conclusion, the observations herein reported showed that 1 is a potential chemotherapeutic agent for ESCC and merits further preclinical and clinical investigation for cancer drug development. PMID:25555195

Yao, Ran; Chen, Zhaoli; Zhou, Chengcheng; Luo, Mei; Shi, Xuejiao; Li, Jiagen; Gao, Yibo; Zhou, Fang; Pu, Jianxin; Sun, Handong; He, Jie

2015-01-23

14

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression.  

PubMed

Novel effective drugs are still urgently needed in the prevention and treatment of oral adenoid cystic carcinoma (ACC). In this study, we have assessed the antitumor potential and molecular mechanisms of flavokawain B (FKB) as a kava chalcone on the ACC-2 cell line in vitro. The results demonstrated that FKB could significantly inhibit the cell proliferation of ACC-2 in a dose-dependent manner that was associated with induced apoptosis and cell cycle G2-M arrest, and the half maximal inhibitory concentration (IC50) of flavokawain-B treatment for 48 h was estimated to be 4.69 ± 0.43 µmol/L. Mechanistically, FKB could induce the release of cytochrome c from mitochondria into the cytosol, and activate the cleavage of caspase-3 and, eventually, the poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner, leading to marked apoptotic effect of ACC-2 cells. The apoptotic action of FKB was associated with the increased expression of proapoptotic proteins: Bim, Bax, Bak and a decreased expression of antiapoptotic Bcl-2. Among them, Bim expression was significantly induced by FKB, and knockdown of Bim expression by short-hairpin RNAs attenuated the inhibitory effect induced by FKB on ACC-2 cells. These results suggest Bim may be one of the potential transcriptional targets, and suggests the potential usefulness of FKB for the prevention and treatment of ACC. PMID:22115332

Zhao, Xi; Chao, Yong-Lie; Wan, Qian-Bing; Chen, Xin-Min; Su, Peng; Sun, Jian; Tang, Yaxiong

2011-12-01

15

Apoptosis  

NSDL National Science Digital Library

This Teaching Resource provides lecture notes and slides for a class covering apoptosis and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture contains a discussion of the apoptosis genes in Caenorhabditis elegans, the properties of the caspases, the major components of the extrinsic apoptotic signal transduction pathway, and the major components of the intrinsic (mitochondrial) apoptotic pathway.

Sherwin Wilk (Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine; )

2005-05-24

16

SPE 83446 Popa, Mohaghegh, Gaskari  

E-print Network

for restimulation. SPE 77597 "Identification of Successful Practices in Hydraulic Fracturing Using Intelligent Data Analysis 3. Production Data Analysis 4. Neural Model Building 5. Successful Practices Analysis #12;SPE that Data can not be trained in its present form! Intelligent system approach was considered

Mohaghegh, Shahab

17

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia  

PubMed Central

p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML. PMID:25387678

Xia, D.Y.; Liu, L.; Hao, M.W.; Liu, Q.; Chen, R.A.; Liang, Y.M.

2014-01-01

18

PEM/SPE fuel cell  

DOEpatents

A PEM/SPE fuel cell including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates.

Grot, Stephen Andreas (Henrietta, NY)

1998-01-01

19

PEM/SPE fuel cell  

DOEpatents

A PEM/SPE fuel cell is described including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates. 4 figs.

Grot, S.A.

1998-01-13

20

Intelligent Time Successive Production Modeling Y. Khazaeni, SPE, S. D. Mohaghegh, SPE, West Virginia University  

E-print Network

SPE 132643 Intelligent Time Successive Production Modeling Y. Khazaeni, SPE, S. D. Mohaghegh, SPE backpropagation algorithm. These networks are then fused together to form the "Intelligent Time-Successive

Mohaghegh, Shahab

21

BIOLOGICAL RESPONSE TO SPE EXPOSURES  

Microsoft Academic Search

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left

J. W. Wilson; F. A. Cucinotta; M. Kim; J. L. Shinn; T. D. Jones; C. K. Chang

1998-01-01

22

Current SPE Hydrodynamic Modeling and Path Forward  

SciTech Connect

Extensive work has been conducted on SPE analysis efforts: Fault effects Non-uniform weathered layer analysis MUNROU: material library incorporation, parallelization, and development of non-locking tets Development of a unique continuum-based-visco-plastic strain-rate-dependent material model With corrected SPE data path is now set for a multipronged approach to fully understand experimental series shot effects.

Knight, Earl E. [Los Alamos National Laboratory; Rougier, Esteban [Los Alamos National Laboratory

2012-08-14

23

Biological Response to SPE Exposures  

NASA Technical Reports Server (NTRS)

It has long been recognized that a single solar particle event (SPE) can produce, over a short period of time, exposures on the order of LD50 for humans under normal physiological conditions. It is further recognized that recovery from injury over the period of exposure would greatly increase the chances of survival (dose rate effects) although such effects were left unquantified. In the present report we use the bioresponse model derived from a broad range of animal and human exposure data for evaluation of troop readiness in tactical nuclear warfare to evaluate the biological risk posed by the solar event of 4 August 1972. The astronaut blood forming organ (BFO) exposure in deep space would have been 2.2 Sv (1.6 Gy) in a space suit, 1.8 Sv (1.3 Gy) in an aluminum pressure vessel, and 0.7 Sv (0.5 Gy) in an equipment room compared to an X-ray mortality threshold of 1.5 Gy (assuming high dose rate). We find BFO dose rate effectiveness factors for this SPE on the order of 3 to 4, greatly reducing the mortality risks for this event. There is an approximate 3 percent chance that an even larger event may occur for which exposures could be 2-4 times higher. Assured survival of the astronaut requires added shelter shielding and a warning system for this event. The required mass of the shelter shield can be greatly reduced by using hydrogenous materials such as polymers, water, food, and other biological materials in its construction. Limitations of the current bioresponse model arise from the exposures taking place in the microgravity environment wherein the immune system is already challenged and the effective mortality threshold may be reduced by a factor of two. Such microgravity effects could greatly affect astronaut risks.

Wilson, J. W.; Cucinotta, F. A.; Kim, M.; Shinn, J. L.; Jones, T. D.; Chang, C. K.

2004-01-01

24

SPE/WPC reserves definitions approved  

SciTech Connect

The SPE Board of Directors recently approved the revised reserves definitions submitted by the SPE Oil and Gas Reserves Committee. The revised definitions, drafted by the Society of Petroleum Engineers/World Petroleum Congresses (WPC) Task Force on Petroleum Reserves Definitions, are the result of several years of collaboration among task force members from both organizations, with input from outside organizations, companies, and individuals. SPE and WPC emphasize that these new definitions are intended to establish standard, general guidelines for petroleum reserves classification that will allow for proper comparison of quantities on a worldwide basis. The definitions, with the exception of portions of the Preamble, are presented here.

NONE

1997-05-01

25

SPE-44 Implements Sperm Cell Fate  

PubMed Central

The sperm/oocyte decision in the hermaphrodite germline of Caenorhabditis elegans provides a powerful model for the characterization of stem cell fate specification and differentiation. The germline sex determination program that governs gamete fate has been well studied, but direct mediators of cell-type-specific transcription are largely unknown. We report the identification of spe-44 as a critical regulator of sperm gene expression. Deletion of spe-44 causes sperm-specific defects in cytokinesis, cell cycle progression, and organelle assembly resulting in sterility. Expression of spe-44 correlates precisely with spermatogenesis and is regulated by the germline sex determination pathway. spe-44 is required for the appropriate expression of several hundred sperm-enriched genes. The SPE-44 protein is restricted to the sperm-producing germline, where it localizes to the autosomes (which contain sperm genes) but is excluded from the transcriptionally silent X chromosome (which does not). The orthologous gene in other Caenorhabditis species is similarly expressed in a sex-biased manner, and the protein likewise exhibits autosome-specific localization in developing sperm, strongly suggestive of an evolutionarily conserved role in sperm gene expression. Our analysis represents the first identification of a transcriptional regulator whose primary function is the control of gamete-type-specific transcription in this system. PMID:22570621

Guevel, Katie; Smith, Harold E.

2012-01-01

26

spe433-01 page 1 INTRODUCTION  

E-print Network

spe433-01 page 1 INTRODUCTION The reality of plate tectonics, as a description of relative motions that plate tectonics has operated in something like its present style for, at most, the past billion years, Driving mechanism and 3-D circulation of plate tectonics, in Sears, J.W., Harms, T.A., and Evenchick, C

Hamilton, Warren B.

27

SPE water electrolyzers in support of the lunar outpost  

NASA Technical Reports Server (NTRS)

During the 1970s, the SPE water electrolyzer, which uses ion exchange membranes as its sole electrolyte, was developed for nuclear submarine metabolic oxygen production. These developments included SPE water electrolyzer operation at up to 3,000 psia and at current densities in excess of 1,000 amps per square foot. The SPE water electrolyzer system is now fully qualified for both the U.S. and U.K. Navies with tens of thousands of system hours accumulated at sea. During the 1980s, the basic SPE water electrolyzer cell structure developed for the Navies was incorporated into several demonstrations for NASA's Space Station Program. Among these were: the SPE regenerative fuel cell for electrical energy storage; the SPE water electrolyzer for metabolic oxygen production; and the high pressure SPE water electrolyzer for reboost propulsion reactant production. In the 1990s, one emphasis will be the development of SPE water electrolyzers for the Lunar Outposts Currently defined potential Lunar Outpost applications for the SPE water electrolyzer include: SPE water electrolyzers for metabolic oxygen and potable water production from reclaimed water; and SPE water electrolyzers operating at high pressure as part of stationary and mobile surface energy storage systems.

Mcelroy, J. F.

1992-01-01

28

SPE dose prediction using locally weighted regression.  

PubMed

When astronauts are outside earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events (SPEs). The total dose received from a major SPE in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be mitigated with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train and provides predictions as accurate as neural network models previously used. PMID:16604634

Hines, J W; Townsend, L W; Nichols, T F

2005-01-01

29

SPE SPE 160638 A Novel Approach to Handle Continuous Wettability Alteration during  

E-print Network

Flooding Process Saad M. Al-Mutairi, Sidqi A. Abu-Khamsin and M. Enamul Hossain, King Fahd University­14 November 2012. This paper was selected for presentation by an SPE program committee following review of information contained in an abstract submitted by the author(s). Contents of the paper have not been reviewed

Hossain, M. Enamul

30

WestVirginiaUniversity SPE 65675 Reservoir Characterization  

E-print Network

information processing _ P_NN_ S_V_D _S _ P_NN_ _ _RN_D #12;WestVirginiaUniversity SPE 65675 METHODOLOGY Tools Saturation · Identification of Water in the formation · Identification of "hard to find" pay zones by identifying high permeability portions of the pay. #12;WestVirginiaUniversity SPE 65675 METHODOLOGY Approach

Mohaghegh, Shahab

31

Enniatin B-induced cell death and inflammatory responses in RAW 267.4 murine macrophages  

SciTech Connect

The mycotoxin enniatin B (EnnB) is predominantly produced by species of the Fusarium genera, and often found in grain. The cytotoxic effect of EnnB has been suggested to be related to its ability to form ionophores in cell membranes. The present study examines the effects of EnnB on cell death, differentiation, proliferation and pro-inflammatory responses in the murine monocyte–macrophage cell line RAW 264.7. Exposure to EnnB for 24 h caused an accumulation of cells in the G0/G1-phase with a corresponding decrease in cyclin D1. This cell cycle-arrest was possibly also linked to the reduced cellular ability to capture and internalize receptors as illustrated by the lipid marker ganglioside GM1. EnnB also increased the number of apoptotic, early apoptotic and necrotic cells, as well as cells with elongated spindle-like morphology. The Neutral Red assay indicated that EnnB induced lysosomal damage; supported by transmission electron microscopy (TEM) showing accumulation of lipids inside the lysosomes forming lamellar structures/myelin bodies. Enhanced levels of activated caspase-1 were observed after EnnB exposure and the caspase-1 specific inhibitor ZYVAD-FMK reduced EnnB-induced apoptosis. Moreover, EnnB increased the release of interleukin-1beta (IL-1?) in cells primed with lipopolysaccharide (LPS), and this response was reduced by both ZYVAD-FMK and the cathepsin B inhibitor CA-074Me. In conclusion, EnnB was found to induce cell cycle arrest, cell death and inflammation. Caspase-1 appeared to be involved in the apoptosis and release of IL-1? and possibly activation of the inflammasome through lysosomal damage and leakage of cathepsin B. -- Highlights: ? The mycotoxin EnnB induced cell cycle arrest, cell death and inflammation. ? The G0/G1-arrest was linked to a reduced ability to internalize receptors. ? EnnB caused lysosomal damage, leakage of cathepsin B and caspase-1 cleavage. ? Caspase-1 was partly involved in both apoptosis and release of IL-1?. ? There was a synergistic action between EnnB and bacterial LPS.

Gammelsrud, A. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway) [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Solhaug, A. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Dendelé, B. [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France)] [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France); Sandberg, W.J. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Ivanova, L. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Kocbach Bølling, A. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Lagadic-Gossmann, D. [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France)] [EA 4427 SeRAIC, IRSET, Université de Rennes 1, IFR 140, Rennes (France); Refsnes, M.; Becher, R. [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)] [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway); Eriksen, G. [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway)] [Norwegian Veterinary Institute, P.O. Box 750, Centrum, N-0106 Oslo (Norway); Holme, J.A., E-mail: jorn.holme@fhi.no [Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo (Norway)

2012-05-15

32

SPE propulsion electrolyzer for NASA's integrated propulsion test article  

NASA Astrophysics Data System (ADS)

Hamilton Standard has delivered a 3000 PSI SPE Propulsion Electrolyzer Stack and Special Test Fixture to the NASA Lyndon B. Johnson Space Center (JSC) Integrated Propulsion Test Article (IPTA) program in June 1990, per contract NAS9-18030. This prototype unit demonstrates the feasibility of SPE-high pressure water electrolysis for future space applications such as Space Station propulsion and Lunar/Mars energy storage. The SPE-Propulsion Electrolyzer has met or exceeded all IPTA program goals. It continues to function as the primary hydrogen and oxygen source for the IPTA test bed at the NASA/JSC Propulsion and Power Division Thermochemical Test Branch.

1991-08-01

33

SPE propulsion electrolyzer for NASA's integrated propulsion test article  

NASA Technical Reports Server (NTRS)

Hamilton Standard has delivered a 3000 PSI SPE Propulsion Electrolyzer Stack and Special Test Fixture to the NASA Lyndon B. Johnson Space Center (JSC) Integrated Propulsion Test Article (IPTA) program in June 1990, per contract NAS9-18030. This prototype unit demonstrates the feasibility of SPE-high pressure water electrolysis for future space applications such as Space Station propulsion and Lunar/Mars energy storage. The SPE-Propulsion Electrolyzer has met or exceeded all IPTA program goals. It continues to function as the primary hydrogen and oxygen source for the IPTA test bed at the NASA/JSC Propulsion and Power Division Thermochemical Test Branch.

1991-01-01

34

Integrin ?v?3 is required for cathepsin B-induced hepatocellular carcinoma progression.  

PubMed

The cysteine protease cathepsin B (Cat B) is important in the progression of tumor cells, however, the function and molecular mechanisms of Cat B in hepatocellular carcinoma (HCC) remain to be elucidated. Our previous study demonstrated that integrin ?v?3 regulated the biological behavior of HCC. The present study demonstrated that Cat B was also important in cell proliferation and apoptosis in HCC. Notably, Cat B was observed to activate the phosphoinositide 3?kinase (PI3K)/Akt signaling pathway to promote HCC proliferation. Furthermore, inhibition of integrin ?v?3 significantly prevented Cat B?induced activation of PI3K/Akt and the progression of HCC. Thus, the results of the present study suggested the presence of a Cat B/integrin ?v?3/PI3K/Akt axis in the regulation of the progression of HCC. PMID:25572981

Xu, Zong-Zhen; Xiu, Peng; Lv, Ju-Wei; Wang, Fu-Hai; Dong, Xiao-Feng; Liu, Feng; Li, Tao; Li, Jie

2015-05-01

35

SPE (tm) regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications  

NASA Technical Reports Server (NTRS)

Viewgraphs on SPE regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications are presented. Topics covered include: hydrogen-oxygen regenerative fuel cell energy storage system; electrochemical cell reactions; SPE cell voltage stability; passive water removal SPE fuel cell; fuel cell performance; SPE water electrolyzers; hydrophobic oxygen phase separator; hydrophilic/electrochemical hydrogen phase separator; and unitized regenerative fuel cell.

Mcelroy, J. F.

1990-01-01

36

Germline survival and apoptosis  

Microsoft Academic Search

Germline apoptosis shares with somatic apoptosis a reliance on key components of the core apoptotic machinery, including CED-3 and CED-4. However, germline apoptosis differs from somatic apoptosis in its regulation. Whereas somatic apoptosis is developmentally programmed by cell lineage, germline apoptosis occurs as part of an oogenesis program. One category of germline apoptosis, dubbed \\

Anton Gartner; Peter R. Boag; T. Keith Blackwell

2008-01-01

37

Intelligent Upscaling of Static and Dynamic Reservoir Properties V.Gholami, SPE and S.D.Mohaghegh, SPE, West Virginia University  

E-print Network

SPE 124477 Intelligent Upscaling of Static and Dynamic Reservoir Properties V.Gholami, SPE and S­7 October 2009. This paper was selected for presentation by an SPE program committee following review. Millions of dollars are invested in logs, core measurements, SCAL studies and geological interpretation

Mohaghegh, Shahab

38

SPE(R)-OBOGS: On-board oxygen generating sustem  

NASA Technical Reports Server (NTRS)

Regulations require oxygen usage by commercial airline flight crews during check out and during certain aircraft configurations. This oxygen is drawn from a high pressure onboard pressure cylinder storage system. In a typical aircraft oxygen cylinder removal for oxygen ground servicing is conducted every 4 to 6 weeks. An on board oxygen generating system has been developed to eliminate the need for oxygen ground servicing. The SPE-OBOGS supplies oxygen during flight in a 'trickle charge' mode to replenish the consumed oxygen at pressures up to 1850 psi. The Electrochemical cell stack is the fundamental SPE-OBOGS system component. The same basic proton exchange membrane technology, previously used for the Gemini program fuel cells and currently used in nuclear submarines as oxygen generators, is used in the SPE-OBOGS. An in-serivce evaluation of the SPE-OBOGS is in the planning stage and a zero gravity version is being promoted for on orbit space suit oxygen system recharge. Summary results of the SPE-OBOGS development will be addressed.

Mcelroy, J.; Smith, W.

1995-01-01

39

Theoretical performance of hydrogen-bromine rechargeable SPE fuel cell  

NASA Technical Reports Server (NTRS)

A mathematical model was formulated to describe the performance of a hydrogen-bromine fuel cell. Porous electrode theory was applied to the carbon felt flow-by electrode and was coupled to theory describing the solid polymer electrolyte (SPE) system. Parametric studies using the numerical solution to this model were performed to determine the effect of kinetic, mass transfer, and design parameters on the performance of the fuel cell. The results indicate that the cell performance is most sensitive to the transport properties of the SPE membrane. The model was also shown to be a useful tool for scale-up studies.

Savinell, Robert F.; Fritts, S. D.

1987-01-01

40

Pacific cod (Gadus macrocephalus Tilesius, 1810) is an important spe-  

E-print Network

153 Pacific cod (Gadus macrocephalus Tilesius, 1810) is an important spe- cies in eastern Bering to track large year classes of cod through time. Historically, scales and otoliths have been the two most these structures have experienced limited success in the case of Pacific cod (Kimura and Lyons, 1990). The Pacific

41

A simple model for solid polymer electrolyte (SPE) water electrolysis  

Microsoft Academic Search

Solid polymer electrolyte (SPE) water electrolysis is analyzed by a simple model based on Butler–Volmer kinetics for electrodes and transport resistance in the polymer electrolyte. An equivalent electrical circuit analogy is provided for the sequential kinetic and transport resistances. The model provides a relation between applied terminal voltage of the electrolysis cell and current density in terms of Nernst potential,

Pyoungho Choi; Dmitri G. Bessarabov; Ravindra Datta

2004-01-01

42

The sandbar shark, Carcharhinus plumbeus, is a large, coastal spe-  

E-print Network

387 The sandbar shark, Carcharhinus plumbeus, is a large, coastal spe- cies of the western north (Bigelow and Schroeder, 1948; Springer, 1960). Sandbar sharks are targeted by commercial fisher- ies and account for up to 60% of the large coastal shark landings in U.S. southern waters (NMFS, 1993). Adults

43

SPE-169507-MS Artificial Intelligence (AI) Assisted History Matching  

E-print Network

SPE-169507-MS Artificial Intelligence (AI) Assisted History Matching Alireza Shahkarami, Shahab D a successful history matching project. The pattern recognition capabilities of Artificial Intelligence and Data the history matching process. SRM is an intelligent prototype of the full-field reservoir simulation model

Mohaghegh, Shahab

44

An improved SPE method for fractionation and identification of phospholipids.  

PubMed

This work reports an efficient and universal SPE method developed for separation and identification of phospholipids derived from complex biological samples. For the separation step, sequential combination of silica gel-aminopropyl-silica gel SPE cartridges is applied. This setup enables separation of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, phosphatidylserine, cardiolipin, and sphingomyelin into four fractions according to the polarity of their headgroups. Sample acquisition of the SPE fractions is performed by a high-resolution LC-MS system consisting of a hybrid linear IT Fourier transform ion cyclotron resonance mass spectrometer coupled to RP-HPLC. The unequivocal advantage of our SPE sample preparation setup is avoidance of analyte peak overlapping in the determination step done by RP-HPLC. Overlapping phospholipid signals would otherwise exert adverse ion suppression effects. An additional benefit of this method is the elimination of polar and nonpolar (e.g. neutral lipids) contaminants from the phospholipid fractions, which highly reduces contamination of the LC-MS system. The method was validated with fermentation samples of organic waste, where 78 distinct phospholipid and sphingomyelin species belonging to six lipid classes were successfully identified. PMID:23349108

Fauland, Alexander; Trötzmüller, Martin; Eberl, Anita; Afiuni-Zadeh, Somaieh; Köfeler, Harald; Guo, Xinghua; Lankmayr, Ernst

2013-02-01

45

Abstract--Evolutionary associations among the four North American spe-  

E-print Network

368 Abstract--Evolutionary associations among the four North American spe- cies of menhadens higher relatedness within the small-scaled and large-scaled menhadens than between these groups. Mitochondrial DNA sequences of the large-scaled menhadens indicated the presence of two ancestral lineages, one

46

SPE (tm) water electrolyzers in support of mission from planet Earth  

NASA Technical Reports Server (NTRS)

During the 1970's, the Solid Polymer Electrolyte (SPE) water electrolyzer, which uses ion exchange membranes as its sole electrolyte, was developed for nuclear submarine metabolic oxygen production. SPE water electrolyzer developments included operation at up to 3,000 psia and at current densities in excess of 1,000 amps per square foot. The SPE water electrolyzer system has accumulated tens of thousands of system hours with the Navies of both the United States and the United Kingdom. During the 1980's, the basic SPE water electrolyzer cell structure developed for the Navies was incorporated into several demonstrators for NASA's Space Station Program. Among these were: (1) the SPE regenerative fuel cell for electrical energy storage; (2) the SPE water electrolyzer for metabolic oxygen production; and (3) the high pressure SPE water electrolyzer for reboost propellant production. In the 1990's, emphasis will be the development of SPE water electrolyzers for Mission from Planet Earth. Currently defined potential applications for the SPE water electrolyzer include: (1) SPE water electrolyzers operating at high pressure as part of a regenerative fuel cell extraterrestrial surface energy storage system; (2) SPE water electrolyzers for propellant production from extraterrestrial indigenous materials; and (3) SPE water electrolyzers for metabolic oxygen and potable water production from reclaimed water.

Mcelroy, J. F.

1991-01-01

47

Lack of mitogenic activity of speG- and speG(dys)-positive Streptococcus dysgalactiae subspecies equisimilis isolates from patients with invasive infections.  

PubMed

In recent years, Streptococcus dysgalactiae subspecies equisimilis has been isolated with an increasing frequency as the cause of invasive streptococcal diseases. For 46 S. dysgalactiae subspecies equisimilis isolates from invasive infections and four isolates from superficial infections, the presence of emm/emmL genes and of genes encoding various different streptococcal superantigens was determined by polymerase chain reaction (PCR). Subsequently, PCR products were identified by DNA sequencing, and the expression of mRNA from superantigen genes was assessed by reverse transcriptase-PCR. The mitogenic activity of S. dysgalactiae subspecies equisimilis was assessed by [3H]thymidine incorporation into human lymphocytes and compared with that of Streptococcus agalactiae and Streptococcus pyogenes. All S. dysgalactiae subspecies equisimilis isolates studied harbored an emm/emmL gene. Only in six of the S. dysgalactiae subspecies equisimilis isolates from invasive infections, speG was detected by PCR, two of which were further identified as speGdys by sequencing of the PCR product. None of the S. dysgalactiae subspecies equisimilis isolates harbored any of the genes speA, speB, speC, speF, speH, speI, speJ, speK, speL, speM, smeZ, or ssa of S. pyogenes. In contrast to S. pyogenes, no expression of speG or speGdys mRNA, respectively, was detected in the reverse transcriptase-PCR assay for any of the speG- or speGdys-positive S. dysgalactiae subspecies equisimilis isolates. Moreover, S. dysgalactiae subspecies equisimilis and S. agalactiae revealed no or very low mitogenic activity, while S. pyogenes was a very powerful inducer of proliferative responses. These findings support the hypothesis that the pathogenicity of S. dysgalactiae subspecies equisimilis may be associated in part with the presence of emm/emmL genes, and suggest that the severity of S. dysgalactiae subspecies equisimilis invasive infections is not mediated by superantigen-induced mitogenicity. PMID:16325550

Brandt, Claudia M; Schweizer, Klaus G; Holland, Regina; Lütticken, Rudolf; Freyaldenhoven, Bettina S

2005-12-01

48

Analysis and Simulations of Near-Field Ground Motion from Source Physics Experiments (spe)  

NASA Astrophysics Data System (ADS)

This work is focused on analysis of near-field measurements (up to 50-70 m from the source) recorded during Source Physics Experiments SPE1, SPE2 and SPE3 in a granitic formation (the Climax Stock) at the Nevada National Security Site (NNSS). The explosive source used in these experiments is a sensitized heavy ANFO (SHANFO) with a well characterized equation of state. The first event, SPE1, had a yield of 0.1 ton, and was detonated at a 55 m depth of burial in a spherical cavity of about 0.3 m radius. SPE2 and SPE3 had an explosive yield of 1 ton, and they were both detonated in the same cavity at a depth of burial of 45 meters. One of the main goals of these experiments was to investigate the possible mechanisms of shear wave generation in the nonlinear source region. Another objective, relating specifically to the SPE2-SPE3 sequence, was to investigate the effect of damage from one explosion on the response of the medium to a second explosion of the same yield and at the same location as the first explosion. Comparison of the results from SPE2 and SPE3 show some interesting trends. . At the shot level, and at deeper locations, the data from SPE3 seem to agree quite well with SPE2 data, indicating that damage from SPE2 had little to no effect on the response of the medium at these locations. On the other hand, SPE3 data consistently show delay in arrival times as well as reduced wave amplitudes both at 50 ft (16 m) depth and at the ground surface, indicating that above the shot horizon damage from SPE2 had a perceptible effect on the SPE3 near field motions. The quality of the near field data at some gages from the SPE1 and SPE2 events is somewhat questionable, with orientation uncertainties making it difficult to ascertain with confidence the extent to which shear wave generation in the source region affected near field motions. New gages were strategically added to the SPE3 test bed to provide the data needed to address this issue and verify previous measurements. The new measurements for SPE 3 show significant tangential motion (up to 30 % of the radial) at many locations as well as azimuthal variations in radial velocities which cannot be predicted by continuum simulations using isotropic plasticity models. Both continuum and discrete 2D/3D simulations are currently being performed to better understand the experimental results, correlate observed motions with heterogeneities in the rock, and aid in assessing the origin of shear waves observed in the seismic frequency band.

Vorobiev, O.; Xu, H.; Lomov, I.; Herbold, E. B.; Glenn, L. A.; Antoun, T.

2012-12-01

49

Pre-shot simulations of far-field ground motion for the Source Physics Experiment (SPE) Explosions at the Climax Stock, Nevada National Security Site: SPE2  

Microsoft Academic Search

The Source Physics Experiment (SPE) is planning a 1000 kg (TNT equivalent) shot (SPE2) at the Nevada National Security Site (NNSS) in a granite borehole at a depth (canister centroid) of 45 meters. This shot follows an earlier shot of 100 kg in the same borehole at a depth 60 m. Surrounding the shotpoint is an extensive array of seismic

R J Mellors; A Rodgers; W Walter; S Ford; H Xu; E Matzel; S Myers; N A Petersson; B Sjogreen; T Hauk; J Wagoner

2011-01-01

50

Predicting Relative-Permeability Curves Directly From Rock Images Dmitriy Silin, SPE, Lawrence Berkeley National Laboratory, and Tad Patzek, SPE, University of Texas, Austin  

E-print Network

SPE 124974 Predicting Relative-Permeability Curves Directly From Rock Images Dmitriy Silin, SPE be either a computer tomography image of a sample of the rock of interest, or a computer- generated image applications. High-resolution rock images and computing power allow direct computation of rock transport

Patzek, Tadeusz W.

51

SPE-NMR metabolite sub-profiling of urine.  

PubMed

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposure. PMID:22932811

Jacobs, Doris M; Spiesser, Laura; Garnier, Maxime; de Roo, Niels; van Dorsten, Ferdi; Hollebrands, Boudewijn; van Velzen, Ewoud; Draijer, Richard; van Duynhoven, John

2012-11-01

52

NEAR FIELD MODELING OF SPE1 EXPERIMENT AND PREDICTION OF THE SECOND SOURCE PHYSICS EXPERIMENTS (SPE2)  

SciTech Connect

Motion along joints and fractures in the rock has been proposed as one of the sources of near-source shear wave generation, and demonstrating the validity of this hypothesis is a focal scientific objective of the source physics experimental campaign in the Climax Stock granitic outcrop. A modeling effort has been undertaken by LLNL to complement the experimental campaign, and over the long term provide a validated computation capability for the nuclear explosion monitoring community. The approach involves performing the near-field nonlinear modeling with hydrodynamic codes (e.g., GEODYN, GEODYN-L), and the far-field seismic propagation with an elastic wave propagation code (e.g., WPP). the codes will be coupled together to provide a comprehensive source-to-sensor modeling capability. The technical approach involves pre-test predictions of each of the SPE experiments using their state of the art modeling capabilities, followed by code improvements to alleviate deficiencies identified in the pre-test predictions. This spiral development cycle wherein simulations are used to guide experimental design and the data from the experiment used to improve the models is the most effective approach to enable a transition from the descriptive phenomenological models in current use to the predictive, hybrid physics models needed for a science-based modeling capability for nuclear explosion monitoring. The objective of this report is to describe initial results of non-linear motion predictions of the first two SPE shots in the Climax Stock: a 220-lb shot at a depth of 180 ft (SPE No.1), and a 2570-lb shot at a depth of 150 ft (SPE No.2). The simulations were performed using the LLNL ensemble granite model, a model developed to match velocity and displacement attenuation from HARDHAT, PILE DRIVER, and SHOAL, as well as Russian and French nuclear test data in granitic rocks. This model represents the state of the art modeling capabilities as they existed when the SPE campaign was launched in 2010, and the simulation results presented here will establish a baseline that will be used for gauging progress as planned modeling improvements are implemented during the remainder of the SPE program. The initial simulations were performed under 2D axisymmetric conditions assuming the geologic medium to be a homogeneous half space. However, logging data obtained from the emplacement hole reveal two major faults that intersect the borehole at two different depth intervals (NSTec report, 2011) and four major joint sets. To evaluate the effect of these discrete structures on the wave forms generated they have performed 2D and 3D analysis with a Lagrangian hydrocode, GEODYN-L that shares the same material models with GEODYN but can explicitly take joints and fault into consideration. They discuss results obtained using these two different approaches in this report.

Antoun, T; Xu, H; Vorobiev, O; Lomov, I

2011-10-20

53

Mathematical modeling of apoptosis  

PubMed Central

Apoptosis is a form of programmed cell death, which is fundamental to all multicellular organisms. Deregulation of apoptosis leads to a number of severe diseases including cancer. Apoptosis is initiated either by extrinsic signals via stimulation of receptors at the cellular surface or intrinsic signals, such as DNA damage or growth factor withdrawal. Apoptosis has been extensively studied using systems biology which substantially contributed to the understanding of this death signaling network. This review gives an overview of mathematical models of apoptosis and the potential of systems biology to contribute to the development of novel therapies for cancer or other apoptosis-related diseases. PMID:23803157

2013-01-01

54

Mathematical modeling of apoptosis.  

PubMed

Apoptosis is a form of programmed cell death, which is fundamental to all multicellular organisms. Deregulation of apoptosis leads to a number of severe diseases including cancer. Apoptosis is initiated either by extrinsic signals via stimulation of receptors at the cellular surface or intrinsic signals, such as DNA damage or growth factor withdrawal. Apoptosis has been extensively studied using systems biology which substantially contributed to the understanding of this death signaling network. This review gives an overview of mathematical models of apoptosis and the potential of systems biology to contribute to the development of novel therapies for cancer or other apoptosis-related diseases. PMID:23803157

Schleich, Kolja; Lavrik, Inna N

2013-01-01

55

SPE1 and SPE2: two essential genes in the biosynthesis of polyamines that modulate +1 ribosomal frameshifting in Saccharomyces cerevisiae.  

PubMed Central

We previously showed that a mutant of Saccharomyces cerevisiae, which cannot make spermidine as a result of a deletion in the SPE2 gene (spe2 delta), exhibits a marked elevation in +1 ribosomal frameshifting efficiency in response to the Ty1 frameshift sequence, CUU AGG C. In the present study, we found that spermidine deprivation alone does not result in increased +1 ribosomal frameshifting efficiency. The high level of +1 ribosomal frameshifting efficiency in spe2 delta cells is the result of the combined effects of both spermidine deprivation and the large increase in the level of intracellular putrescine resulting from the derepression of the gene for ornithine decarboxylase (SPE1) in spermidine-deficient strains. PMID:7961484

Balasundaram, D; Dinman, J D; Tabor, C W; Tabor, H

1994-01-01

56

SOCIAL WORK SPE/AG Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/AG Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ of Social Work or other graduate level courses [Students with no Academic Sub Plan] RQ 2285 Courses Not Used toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE/AG Plan Requirements Campus

Shyy, Wei

57

SOCIAL WORK SPE/MHLTH Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/MHLTH Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ from the School of Social Work or other graduate level courses [Students with no Academic Sub Plan] RQ below has not been used toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE

Shyy, Wei

58

SOCIAL WORK SPE/HLTH Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/HLTH Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ toward specific degree course (Make no exceptions here) #12;SOCIAL WORK SPE/HLTH Plan Requirements Campus Minimum three units from the School of Social Work or other graduate level courses [Academic Sub Plan

Shyy, Wei

59

Solid Polymer Electrolyte (SPE) fuel cell technology, program review, phase 2  

NASA Technical Reports Server (NTRS)

The purpose of the solid polymer electrolyte (SPE) fuel cell program is to advance the SPE fuel cell technology in four target areas. These areas are: (1) reduced fuel cell costs; (2) reduced fuel cell weight; (3) improved fuel cell efficiency; and (4) increased systems compatibility.

1976-01-01

60

The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme  

PubMed Central

The human bacterial pathogen Streptococcus pyogenes has developed a broad variety of virulence mechanisms to evade the actions of the host immune defense. One of the best-characterized factors is the streptococcal cysteine protease SpeB, an important multifunctional protease that contributes to group A streptococcal pathogenesis in vivo. Among many suggested activities, SpeB has been described to degrade various human plasma proteins, including immunoglobulins (Igs). In this study, we show that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB. Since reducing conditions outside eukaryotic cells have to be considered nonphysiological and IgG in a reduced state lacks biological effector functions, we conclude that SpeB does not contribute to S. pyogenes virulence through the proteolytic degradation of Igs. PMID:23569114

Persson, Helena; Vindebro, Reine

2013-01-01

61

Method of making MEA for PEM/SPE fuel cell  

DOEpatents

A method of making a membrane-electrode-assembly (MEA) for a PEM/SPE fuel cell comprising applying a slurry of electrode-forming material directly onto a membrane-electrolyte film. The slurry comprises a liquid vehicle carrying catalyst particles and a binder for the catalyst particles. The membrane-electrolyte is preswollen by contact with the vehicle before the electrode-forming slurry is applied to the membrane-electrolyte. The swollen membrane-electrolyte is constrained against shrinking in the "x" and "y" directions during drying. Following assembly of the fuel cell, the MEA is rehydrated inside the fuel cell such that it swells in the "z" direction for enhanced electrical contact with contiguous electrically conductive components of the fuel cell.

Hulett, Jay S. (West Henrietta, NY)

2000-01-01

62

Apoptosis in heart transplantation.  

PubMed

Apoptosis, or programmed cell death, is a mechanism of cell death that plays a major role during development, homeostasis, and in many disease states. The interaction of the cell membrance protein, Fas, with its ligand, Fas ligand, induces apoptosis in Fas-bearing cells. Several factors induce apoptosis in mammalian cardiomyocytes, including reperfusion injury, hypoxia, mechanical stretch, myocardial infarction, rapid ventricular pacing, and hypertensive heart failure. Although studies in the transplanted hearts of rodents and humans have shown the presence of Fas, Fas ligand, and apoptosis in the myocardium, there is controversy regarding which cells in the myocardium are actually undergoing apoptosis after heart transplantation. It is even less clear what type of relationship, if any, apoptosis has to allograft rejection or post-transplant graft coronary vasculopathy. This review summarizes the current knowledge regarding apoptosis in the transplanted heart and discusses some of the controversies surrounding this new and rapidly expanding area of investigation. PMID:9457443

Shaddy, R E

1997-10-01

63

The Caenorhabditis elegans spe-39 gene is required for intracellular membrane reorganization during spermatogenesis.  

PubMed Central

Caenorhabditis elegans spermatid formation involves asymmetric partitioning of cytoplasm during the second meiotic division. This process is mediated by specialized ER/Golgi-derived fibrous body-membranous organelles (FB-MOs), which have a fibrous body (FB) composed of bundled major sperm protein filaments and a vesicular membranous organelle (MO). spe-39 mutant spermatocytes complete meiosis but do not usually form spermatids. Ultrastructural examination of spe-39 spermatocytes reveals that MOs are absent, while FBs are disorganized and not surrounded by the membrane envelope usually observed in wild type. Instead, spe-39 spermatocytes contain many small vesicles with internal membranes, suggesting they are related to MOs. The spe-39 gene was identified and it encodes a novel hydrophilic protein. Immunofluorescence with a specific SPE-39 antiserum reveals that it is distributed through much of the cytoplasm and not specifically associated with FB-MOs in spermatocytes and spermatids. The spe-39 gene has orthologs in Drosophila melanogaster and humans but no homolog was identified in the yeast genome. This suggests that the specialized membrane biogenesis steps that occur during C. elegans spermatogenesis are part of a conserved process that requires SPE-39 homologs in other metazoan cell types. PMID:14504223

Zhu, Guang-Dan; L'Hernault, Steven W

2003-01-01

64

Salvianolic acid B induces apoptosis in human glioma U87 cells through p38-mediated ROS generation.  

PubMed

Salvianolic acid B (SalB), the main water-soluble bioactive compounds isolated from the traditional Chinese medical herb Danshen, has been shown to exert anti-cancer effect in several cancer cell lines. The aim of our study was to investigate the potential anti-cancer effect of SalB in human glioma U87 cells. We found that treatment with SalB significantly decreased cell viability of U87 cells in a dose- and time-dependent manner. SalB also enhanced the intracellular ROS generation and induced apoptotic cell death in U87 cells. Western blot analysis suggested that SalB increased the phosphorylation of p38 MAPK and p53 in a dose-dependent manner. Moreover, blocking p38 activation by specific inhibitor SB203580 or p38 specific siRNA partly reversed the anti-proliferative and pro-apoptotic effects, and ROS production induced by SalB treatment. The anti-tumor activity of SalB in vivo was also demonstrated in U87 xenograft glioma model. All of these findings extended the anti-cancer effect of SalB in human glioma cell lines, and suggested that these inhibitory effects of SalB on U87 glioma cell growth might be associated with p38 activation mediated ROS generation. Thus, SalB might be concerned as an effective and safe natural anticancer agent for glioma prevention and treatment. PMID:23842993

Wang, Zi-shu; Luo, Peng; Dai, Shu-hui; Liu, Zao-bin; Zheng, Xin-rui; Chen, Tao

2013-10-01

65

IADC/SPE panel probes drilling contracts, business trends  

SciTech Connect

From 1981 to early 1983, more than half the rigs in the U.S. switched from daywork contracts to footage or turnkey drilling. This switch resulted from sudden reversal of the supply/demand picture. It created broad changes in the way operators and drilling contractors do business with each other. It transferred much of the liability and risk to the contractor. It lowered drilling costs. And it caused stunning improvements in rig efficiency. Both operators and contractors are still sorting out the best ways to work under the new order. Their actions on today's challenges will define the future of this marketplace. The form of the contract has been instrumental in changing the nature of drilling. The agreements are changing too. New contracts are more than just a file document mostly for lawyers. They offer a means of communication, a tool for motivation, and a business framework with implications covering business philosophy, profitability, cooperation, and overall results. Four spokesmen from each vantage examined contract trends at the last IADC/SPE Drilling Technology Conference. They hammered out the problems of transition, discussed the long-term future of contracts, and brought forth new proposals beneficial to both parties. Here are the key points from the meeting moderated by Ted Warren, FWA Drilling, and Glen Trimble, Mobil.

Not Available

1983-09-12

66

Potassium Deprivation-Induced Apoptosis of Cerebellar Granule Neurons: A Sequential Requirement for New mRNA and Protein Synthesis, ICE-Like Protease Activity, and Reactive Oxygen Species  

Microsoft Academic Search

Potassium (K1) deprivation-induced apoptosis of cerebellar granule neurons requires new mRNA and protein synthesis. Using a fluorogenic substrate for interleukin-1b converting en- zyme (ICE), we show that K1 deprivation of cerebellar granule neurons induces cycloheximide-sensitive ICE-like protease ac- tivity. A peptide inhibitor of ICE-like protease activity, Ac- YVAD-chloromethylketone (Ac-YVAD-CMK), prevents K1 deprivation-induced apoptosis. Further, reactive oxygen spe- cies (ROS) are

Jorg B. Schulz; Michael Weller; Thomas Klockgether

67

Using Spectral Losses to Map a Damage Zone for the Source Physics Experiments (SPE)  

NASA Astrophysics Data System (ADS)

We performed a series of cross-borehole seismic experiments in support of the Source Physics Experiments (SPE). These surveys, which were conducted in a granitic body using a sparker source and hydrophone string, were designed to image the damage zone from two underground explosions (SPE2 and SPE3). We present results here from a total of six boreholes (the explosive shot emplacement hole and 5 satellite holes, 20-35 meters away) where we found a marked loss of high frequency energy in ray paths traversing the region near the SPE explosions. Specifically, the frequencies above ~400 Hz were lost in a region centered around 45 meters depth, coincident with SPE2 and SPE3 shots. We further quantified these spectral losses, developed a map of where they occur, and evaluated the attenuation effects of raypath length (i.e. source-receiver offset). We attribute this severe attenuation to the inelastic damage (i.e. cracking and pulverizing) caused by the large chemical explosions and propose that frequency attenuation of this magnitude provides yet another tool for detecting the damage due to large underground explosions. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Knox, H. A.; Abbott, R. E.; Bonal, N.; Preston, L. A.

2013-12-01

68

Vps33b pathogenic mutations preferentially affect VIPAS39/SPE-39-positive endosomes  

PubMed Central

Mutations in Vps33 isoforms cause pigment dilution in mice (Vps33a, buff) and Drosophila (car) and the neurogenic arthrogryposis, renal dysfunction and cholestasis syndrome in humans (ARC1, VPS33B). The later disease is also caused by mutations in VIPAS39, (Vps33b interacting protein, apical-basolateral polarity regulator, SPE-39 homolog; ARC2), a protein that interacts with the HOmotypic fusion and Protein Sorting (HOPS) complex, a tether necessary for endosome–lysosome traffic. These syndromes offer insight into fundamental endosome traffic processes unique to metazoans. However, the molecular and cellular mechanisms underlying these mutant phenotypes remain poorly understood. Here we investigate interactions of wild-type and disease-causing mutations in VIPAS39/SPE-39 and Vps33b by yeast two hybrid, immunoprecipitation and quantitative fluorescent microscopy. We find that although few mutations prevent interaction between VIPAS39/SPE-39 and Vps33b, some mutants fragment VIPAS39/SPE-39-positive endosomes, but all mutants alter the subcellular localization of Vps33b to VIPAS39/SPE-39-positive endosomes. Our data suggest that the ARC syndrome may result through impaired VIPAS39/SPE-39 and Vps33b-dependent endosomal maturation or fusion. PMID:23918659

Tornieri, Karine; Zlatic, Stephanie A.; Mullin, Ariana P.; Werner, Erica; Harrison, Robert; L'Hernault, Steven W.; Faundez, Victor

2013-01-01

69

Rapid narrow band elution for on-line SPE using a novel solvent plug injection technique.  

PubMed

Determination of trace constituents in biological and environmental samples usually requires a pre-concentration step. While solid-phase extraction (SPE) has been widely used, it is slow, labor intensive and adversely affected by analytical errors from handling. On-line SPE eliminates some of the flaws but often suffers from solvent compatibility problems with the subsequent chromatography separation. In this study, we are presenting a technical solution for overcoming some of these compatibility issues, by utilizing a fully automated, focused SPE sample transfer technique utilizing narrow-band solvent plugs, for seamless hyphenation with high-performance liquid chromatography (HPLC) or flow injection mass spectrometry (MS). A wide range of pharmaceutical compounds was studied in different sample matrices. Short plugs of high elution strength solvent were generated by means of an electrically actuated sample loop and enrichment and transfer steps monitored using on-line SPE-MS. The impact of the solvent plugs on chromatographic separation was studied using hyphenated SPE-LC-MS. By carefully examining elution profiles of solvent plugs of different compositions, optimum conditions for quantitative elution within well-defined volumes were found for all substances. In addition, the highly focused elution bands resulted in excellent retention time and peak area reproducibilities when injected on-line onto HPLC columns. Finally, to demonstrate proof-of-principle, the fully integrated on-line SPE-LC-MS system was applied to the analysis of spiked urine and river water samples. PMID:22669308

Gode, David; Martin, Markus M; Steiner, Frank; Huber, Christian G; Volmer, Dietrich A

2012-08-01

70

Calpains, mitochondria, and apoptosis  

PubMed Central

Mitochondrial activity is critical for efficient function of the cardiovascular system. In response to cardiovascular injury, mitochondrial dysfunction occurs and can lead to apoptosis and necrosis. Calpains are a 15-member family of Ca2+-activated cysteine proteases localized to the cytosol and mitochondria, and several have been shown to regulate apoptosis and necrosis. For example, in endothelial cells, Ca2+ overload causes mitochondrial calpain 1 cleavage of the Na+/Ca2+ exchanger leading to mitochondrial Ca2+ accumulation. Also, activated calpain 1 cleaves Bid, inducing cytochrome c release and apoptosis. In renal cells, calpains 1 and 2 promote apoptosis and necrosis by cleaving cytoskeletal proteins, which increases plasma membrane permeability and cleavage of caspases. Calpain 10 cleaves electron transport chain proteins, causing decreased mitochondrial respiration and excessive activation, or inhibition of calpain 10 activity induces mitochondrial dysfunction and apoptosis. In cardiomyocytes, calpain 1 activates caspase 3 and poly-ADP ribose polymerase during tumour necrosis factor-?-induced apoptosis, and calpain 1 cleaves apoptosis-inducing factor after Ca2+ overload. Many of these observations have been elucidated with calpain inhibitors, but most calpain inhibitors are not specific for calpains or a specific calpain family member, creating more questions. The following review will discuss how calpains affect mitochondrial function and apoptosis within the cardiovascular system. PMID:22581845

Smith, Matthew A.; Schnellmann, Rick G.

2012-01-01

71

Robust Determination of the Pore Space Morphology in Sedimentary Rocks Dmitry B. Silin, SPE, Lawrence Berkeley National Laboratory; Guodong Jin, SPE, UC Berkeley; and  

E-print Network

SPE 84296 Robust Determination of the Pore Space Morphology in Sedimentary Rocks Dmitry B. Silin the mor- phology (shapes and connectivity) of the pore space of a sedimentary rock. Our approach is based, the proposed algorithm produces a stick-and- ball diagram of the rock pore space. One of distinctive features

Patzek, Tadeusz W.

72

c-Abl mediates endothelial apoptosis induced by inhibition of integrins ?v?3 and ?v?5 and by disruption of actin  

PubMed Central

Inhibition of integrins ?v?3 and ?v?5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss of spreading on vitronectin, cell detachment, and apoptosis. We demonstrate that cell detachment is not required for apoptosis because plating on bovine serum albumin–blocked poly-L-lysine (allows attachment, but not integrin ligation and cell spreading) also induced apoptosis. Latrunculin B (LatB), which inhibits F-actin polymerization, induced transient loss of HBMEC spreading on vitronectin, but not their detachment, and induced apoptosis despite recovery of cell spreading. However, LatB did not cause apoptosis in 5 tumor cell lines. In HBMECs, both LatB and RGDfV induced transient Y412 and Y245 phosphorylation of endogenous c-Abl, a nonreceptor tyrosine kinase that reciprocally regulates F-actin. LatB also induced nuclear translocation of c-Abl in HBMECs. STI-571 (imatinib), a targeted therapy for BCR-ABL1+ leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. LatB-induced HBMEC apoptosis, and its inhibition by STI-571 also occurred in a 3-dimensional collagen model, supporting physiologic relevance. Last, siRNA to c-Abl (but not nonspecific siRNA) also inhibited RGDfV- and LatB-induced apoptosis. Thus, endogenous c-Abl mediates endothelial apoptosis induced by inhibition of integrins ?v?3/?v?5 or by LatB-induced disruption of F-actin. PMID:20124512

Xu, Jingying; Millard, Melissa; Ren, Xiuhai; Cox, Orla T.

2010-01-01

73

An Atypical E3 Ligase Zinc Finger Protein 91 Stabilizes and Activates NF-?B-inducing Kinase via Lys63-linked Ubiquitination*  

PubMed Central

The NF-?B transcription factors control many physiological processes, including inflammation, immunity, and apoptosis. Its activity contributes to the development of various cell malignancies. NF-?B-inducing kinase (NIK) plays a pivotal role in NF-?B activation. However, the molecular mechanism to stabilize and activate NIK remains elusive, although it is known that cIAP1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate NIK for degradation. Here, we report a novel NF-?B-related zinc finger protein 91 (ZFP91) that stabilizes and activates NIK in a ubiquitination-dependent manner. We show that ZFP91 interacts with and promotes the Lys63-linked ubiquitination of NIK and subsequent processing of p100 to p52. The results of in vitro biochemical assays indicate that ZFP91 functions as an E3 ligase directly to NIK. Remarkably, the ubiquitination of NIK coincides with its Thr559 phosphorylation. Furthermore, knockdown of ZFP91 expression by RNA interference inhibits the CD40 ligation-induced activation of NIK and p100 processing as well as the expression of noncanonical NF-?B target genes. These data clearly indicate that ZFP91 is an important regulator of the noncanonical NF-?B pathway. PMID:20682767

Jin, Xuejun; Jin, Hong Ri; Jung, Haeng Sun; Lee, Se Jeong; Lee, Jeong-Hyung; Lee, Jung Joon

2010-01-01

74

Apoptosis in pneumovirus infection.  

PubMed

Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages) during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs. PMID:23344499

van den Berg, Elske; van Woensel, Job B M; Bem, Reinout A

2013-01-01

75

Apoptosis in Pneumovirus Infection  

PubMed Central

Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages) during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs. PMID:23344499

van den Berg, Elske; van Woensel, Job B.M.; Bem, Reinout A.

2013-01-01

76

Apoptosis In Vivo  

Microsoft Academic Search

\\u000a Apoptosis is a complex and highly regulated process with numerous and varied biological consequences, it is typically described\\u000a as a sequence of morphological events that can be easily recognized histologically. In fact, the initial identification and\\u000a subsequent characterization of apoptosis were based on microscopic observations of its occurrence in vivo. In the early 1970’s, an experimental pathologist recognized variations in

L. C. Stephens; L. Milas; K. K. Ang; K. A. Mason; R. E. Meyn

77

PHARMACOLOGIC PROBING OF AMPHOTERICIN B-INDUCED RENAL DYSFUNCTION IN THE NEONATAL RAT  

EPA Science Inventory

Pharmacologic Probing of Amphotericin B-Induced Renal Dysfunction in the Neonatal Rat. Gray, J.A., and Kavlock, R.J. (1988). Toxicol. Appl. Pharmacol. 93, 360-368. Acetazolamide, furosemide, chlorothiazide, and amiloride pharmacologic agents that act primarily in the proximal tub...

78

Understanding the Rate of Clean Up for Oil Zones after a Gel Treatment R.S. Seright, SPE, New Mexico Petroleum Recovery Research Center, W. Brent Lindquist, SPE, and Rong Cai,  

E-print Network

SPE 112976 Understanding the Rate of Clean Up for Oil Zones after a Gel Treatment R.S. Seright, SPE for a production well to "clean up" or restore productivity after a gel treatment. Consequently, we were interested both in water-wet Berea sandstone and in hydrophobic porous polyethylene. In hydrophobic porous

New York at Stoney Brook, State University of

79

Theoretical performance of hydrogen-bromine rechargeable SPE fuel cell. [Solid Polymer Electrolyte  

NASA Technical Reports Server (NTRS)

A mathematical model was formulated to describe the performance of a hydrogen-bromine fuel cell. Porous electrode theory was applied to the carbon felt flow-by electrode and was coupled to theory describing the solid polymer electrolyte (SPE) system. Parametric studies using the numerical solution to this model were performed to determine the effect of kinetic, mass transfer, and design parameters on the performance of the fuel cell. The results indicate that the cell performance is most sensitive to the transport properties of the SPE membrane. The model was also shown to be a useful tool for scale-up studies.

Savinell, R. F.; Fritts, S. D.

1988-01-01

80

Spacecraft Solar Particle Event (SPE) Shielding: Shielding Effectiveness as a Function of SPE model as Determined with the FLUKA Radiation Transport Code  

NASA Technical Reports Server (NTRS)

Analysis of both satellite and surface neutron monitor data demonstrate that the widely utilized Exponential model of solar particle event (SPE) proton kinetic energy spectra can seriously underestimate SPE proton flux, especially at the highest kinetic energies. The more recently developed Band model produces better agreement with neutron monitor data ground level events (GLEs) and is believed to be considerably more accurate at high kinetic energies. Here, we report the results of modeling and simulation studies in which the radiation transport code FLUKA (FLUktuierende KAskade) is used to determine the changes in total ionizing dose (TID) and single-event environments (SEE) behind aluminum, polyethylene, carbon, and titanium shielding masses when the assumed form (i. e., Band or Exponential) of the solar particle event (SPE) kinetic energy spectra is changed. FLUKA simulations have fully three dimensions with an isotropic particle flux incident on a concentric spherical shell shielding mass and detector structure. The effects are reported for both energetic primary protons penetrating the shield mass and secondary particle showers caused by energetic primary protons colliding with shielding mass nuclei. Our results, in agreement with previous studies, show that use of the Exponential form of the event

Koontz, Steve; Atwell, William; Reddell, Brandon; Rojdev, Kristina

2010-01-01

81

Regulation of death receptor expression and TRAIL\\/Apo2L-induced apoptosis by NF-?B  

Microsoft Academic Search

TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-?B induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein I?B? or a transactivation-deficient mutant of c-Rel reduces expression of either

Rajani Ravi; Gauri. C. Bedi; Laura W. Engstrom; Qinwen Zeng; Bijoyesh Mookerjee; Céline Gélinas; Ephraim J. Fuchs; Atul Bedi

2001-01-01

82

Gonadal cell apoptosis.  

PubMed

Apoptosis is an important cellular process by which superfluous or unwanted cells are deleted from an organism during tissue remodeling and differentiation. Recent studies have demonstrated the role of this programmed cell death or "controlled cell suicide" in the physiological function of an organism. Suppression of apoptosis increases the susceptibility of an individual to malignancy whereas uncontrolled cell death is associated with degenerative diseases. Normal development of both female and male gonads is characterized by massive cell death. More than 99% of ovarian follicles endowed at early life are destined to undergo apoptosis and the exhaustion of these follicles serves as a "clock" for female reproductive senescence. In the testis, up to 75% of male germ cells also undergo apoptosis, perhaps as a mechanism to delete superfluous or defective germ cells. Gonadal cell apoptosis provides valuable models to study hormonal regulation of apoptosis. In the ovary, gonadotropins, estrogens, growth hormone, growth factors (IGFI, EGF/TGF-alpha, basic FGF), cytokine (interleukin-1 beta) and nitric oxide act in concert to ensure the survival of preovulatory follicles. In contrast, androgens, interleukin-6 and gonadal GnRH-like peptide are apoptotic factors. Developmental studies further indicate that fractions of endowed follicles are recruited throughout the reproductive life whereas most of the primordial follicles are "arrested" at the initial stage of development for a prolonged time. Because a transcriptional factor WT1 is expressed in high levels in follicles at early stages of development and because WT1 over-expression represses the promoter activity of inhibin-alpha gene, this nuclear protein may be important in the maintenance of follicles at early stages of development. Once a cohort of follicles is recruited to grow, it is destined to undergo apoptosis unless rescued by survival factors. After puberty onset and under gonadotropin stimulation, some of the growing antral follicles are "selected" to continue their final maturation and secrete high levels of estrogens to trigger ovulation. Following repeated cycles of recruitment, atresia or ovulation, the follicle reserve is exhausted, thus signaling the onset of reproductive senescence. Although the somatic granulosa cell is the major cell type undergoing apoptosis in the ovary, the germ cells in the testis also exhibit signs of apoptotic cell demise. In the testis, gonadotropins and androgens act as survival factors whereas exposure to elevated temperature in cryptorchid testes increases apoptosis. In the seasonally breeding hamster model, photoperiod-entrained regression and recrudescence of testis tissue serves as a unique natural model of apoptosis. With recent advances in our understanding of the cellular mechanism of apoptosis, including the elucidation of the Ced9/bc12 and Ced3/ICE family of proteins, further investigation of gonadal apoptosis may lead to a better understanding of gonadal degenerative disorders (such as premature ovarian failure and oligospermia), reproductive senescence and tumorigenesis. The gonadal model should also be valuable in studying the regulation of intracellular apoptosis genes by external hormonal signals. PMID:8701090

Hsueh, A J; Eisenhauer, K; Chun, S Y; Hsu, S Y; Billig, H

1996-01-01

83

Solid phase extraction-liquid chromatography (SPE-LC) interface for automated peptide separation and identification by tandem mass spectrometry  

NASA Astrophysics Data System (ADS)

Reversed-phase solid phase extraction (SPE) is a simple and widely used technique for desalting and concentration of peptide and protein samples prior to mass spectrometry analysis. Often, SPE sample preparation is done manually and the samples eluted, dried and reconstituted into 96-well titer plates for subsequent LC-MS/MS analysis. To reduce the number of sample handling stages and increase throughput, we developed a robotic system to interface off-line SPE to LC-ESI-MS/MS. Samples were manually loaded onto disposable SPE tips that subsequently were connected in-line with a capillary chromatography column. Peptides were recovered from the SPE column and separated on the RP-LC column using isocratic elution conditions and analysed by electrospray tandem mass spectrometry. Peptide mixtures eluted within approximately 5 min, with individual peptide peak resolution of ~7 s (FWHM), making the SPE-LC suited for analysis of medium complex samples (3-12 protein components). For optimum performance, the isocratic flow rate was reduced to 30 nL/min, producing nanoelectrospray like conditions which ensure high ionisation efficiency and sensitivity. Using a modified autosampler for mounting and disposing of the SPE tips, the SPE-LC-MS/MS system could analyse six samples per hour, and up to 192 SPE tips in one batch. The relatively high sample throughput, medium separation power and high sensitivity makes the automated SPE-LC-MS/MS setup attractive for proteomics experiments as demonstrated by the identification of the components of simple protein mixtures and of proteins recovered from 2DE gels.

Hørning, Ole Bjeld; Theodorsen, Søren; Vorm, Ole; Jensen, Ole Nørregaard

2007-12-01

84

Fertilization in C. elegans requires an intact C-terminal RING finger in sperm protein SPE-42  

PubMed Central

Background The C. elegans sperm protein SPE-42, a membrane protein of unknown structure and molecular function, is required for fertilization. Sperm from worms with spe-42 mutations appear normal but are unable to fertilize eggs. Sequence analysis revealed the presence of 8 conserved cysteine residues in the C-terminal cytoplasmic domain of this protein suggesting these residues form a zinc-coordinating RING finger structure. Results We made an in silico structural model of the SPE-42 RING finger domain based on primary sequence analysis and previously reported RING structures. To test the model, we created spe-42 transgenes coding for mutations in each of the 8 cysteine residues predicted to coordinate Zn++ ions in the RING finger motif. Transgenes were crossed into a spe-42 null background and protein function was measured by counting progeny. We found that all 8 cysteines are required for protein function. We also showed that sequence differences between the C-terminal 29 and 30 amino acids in C. elegans and C. briggsae SPE-42 following the RING finger domain are not responsible for the failure of the C. briggsae SPE-42 homolog to rescue C. elegans spe-42 mutants. Conclusions The results suggest that a bona fide RING domain is present at the C-terminus of the SPE-42 protein and that this motif is required for sperm-egg interactions during C. elegans fertilization. Our structural model of the RING domain provides a starting point for further structure-function analysis of this critical region of the protein. The C-terminal domain swap experiment suggests that the incompatibility between the C. elegans and C. briggsae SPE-42 proteins is caused by small amino acid differences outside the C-terminal domain. PMID:21345212

2011-01-01

85

spe436-16 page 1 The Geological Society of America  

E-print Network

spe436-16 page 1 The Geological Society of America Special Paper 436 2007 Sedimentary response Development, Griboedova Street #2, 625000 Tyumen, Russia D. Zinniker Geology and Geophysics, Yale University Zones: Geological Society of America Special Paper 436, p. XXX­XXX, doi: 0

Johnson, Cari

86

The Marine Mammal Protection Act (MMPA) prohibits the take of all marine mammal spe-  

E-print Network

The Marine Mammal Protection Act (MMPA) prohibits the take of all marine mammal spe- cies in U, or kill any marine mammal." HarassmentHarassment is defined in the MMPA as "any act of pursuit, torment, or annoyance which has the potential to injure a marine mammal or marine mammal stock in the wild; or has

87

STANDARD ADDITION METHOD FOR THE DETERMINATION OF1 PHARMACEUTICAL RESIDUES IN DRINKING WATER BY SPE-2  

E-print Network

STANDARD ADDITION METHOD FOR THE DETERMINATION OF1 PHARMACEUTICAL RESIDUES IN DRINKING WATER BY SPE compounds in drinking or waste22 water processes has become very popular in recent years. LC-MS/MS is a powerful23 analytical tool often used to determine pharmaceutical residues at trace level in water.24

Boyer, Edmond

88

SOCIAL WORK SPE/CY Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/CY Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ Minimum nine units from the School of Social Work or other graduate level courses [Students02/1410 (09/03/2002) LN 0030 Minimum three units from the School of Social Work or other graduate

Shyy, Wei

89

SOCIAL WORK SPE/CSS Plan Requirements Campus: UMICH RG = Requirement Group  

E-print Network

SOCIAL WORK SPE/CSS Plan Requirements Campus: UMICH RG = Requirement Group Career: GSW RQ Minimum nine units from the School of Social Work or other graduate level courses [Students Effective FA02/1410 (09/03/2002) LN 0030 Minimum three units from the School of Social Work or other

Shyy, Wei

90

spe451-00 1st pgs page v Introduction: Managing Rivers with Broad Historical Changes  

E-print Network

spe451-00 1st pgs page v v Introduction: Managing Rivers with Broad Historical Changes and Human global environmental change, water resources, river restoration, and sustainable river management of studies and inter- pretations of river-channel change that reflect modern viewpoints of river management

James, L. Allan

91

EC-SPE-stripline-NMR analysis of reactive products: a feasibility study.  

PubMed

Flow-through electrochemical conversion (EC) of drug-like molecules was hyphenated to miniaturized nuclear magnetic resonance spectroscopy (NMR) via on-line solid-phase extraction (SPE). After EC of the prominent p38? mitogen-activated protein kinase inhibitor BIRB796 into its reactive products, the SPE step provided preconcentration of the EC products and solvent exchange for NMR analysis. The acquisition of NMR spectra of the mass-limited samples was achieved in a stripline probe with a detection volume of 150 nL offering superior mass sensitivity. This hyphenated EC-SPE-stripline-NMR setup enabled the detection of the reactive products using only minute amounts of substrate. Furthermore, the integration of conversion and detection into one flow setup counteracts incorrect assessments caused by the degradation of reactive products. However, apparent interferences of the NMR magnetic field with the EC, leading to a low product yield, so far demanded relatively long signal averaging. A critical assessment of what is and what is not (yet) possible with this approach is presented, for example in terms of structure elucidation and the estimation of concentrations. Additionally, promising routes for further improvement of EC-SPE-stripline-NMR are discussed. PMID:23812883

Falck, David; Oosthoek-de Vries, Anna J; Kolkman, Ard; Lingeman, Henk; Honing, Maarten; Wijmenga, Sybren S; Kentgens, Arno P M; Niessen, Wilfried M A

2013-08-01

92

Spaceflight Associated Apoptosis  

NASA Technical Reports Server (NTRS)

Lymphoid tissues have been shown to atrophy in rats flown on Russian spaceflights. Histological examination indicated evidence for cell degradation. Lymphoid tissues from rats flown on Spacelab Life Sciences-2 mission were analyzed for apoptosis by evidence of fragmented lymphocytes, which could be engulfed by macrophages, or DNA strand breaks using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Apoptosis was not detected in the thymus and spleen collected inflight or from the synchronous ground rats but was detected in the thymus, spleen and inguinal lymph node of the flight animals on recovery. These results indicate that the apoptosis observed in the lymphatic tissues of the rats on recovery could have been induced by the gravitational stress of reentry, corroborating the findings from the early space-flight observations.

Ichiki, Albert T.; Gibson, Linda A.; Allebban, Zuhair

1996-01-01

93

Caspase Family Proteases and Apoptosis  

Microsoft Academic Search

Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated in an orderly way by a series of signal cascades under certain circumstances. The caspase-cascade system plays vital roles in the induction, transduction and amplification of intracellular apoptotic signals. Caspases, closely associated with apoptosis,

Ting-Jun FAN; Li-Hui HAN; Ri-Shan CONG; Jin LIANG

2005-01-01

94

Apoptosis: Genetically Programmed Cell Death  

Microsoft Academic Search

Extensively and successfully studied problems of programmed cell death are considered. Recent evidence on apoptosis genes is presented, including the bcl-2 family and other genes with similar functions. A scheme of pathways of the main apoptosis mechanism is constructed. Examples of associations of apoptosis and diseases are presented in a special section.

L. S. Popov; L. I. Korochkin

2004-01-01

95

UV-B-induced plant stress as a possible cause of ten-year hare cycles  

Microsoft Academic Search

Predation has been assumed to be a necessary factor in the ten-year population cycle of the snowshoe hare (Lepus americanus) and Canadian lynx (Lynx canadensis). The UV-B-induced plant stress hypothesis, in contrast, predicts that hare performance, especially reproduction, is negatively related to sunspot numbers, because production of UV-B-protective phenolics in food plants in periods of low sunspot activity, when the

Vidar Selås

2006-01-01

96

Apoptosis in Colorectal Cancer  

PubMed Central

Abstract Apoptosis is an inborn process that has been preserved during evolution; it allows the cells to systematically inactivate, destroy and dispose of their own components thus leading to their death. This programme can be activated by both intra and extracellular mechanisms. The intracellular components involve a genetically defined development programme while the extracellular aspects regard endogenous proteins, cytokines and hormones as well as xenobiotics, radiations, oxidative stress and hypoxia. The ability of a cell to enter apoptosis as a response to a “death" signal depends on its proliferative status, the position in the cell cycle and also on the controlled expression of those genes that have the capacity of promoting and inhibiting cell death. The fine regulation of these parameters needs to be maintained in order to ensure the physiological environment required for the induction of apoptosis. Any malfunction in any of the steps of controlled cellular death can lead to dysfunctions and, as a consequence, to different pathological conditions. The importance of apoptosis lies in its active nature and in the potential of controlling biological systems. PMID:25408720

Stoian, M; State, N; Stoica, V; Radulian, G

2014-01-01

97

LAbRAundA 2010 LARS KARLSSOn, JeSpeR bLId & OLIvIeR HenRy 19 LARS KARLSSOn, JeSpeR bLId & OLIvIeR HenRy  

E-print Network

LAbRAundA 2010 · LARS KARLSSOn, JeSpeR bLId & OLIvIeR HenRy · 19 LARS KARLSSOn, JeSpeR bLId & OLIv indicated a dating of the tower to about 380­350 BC. In the two additions to the tower, several well­13th-century date. Many marble pieces were retrieved from the marble furniture of the church, as well

Paris-Sud XI, Université de

98

Hindlimb suspension and SPE-like radiation impairs clearance of bacterial infections.  

PubMed

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health. PMID:24454913

Li, Minghong; Holmes, Veronica; Zhou, Yu; Ni, Houping; Sanzari, Jenine K; Kennedy, Ann R; Weissman, Drew

2014-01-01

99

Hindlimb Suspension and SPE-Like Radiation Impairs Clearance of Bacterial Infections  

PubMed Central

A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE)-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health. PMID:24454913

Li, Minghong; Holmes, Veronica; Zhou, Yu; Ni, Houping; Sanzari, Jenine K.; Kennedy, Ann R.; Weissman, Drew

2014-01-01

100

Evading apoptosis in cancer  

PubMed Central

Carcinogenesis is a mechanistically complex and variable process with a plethora of underlying genetic causes. Cancer development consists of a multitude of steps that occur progressively starting with initial driver mutation(s), to tumorigenesis, and ultimately metastasis. During these transitions, cancer cells accumulate a series of genetic alterations that confer upon the cells an unwarranted survival and proliferative advantage. During the course of development, however, cancer cells also encounter a physiologically ubiquitous cellular program that aims to eliminate damaged or abnormal cells: Apoptosis. Thus, it is essential that cancer cells acquire instruments to circumvent programmed cell death. Here we discuss emerging evidence indicating how cancer cells adopt various strategies to override apoptosis including amplifying the anti-apoptotic machinery, downregulating the pro-apoptotic program, or both. PMID:23958396

Fernald, Kaleigh

2013-01-01

101

Nanosized IrO 2 electrocatalysts for oxygen evolution reaction in an SPE electrolyzer  

Microsoft Academic Search

Nanosized IrO2 electrocatalysts (d ~ 7–9 nm) with specific surface area up to 100 m2 g?1 were synthesized and characterized for the oxygen evolution reaction in a solid polymer electrolyte (SPE) electrolyzer. The\\u000a catalysts were prepared by a colloidal method in aqueous solution and a subsequent thermal treatment. An iridium hydroxide\\u000a hydrate precursor was obtained at ~100 °C, which was, successively, calcined at different temperatures from

J. C. Cruz; V. Baglio; S. Siracusano; R. Ornelas; L. Ortiz-Frade; L. G. Arriaga; V. Antonucci; A. S. Aricò

2011-01-01

102

Foam Floatation-SPE for Separation and Concentration of Trace Ginsenosides  

Microsoft Academic Search

A foam floatation (FF) process and a solid phase extraction (SPE) process were synchronously applied to the separation and\\u000a concentration of ginsenosides from extracts of Panax quinquefolius L. The selectivity and sensitivity for the determination of the ginsenosides were improved. The experimental conditions,\\u000a including volumes of the sample solutions, pH value of sample solution, the flow rate of nitrogen gas

Rui Zhang; Hanqi Zhang; Liwei Wu; Jingyan You; Yuping Bai

2010-01-01

103

SPE-HPLC\\/DAD determination of trimethoprim, oxytetracycline and enrofloxacin in water samples  

Microsoft Academic Search

In this paper high-performance liquid chromatography with diode array UV detection (HPLC\\/DAD) after SPE sample pretreatment for simultaneous analysis of pharmaceuticals from three different classes: enrofloxacin, oxytetracycline and trimethoprim, has been developed, optimised and validated. The chromatographic separation was developed on spiked wellspring water samples and checked on model wastewater samples of veterinary pharmaceuticals before and after RO\\/NF membrane treatment

Danijela Ašperger; Sandra Babi?; Dragana Mutavdži? Pavlovi?; Davor Dolar; Krešimir Košuti?; Alka J. M. Horvat; Marija Kaštelan-Macan

2009-01-01

104

Mitochondria and Apoptosis  

NSDL National Science Digital Library

A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.

Douglas Green (La Jolla Institute for Allergy and Immunology; )

1998-08-28

105

Apoptosis in Cardiovascular Pathogenesis  

Microsoft Academic Search

The loss of cardiomyocytes in the human myocardium results in overloading of the heart, causing structural remodeling of the\\u000a heart and deterioration of the cardiac function, eventually leading to heart failure. Cellular suicide or apoptosis of cardiac\\u000a muscle cells has been identified as an essential process in the progression to heart failure. This process entails a highly\\u000a structured series of

Hamid el Azzouzi; Meriem Bourajjaj; Paula A. Martins; Leon J. Windt

106

Connective tissue growth factor mediates transforming growth factor b-induced collagen synthesis: down- regulation by cAMP  

Microsoft Academic Search

Connective tissue growth factor (CTGF) is a cysteine-rich peptide synthesized and secreted by fibroblastic cells after activation with transforming growth factor beta (TGF-b) that acts as a downstream mediator of TGF-b-induced fibroblast proliferation. We performed in vitro and in vivo studies to determine whether CTGF is also essential for TGF-b-induced fibroblast collagen synthesis. In vitro studies with normal rat kidney

MATTHEW R. DUNCAN; KEN S. FRAZIER; SUSAN ABRAMSON; SHAWN WILLIAMS; HELENE KLAPPER; XINFAN HUANG; GARY R. GROTENDORST

107

The Crystal Structure of Escherichia coli Spermidine Synthase SpeE Reveals a Unique Substrate-binding Pocket  

SciTech Connect

Polyamines are essential in all branches of life. Biosynthesis of spermidine, one of the most ubiquitous polyamines, is catalyzed by spermidine synthase (SpeE). Although the function of this enzyme from Escherichia coli has been thoroughly characterized, its structural details remain unknown. Here, we report the crystal structure of E. coli SpeE and study its interaction with the ligands by isothermal titration calorimetry and computational modelling. SpeE consists of two domains - a small N-terminal {beta}-strand domain, and a C-terminal catalytic domain that adopts a canonical methyltransferase (MTase) Rossmann fold. The protein forms a dimer in the crystal and in solution. Structural comparison of E. coli SpeE to its homologs reveals that it has a large and unique substrate-binding cleft that may account for its lower amine substrate specificity.

Zhou, X.; Chua, T; Tkaczuk, K; Bujnicki, J; Sivaraman, J

2010-01-01

108

Comparison of Radiation Transport Codes, HZETRN, HETC and FLUKA, Using the 1956 Webber SPE Spectrum  

NASA Technical Reports Server (NTRS)

Protection of astronauts and instrumentation from galactic cosmic rays (GCR) and solar particle events (SPE) in the harsh environment of space is of prime importance in the design of personal shielding, spacec raft, and mission planning. Early entry of radiation constraints into the design process enables optimal shielding strategies, but demands efficient and accurate tools that can be used by design engineers in every phase of an evolving space project. The radiation transport code , HZETRN, is an efficient tool for analyzing the shielding effectiveness of materials exposed to space radiation. In this paper, HZETRN is compared to the Monte Carlo codes HETC-HEDS and FLUKA, for a shield/target configuration comprised of a 20 g/sq cm Aluminum slab in front of a 30 g/cm^2 slab of water exposed to the February 1956 SPE, as mode led by the Webber spectrum. Neutron and proton fluence spectra, as well as dose and dose equivalent values, are compared at various depths in the water target. This study shows that there are many regions where HZETRN agrees with both HETC-HEDS and FLUKA for this shield/target configuration and the SPE environment. However, there are also regions where there are appreciable differences between the three computer c odes.

Heinbockel, John H.; Slaba, Tony C.; Blattnig, Steve R.; Tripathi, Ram K.; Townsend, Lawrence W.; Handler, Thomas; Gabriel, Tony A.; Pinsky, Lawrence S.; Reddell, Brandon; Clowdsley, Martha S.; Singleterry, Robert C.; Norbury, John W.; Badavi, Francis F.; Aghara, Sukesh K.

2009-01-01

109

Optimization and validation of organochlorine compounds in adipose tissue by SPE-gas chromatography.  

PubMed

Scientific evidence has shown an association between organochlorine compounds (OCC) exposure and human health hazards. Concerning this, OCC detection in human adipose samples has to be considered a public health priority. This study evaluated the efficacy of various solid-phase extraction (SPE) and cleanup methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped (C??-E), benzenesulfonic acid modified silica cation exchanger (SA), poly(styrene-divinylbenzene (EN) and EN/RP?? SPE sorbents were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture detection (GC-ECD). The C??-E columns with strong homogenization were found to provide the most effective cleanup, removing the greatest amount of interfering substance, and simultaneously ensuring good analyte recoveries higher than 70%. Recoveries?>?70% with standard deviations (SD)?

Fernandes, Virgínia C; Pestana, Diogo; Monteiro, Rosário; Faria, Gil; Meireles, Manuela; Correia-Sá, Luísa; Teixeira, Diana; Faria, Ana; Calhau, Conceição; Domingues, Valentina F; Delerue-Matos, Cristina

2012-12-01

110

SPE analysis of high efficiency PMTs for the DEAP-3600 dark matter detector  

NASA Astrophysics Data System (ADS)

The Dark matter Experiment using Argon Pulse-shape discrimination is a collaborative effort to develop a next-generation, tonne-scale dark matter detector at SNOLAB. The detector will feature a single-phase liquid argon (LAr) target surrounded by an array of 266 photomultiplier tubes (PMTs). A new high-efficiency Hamamatsu R877-100 PMT has been delivered to the University of Alberta for evaluation by the DEAP collaboration. The increase in efficiency could lead to a much greater light yield, but other experiments have reported a slower rise time [1],[2]. We have placed the PMT in a small dark box and had a base and preamplifier designed to be used with either an oscilloscope or a multi-channel analyzer. With this setup we have demonstrated the PMT's ability to distinguish single photo-electrons (SPE) and characterized the PMT by measuring the SPE pulse height spectrum, the peak-to-valley ratio, the dark pulse rate, the baseline, time resolution and SPE efficiency for varying the high voltage supplied to the PMT.

Olsen, Kevin; Hallin, Aksel; DEAP/CLEAN Collaboration

2011-09-01

111

SPE\\/TLC Profiling of the Impurities of MDMA: The Influence of an Agglutinant, Diluents, and Adulterants  

Microsoft Academic Search

The SPE\\/TLC method has been used in the screening profiling of impurities extracted (SPE) from MDMA (3,4?methylenedioxymethamphetamine), the main active component of Ecstasy tablets. Sought for, was the optimum buffer solution used in sample dissolution and optimum composition of eluent used in TLC separation. The spots of impurities were observed under UV light at ?exc=366 nm.The influence of magnesium stearate, used

J. Kochana; A. Parczewski; J. Wilamowski

2006-01-01

112

Diabetic myonecrosis in a patient with hepatitis B-induced liver cirrhosis.  

PubMed

Diabetic myonecrosis-a rare complication of long-standing, poorly controlled diabetes mellitus-typically presents with acute-onset muscle pain, is self-limiting, and responds well to conservative management. We report a case of diabetic myonecrosis in a 33-year-old man with hepatitis B-induced liver cirrhosis and type 2 diabetes who presented with abdominal distension and pain in the left thigh. Diabetic myonecrosis was diagnosed based on clinical presentation, radiological findings, magnetic resonance imaging and histopathological investigations; he was successfully treated conservatively with insulin and analgesics. Diabetic myonecrosis should be considered in the differential diagnosis of muscle pain in patients with diabetes. PMID:25305801

Park, Su Min; Kim, You Jeong; Kim, Seung Man; Han, Na; Lee, Eun Ju; Kim, Tae Kyoon; Kim, Tae Nyun; Kwon, Min Jeong; Kim, Mi Kyung; Lee, Soon Hee; Park, Jeong Hyun; Rhee, Byung Doo; Kim, Bo Mi; Lee, Sun Joo

2015-02-01

113

Galangin (3,5,7-trihydroxyflavone) shields human keratinocytes from ultraviolet B-induced oxidative stress.  

PubMed

Most skin damage caused by ultraviolet B (UVB) radiation is owing to the generation of reactive oxygen species. Phytochemicals can act as antioxidants against UVB-induced oxidative stress. This study investigated the protective effects of the flavone galangin against UVB-induced oxidative damage in human keratinocytes. Galangin efficiently scavenged free radicals and reduced UVB-induced damage to cellular macromolecules, such as DNA, lipids, and proteins. Furthermore, galangin rescued cells undergoing apoptosis induced by UVB radiation via recovering mitochondrial polarization and down-regulating apoptotic proteins. These results showed that galangin protects human keratinocytes against UVB radiation-induced cellular damage and apoptosis via its antioxidant effects. PMID:25767685

Madduma Hewage, Susara Ruwan Kumara; Piao, Mei Jing; Kim, Ki Cheon; Cha, Ji Won; Han, Xia; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

2015-03-01

114

Galangin (3,5,7-Trihydroxyflavone) Shields Human Keratinocytes from Ultraviolet B-Induced Oxidative Stress  

PubMed Central

Most skin damage caused by ultraviolet B (UVB) radiation is owing to the generation of reactive oxygen species. Phytochemicals can act as antioxidants against UVB-induced oxidative stress. This study investigated the protective effects of the flavone galangin against UVB-induced oxidative damage in human keratinocytes. Galangin efficiently scavenged free radicals and reduced UVB-induced damage to cellular macromolecules, such as DNA, lipids, and proteins. Furthermore, galangin rescued cells undergoing apoptosis induced by UVB radiation via recovering mitochondrial polarization and down-regulating apoptotic proteins. These results showed that galangin protects human keratinocytes against UVB radiation-induced cellular damage and apoptosis via its antioxidant effects. PMID:25767685

Madduma Hewage, Susara Ruwan Kumara; Piao, Mei Jing; Kim, Ki Cheon; Cha, Ji Won; Han, Xia; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

2015-01-01

115

A Novel Polyamine Allosteric Site of SpeG from Vibrio cholerae Is Revealed by Its Dodecameric Structure.  

PubMed

Spermidine N-acetyltransferase, encoded by the gene speG, catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria. In Escherichia coli, studies have shown that SpeG is the enzyme responsible for acetylating spermidine under stress conditions and for preventing spermidine toxicity. Not all bacteria contain speG, and many bacterial pathogens have developed strategies to either acquire or silence it for pathogenesis. Here, we present thorough kinetic analyses combined with structural characterization of the VCA0947 SpeG enzyme from the important human pathogen Vibrio cholerae. Our studies revealed the unexpected presence of a previously unknown allosteric site and an unusual dodecameric structure for a member of the Gcn5-related N-acetyltransferase superfamily. We show that SpeG forms dodecamers in solution and in crystals and describe its three-dimensional structure in several ligand-free and liganded structures. Importantly, these structural data define the first view of a polyamine bound in an allosteric site of an N-acetyltransferase. Kinetic characterization of SpeG from V. cholerae showed that it acetylates spermidine and spermine. The behavior of this enzyme is complex and exhibits sigmoidal curves and substrate inhibition. We performed a detailed non-linear regression kinetic analysis to simultaneously fit families of substrate saturation curves to uncover a simple kinetic mechanism that explains the apparent complexity of this enzyme. Our results provide a fundamental understanding of the bacterial SpeG enzyme, which will be key toward understanding the regulation of polyamine levels in bacteria during pathogenesis. PMID:25623305

Filippova, Ekaterina V; Kuhn, Misty L; Osipiuk, Jerzy; Kiryukhina, Olga; Joachimiak, Andrzej; Ballicora, Miguel A; Anderson, Wayne F

2015-03-27

116

Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell  

PubMed Central

Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-?-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 ?mol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

2013-01-01

117

p53 in neuronal apoptosis  

Microsoft Academic Search

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 can trigger apoptosis in many cell types including neurons. Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be responsible for neuronal deaths that occur in neurological disorders such

Carsten Culmsee; Mark P. Mattson

2005-01-01

118

Apoptosis and the Airway Epithelium  

PubMed Central

The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

White, Steven R.

2011-01-01

119

Estimates of HZE particle contributions to SPE radiation exposures on interplanetary missions  

NASA Technical Reports Server (NTRS)

Estimates of radiation doses resulting from possible HZE (high energy heavy ion) components of Solar Particle Events (SPEs) are presented for crews of manned interplanetary missions. The calculations assume a model spectrum obtained by folding measured solar flare HZE particle abundances with the measured energy spectra of SPE alpha particles. These hypothetical spectra are then transported through aluminum spacecraft shielding. The results, presented as estimates of absorbed dose and dose equivalent, indicate that HZE components by themselves are not a major concern for crew protection but should be included in any overall risk assessment. The predictions are found to be sensitive to the assumed spectral hardness parameters.

Townsend, L. W.; Cucinotta, F. A.; Wilson, J. W.; Bagga, R.

1994-01-01

120

Geologic Assessment of the Damage Zone from the Second Test at Source Physics Experiment-Nevada (SPE-N)  

SciTech Connect

The National Center for Nuclear Security, established by the U.S. Department of Energy, National Nuclear Security Administration (NNSA), is conducting a series of explosive tests at the Nevada National Security Site that are designed to increase the understanding of certain basic physical phenomena associated with underground explosions. These tests will aid in developing technologies that might be used to detect underground nuclear explosions in support of verification activities for the Comprehensive Nuclear-Test-Ban Treaty. The initial project is a series of explosive tests, known collectively as the Source Physics Experiment-Nevada (SPE-N), being conducted in granitic rocks. The SPE-N test series is designed to study the generation and propagation of seismic waves. The results will help advance the seismic monitoring capability of the United States by improving the predictive capability of physics-based modeling of explosive phenomena. The first SPE N (SPE-N-1) test was conducted in May 2011, using 100 kg of explosives at the depth of 54.9 m in the U 15n source hole. SPE-N-2 was conducted in October 2011, using 1,000 kg of explosives at the depth of 45.7 m in the same source hole. The SPE-N-3 test was conducted in the same source hole in July 2012, using the same amount and type of explosive as for SPE-N-2, and at the same depth as SPE-N-2, within the damage zone created by the SPE-N-2 explosion to investigate damage effects on seismic wave propagation. Following the SPE-N-2 shot and prior to the SPE-N-3 shot, the core hole U-15n#10 was drilled at an angle from the surface to intercept the SPE-N-2 shot point location to obtain information necessary to characterize the damage zone. The objective was to determine the position of the damage zone near the shot point, at least on the northeast, where the core hole penetrated it, and obtain information on the properties of the damaged medium. Geologic characterization of the post-SPE-N-2 core hole included geophysical logging, a directional survey, and geologic description of the core to document visual evidence of damage. Selected core samples were provided to Sandia National Laboratories (SNL) for measurement of physical and mechanical properties. A video was also run in the source hole after it was cleaned out. A significant natural fault zone was encountered in the angle core hole between 5.7 and 7.5 m from the shot point. However, several of the fractures observed in the core hole are interpreted as having been caused by the explosion. The fractures are characterized by a “fresh,” mechanically broken look, with uncoated and very irregular surfaces. They tend to terminate against natural fractures and have orientations that differ from the previously defined natural fracture sets; they are common starting at about 5.4 m from the shot point. Within about 3.3 m of the shot point to the end of the recovered core at 1.6 m from the shot point, some of the core samples are softer and lighter in color, but do not appear to be weathered. It is thought this could be indicative of the presence of distributed microfracturing.

Townsend, M. J.; Huckins-Gang, H. E.; Prothro, L. B.; Reed, D. N.

2012-12-01

121

Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans  

PubMed Central

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NF?B induction. Proteins involved in apoptosis and NF?B induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NF?B-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families. PMID:12819136

Reed, John C.; Doctor, Kutbuddin; Rojas, Ana; Zapata, Juan M.; Stehlik, Christian; Fiorentino, Loredana; Damiano, Jason; Roth, Wilfried; Matsuzawa, Shu-ichi; Newman, Ruchi; Takayama, Shinichi; Marusawa, Hiroyuki; Xu, Famming; Salvesen, Guy; Godzik, Adam

2003-01-01

122

SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines  

PubMed Central

Background CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP–10/CXCL10 and I–TAC/CXCL11, are antibacterial for Streptococcus pyogenes. Methodology/Principal Findings SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GRO?/CXCL1, GRO?/CXCL2, GRO?/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3?/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3?/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. Conclusions/Significance SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium. PMID:19274094

Egesten, Arne; Olin, Anders I.; Linge, Helena M.; Yadav, Manisha; Mörgelin, Matthias; Karlsson, Anna; Collin, Mattias

2009-01-01

123

Recent improvements in SPE3D: a VR-based surgery planning environment  

NASA Astrophysics Data System (ADS)

SPE3D is a surgery planning environment developed within TLEMsafe project [1] (funded by the European Commission FP7). It enables the operator to plan a surgical procedure on the customized musculoskeletal (MS) model of the patient's lower limbs, send the modified model to the biomechanical analysis module, and export the scenario's parameters to the surgical navigation system. The personalized patient-specific three-dimensional (3-D) MS model is registered with 3-D MRI dataset of lower limbs and the two modalities may be visualized simultaneously. Apart from main planes, any arbitrary MRI cross-section can be rendered on the 3-D MS model in real time. The interface provides tools for: bone cutting, manipulating and removal, repositioning muscle insertion points, modifying muscle force, removing muscles and placing implants stored in the implant library. SPE3D supports stereoscopic viewing as well as natural inspection/manipulation with use of haptic devices. Alternatively, it may be controlled with use of a standard computer keyboard, mouse and 2D display or a touch screen (e.g. in an operating room). The interface may be utilized in two main fields. Experienced surgeons may use it to simulate their operative plans and prepare input data for a surgical navigation system while student or novice surgeons can use it for training.

Witkowski, Marcin; Sitnik, Robert; Verdonschot, Nico

2014-02-01

124

Cotton HILIC SPE microtips for microscale purification and enrichment of glycans and glycopeptides.  

PubMed

Solid-phase extraction microtips are important devices in modern bioanalytics, as they allow miniaturized sample preparation for mass spectrometric analysis. Here we introduce the use of cotton wool for the preparation of filter-free HILIC SPE microtips. To this end, pieces of cotton wool pads (approximately 500 ?g) were packed into 10 ?L pipet tips. The performance of the tips was evaluated for microscale purification of tryptic IgG Fc N-glycopeptides. Cotton wool HILIC SPE microtips allowed the removal of salts, most nonglycosylated peptides, and detergents such as SDS from glycoconjugate samples. MALDI-TOF-MS glycopeptide profiles were very repeatable with different tips as well as reused tips, and very similar profiles were obtained with different brands of cotton wool pads. In addition, we used cotton HILIC microtips to purify N-glycans after N-glycosidase F treatment of IgG and transferrin followed by MALDI-TOF-MS detection. In conclusion, we establish cotton wool microtips for glycan and glycopeptide purification with subsequent mass spectrometric detection. PMID:21366235

Selman, Maurice H J; Hemayatkar, Mahdi; Deelder, André M; Wuhrer, Manfred

2011-04-01

125

Systematic optimization of an SPE with HPLC-FLD method for fluoroquinolone detection in wastewater.  

PubMed

This paper describes a selective and ultra-sensitive analytical method for simultaneous determination of 11 fluoroquinolone (FQ) antibiotics in environmental and wastewater samples. The method employs offline solid-phase extraction (SPE) and reversed-phase high performance liquid chromatography with fluorescence detection (HPLC-FLD). A weak cation exchange SPE protocol was developed with a novel loading volume optimization algorithm and a methanol cleanup step to remove background organic matter. Various parameters were optimized to recover FQs from water/wastewater and analyte recovery was generally greater than 80%. Chromatographic separation of the 11 FQs was achieved on a 150 mm pentafluorophenyl column using a gradient elution scheme with methanol, acetonitrile, and 20mM phosphate buffer (pH=2.4). Excitation and emission wavelengths were individually optimized for each FQ using fluorescence spectroscopy; the excitation and emission wavelengths were 276-296 nm and 444-506 nm, respectively. Instrumental quantitation limits were 20-100 pg of mass injected. Of the 11 FQs investigated, seven (i.e., ciprofloxacin, difloxacin, enrofloxacin, fleroxacin, norfloxacin, moxifloxacin, and ofloxacin) were detected during a four-month sampling campaign of wastewater and wastewater-impacted surface water. Concentrations of FQs in raw wastewater, wastewater effluent, and wastewater-impacted surface water were 5-1292, 2-504, and 4-187ng/L, respectively. PMID:25200119

He, Ke; Blaney, Lee

2015-01-23

126

Design and test status for life support applications of SPE oxygen generation systems. [Solid Polymer Electrolyte  

NASA Technical Reports Server (NTRS)

An advanced six-man rated oxygen generation system has been fabricated and tested as part of a NASA/JSC technology development program for a long lived, manned spacecraft life support system. Details of the design and tests results are presented. The system is based on the Solid Polymer Electrolyte (SPE) water electrolysis technology and its nominal operating conditions are 2760 kN/sq m (400 psia) and 355 K (180 F) with an electrolysis module current density capability up to 350 mA/sq cm (326 ASF). The system is centered on a 13-cell SPE water electrolysis module having a single cell active area of 214 sq cm (33 sq in) and it incorporates instrumentation and controls for single pushbutton automatic startup/shutdown, component fault detection and isolation, and self-contained sensors and controls for automatic safe emergency shutdown. The system has been tested in both the orbital cyclic and continuous mode of operation. Various parametric tests have been completed to define the system capability for potential application in spacecraft environmental systems.

Titterington, W. A.; Erickson, A. C.

1975-01-01

127

Keratinocyte Apoptosis in Epidermal Development and Disease  

Microsoft Academic Search

Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restraining carcinogenesis. Apoptosis balances proliferation to maintain epidermal thickness, contributes to stratum corneum formation and may eliminate pre-malignant cells. Apart from the normal developmental program, KC apoptosis can be triggered by UV light and other stimuli. Dysfunctional apoptosis occurs in some skin diseases, such as psoriasis and skin

Deepak Raj; Douglas E Brash; Douglas Grossman

2006-01-01

128

APOPTOSIS IN WHOLE MOUSE OVARIES  

EPA Science Inventory

Apoptosis in Whole Mouse Ovaries Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711....

129

Invertebrate Iridovirus modulation of apoptosis  

Microsoft Academic Search

Programmed cell death (apoptosis) is a key host response to virus infection. Viruses that can modulate host apoptotic responses\\u000a are likely to gain important opportunities for transmission. Here we review recent studies that demonstrate that particles\\u000a of Invertebrate iridescent virus 6 (IIV-6) (Iridoviridae, genus Iridovirus), or an IIV-6 virion protein extract, are capable of inducing apoptosis in lepidopteran and coleopteran

Trevor Williams; Nilesh S. Chitnis; Shän L. Bilimoria

2009-01-01

130

Analgesic efficacy of sodium salicylate in an amphotericin B-induced bovine synovitis-arthritis model.  

PubMed

This study examined the efficacy of sodium salicylate for providing analgesia in an amphotericin B-induced bovine synovitis-arthritis model using 10 male Holstein calves, 4 to 6 mo old and weighing approximately 250 kg. The study used a repeated measures partial crossover design with 2 phases, consisting of 3 treatment periods within each phase. Calves were blocked by body weight and randomly assigned to the sodium salicylate (50 mg/kg i.v.) or placebo group for phase 1. In period 1, lameness induction was simulated with a needle prick of the coronary band, followed by drug or placebo administration. At predetermined time points, serial blood samples for cortisol and salicylate concentrations, electrodermal activity measurements, heart rates, and pressure mat data were collected. Visual lameness scores were recorded by an observer blinded to treatments. In period 2, lameness was induced with injection of amphotericin B into the distal interphalangeal joint, followed by drug or placebo administration, with sample collection as described previously. In period 3, the drug or placebo was administered to the respective calves with sample collection. After a 10-d washout period, phase 2 was conducted with treatments crossed over between groups. Cortisol and salicylate samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay, respectively. The pharmacokinetic data were analyzed using compartmental analysis. Mean intravenous salicylate apparent volume of distribution was 0.2 +/- 0.005 L/kg, total body clearance was 4.3 +/- 0.2 mL/min.kg, and elimination half-life was 36.9 +/- 1.2 min. The repeated measures data were analyzed based on a univariate split-plot approach with a random effects-mixed model. Differences in stance phase duration and serum cortisol concentration values were seen both between periods and between treatment group x periods; differences in heart rate, contact surface area, and contact pressure values were seen between periods, suggesting that our lameness model was effective. No differences were seen between treatment groups. When analyzed by visual lameness score, differences were seen in heart rate, contact surface area, contact pressure, and cortisol concentrations. Area under the time-effect curves, determined by using the trapezoidal rule, had results similar to the repeated measures data, except for a difference in period for electrodermal activity. This amphotericin B-induced synovitis-arthritis model is a useful tool for studying changes associated with lameness in cattle. Sodium salicylate was not effective in providing analgesia after lameness. PMID:19620655

Kotschwar, J L; Coetzee, J F; Anderson, D E; Gehring, R; KuKanich, B; Apley, M D

2009-08-01

131

?FosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line  

Microsoft Academic Search

The fates of Rat1a cells expressing FosB and ?FosB as fusion proteins (ER-FosB, ER-?FosB) with the ligand binding domain of human estrogen receptor were examined. The binding of estrogen to the fusion proteins resulted in their nuclear translocation and triggered cell proliferation, and thereafter delayed cell death was observed only in cells expressing ER-?FosB. The proliferation of Rat1a cells, but

K Tahara; D Tsuchimoto; Y Tominaga; S Asoh; S Ohta; M Kitagawa; H Horie; T Kadoya; Y Nakabeppu

2003-01-01

132

NF-?B-Inducing Kinase Regulates Selected Gene Expression in the Nod2 Signaling Pathway  

PubMed Central

The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-?B pathway. It has been suggested through indirect studies that NF-?B-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK?/? mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense. PMID:16552041

Pan, Qilin; Kravchenko, Vladimir; Katz, Alex; Huang, Shuang; Ii, Masayuki; Mathison, John C.; Kobayashi, Koichi; Flavell, Richard A.; Schreiber, Robert D.; Goeddel, David; Ulevitch, Richard J.

2006-01-01

133

Ram ion scattering caused by space shuttle v times B induced differential charging  

SciTech Connect

Observations of secondary, high-inclination ions streams have been reported in the literature. The authors of these previous papers attributed the source of the secondary ions to a disturbed region in the plasma about 10 m form the space shuttle Orbiter. A new theory has been developed which shows how v {times} B induces differential charging on the plasma diagnostics package (PDP) can scatter the ram ion flux. Some of these ions are reflected back to the PDP and may be the source of the observed ion distributions. The effect is unique to large spacecraft; it occurs only when the magnitude of the induced v {times} B potentials are much larger than the electron thermal energy and of the order of the ion ram energy. That the ion streams observed at large angles must have been reflected from the PDP surface is demonstrated with three-dimensional sheath and particle trajectory calculations using the low earth orbit version of the NASA Charging Analyzer Program (NASCAP/LEO).

Katz, I.; Davis, V.A. (S-Cubed Div. of Maxwell Labs., La Jolla, CA (United States))

1987-08-01

134

Ram ion scattering caused by Space Shuttle v x B induced differential charging  

NASA Technical Reports Server (NTRS)

Observations of secondary, high-inclination ions streams have been reported in the literature. The authors of these previous papers attributed the source of the secondary ions to a disturbed region in the plasma about 10 m from the Space Shuttle Orbiter. A new theory has been developed which shows how v x B induced differential charging on the plasma diagnostics package (PDP) can scatter the ram ion flux. Some of these ions are reflected back to the PDP and may be the sorce of the observed ion distributions. The effect is unique to large spacecraft; it occurs only when the magnitude of the induced v x B potentials are much larger than the electron thermal energy and of the order of the ion ram energy. That the ion streams observed at large angles must have been reflected from the PDP surface is demonstrated with three-dimensional sheath and particle trajectory calculations using the low earth orbit version of the NASA Charging Analyzer Program (NASCAP/LEO).

Katz, I.; Davis, V. A.

1987-01-01

135

Determination of gadolinium in river water by SPE preconcentration and ICP-MS.  

PubMed

An analytical scheme was developed for the determination of Gd-diethylenetriaminepentaacetate (Gd-DTPA), Gd and the other rare earth elements (REE) in river water by inductively coupled plasma (quadrupole) mass spectrometry (ICP-Q-MS). The preconcentration step was essential, since the limits of detection of this multielemental analytical technique are higher than the trace concentrations of the interesting elements in river water. Solid phase extraction (SPE) with different commercially available complexing agents (Chelex 100, Toyopearl and ethylhexylphosphates) was employed for the preconcentration of REE. The investigations revealed that complex stability (varying in dependence of the pH value) has a strong influence on the degree of the enrichment of Gd-DTPA. Based on acidified water samples (pH<3) a procedure using ethylhexylphosphates was proposed for the preconcentration of Gd and REE from surface water samples. For this purpose C(18)-cartridges loaded with ethylhexylphosphates were used, resulting in an enrichment factor of 40. PMID:18969433

Hennebrüder, Kristina; Wennrich, Rainer; Mattusch, Jürgen; Stärk, Hans-Joachim; Engewald, Werner

2004-05-28

136

SPE-LC-FD determination of polycyclic aromatic hydrocarbon monohydroxy derivatives in cephalopods.  

PubMed

A new analytical methodology, based on liquid chromatography with fluorescence detection (LC-FD), after extraction, enzymatic hydrolysis, and solid-phase extraction (SPE) through Oasis HLB cartridges, was developed and validated for the simultaneous determination of three monohydroxy derivatives of polycyclic aromatic hydrocarbons (PAHs). The optimized analytical method is sensitive, accurate, and precise, with recoveries between 62 and 110% and limits of detection of 227, 9, and 45 ng/g for 1-hydroxynaphthalene, 2-hydroxyfluorene, and 1-hydroxypyrene, respectively. Their levels were estimated in different cephalopod matrices (edible tissues and hemolymph). The methodology was applied to samples of the major cephalopod species consumed worldwide. Of the 18 samples analyzed, 39% were contaminated with 1-hydroxynaphthalene, which was the only PAH metabolite detected. Its concentration ranged from 786 to 1145 ng/g. This highly sensitive and specific method allows the identification and quantitation of PAH metabolites in forthcoming food safety and environmental monitoring programs. PMID:24588515

Lourenço, Diana; Silva, Liliana J G; Lino, Celeste M; Morais, Simone; Pena, Angelina

2014-03-26

137

E D I T O R I A L his month's issue of Nature Immunology includes a spe-  

E-print Network

E D I T O R I A L T his month's issue of Nature Immunology includes a spe- cial focus on Chromatin Dynamics in the Immune System. A comprehensive overview and four review arti- cles demystify the molecular/special_focus/chromatin_dynamics/), free until September, contains additional features and online-only links, contributed by immunology

Cai, Long

138

HybridSPE: A novel technique to reduce phospholipid-based matrix effect in LC–ESI-MS Bioanalysis  

PubMed Central

When complex biological materials are analyzed without an adequate sample preparation technique, MS signal and response undergo significant alteration and result in poor quantification and assay. This problem generally takes place due to the presence of several endogenous materials component in samples. One of the major causes of ion suppression in bioanalysis is the presence of phospholipids during LC-MS analysis. The phospholipid-based matrix effect was investigated with a commercially available electro spray ionization (ESI) source coupled with a triple quadrupole mass spectrometer. HybridSPE dramatically reduced the levels of residual phospholipids in biological samples, leading to significant reduction in matrix effects. This new procedure that combines the simplicity of precipitation with the selectivity of SPE allows obtaining much cleaner extracts than with conventional procedures. HybridSPE-precipitation procedure provides significant improvement in bioanalysis and a practical and fast way to ensure the avoidance of phospholipids-based matrix effects. The present review outlines the HybridSPE technique to minimize phospholipids-based matrix effects on LC–ESI-MS bioanalysis. PMID:23248558

Ahmad, Shafeeque; Kalra, Harsh; Gupta, Amit; Raut, Bharat; Hussain, Arshad; Rahman, Md. Akhlaquer

2012-01-01

139

Near-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution of Ices  

E-print Network

Near-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution and evolution of Triton's ices Manuscript pages: 51 Figures: 11 Tables: 5 #12;­ 2 ­ ABSTRACT This report arises from an ongoing program to monitor Neptune's largest moon Triton spectroscopically in the 0.8 to 2.4 µm

Young, Leslie A.

140

Characteristics of Four SPE Classes According to Onset Timing and Proton Acceleration Patterns  

NASA Astrophysics Data System (ADS)

In our previous work (Kim et al., 2015), we suggested a new classification scheme, which categorizes the SPEs into four groups based on association with flare or CME inferred from onset timings as well as proton acceleration patterns using multienergy observations. In this study, we have tried to find whether there are any typical characteristics of associated events and acceleration sites in each group using 42 SPEs from 1997 to 2012. We find: (i) if the proton acceleration starts from a lower energy, a SPE has a higher chance to be a strong event (> 5000 pfu) even if the associated flare and CME are not so strong. The only difference between the SPEs associated with flare and CME is the location of the acceleration site. For the former, the sites are very low ( ~1 Rs) and close to the western limb, while the latter has a relatively higher (mean=6.05 Rs) and wider acceleration sites. (ii) When the proton acceleration starts from the higher energy, a SPE tends to be a relatively weak event (< 1000 pfu), in spite of its associated CME is relatively stronger than previous group. (iii) The SPEs categorized by the simultaneous proton acceleration in whole energy range within 10 minutes, tend to show the weakest proton flux (mean=327 pfu) in spite of strong related eruptions. Their acceleration heights are very close to the locations of type II radio bursts. Based on those results, we suggest that the different characteristics of the four groups are mainly due to the different mechanisms governing the acceleration pattern and interval, and different condition such as the acceleration location.

Kim, Roksoon

2015-04-01

141

Optimization of an SPE and GC/MS Method for Analyzing Endocrine Disrupting Compounds in Water  

NASA Astrophysics Data System (ADS)

Endocrine disrupting compounds (EDCs) are compounds that interrupt hormonal functions in the body. The literature reports the presence of EDCs in all environmental matrices (air, water and soil) at concentrations of at least 1 nanogram/liter (ng/l), which may be high enough to induce adverse health effects. Therefore, reliable analytical methods for detecting trace amounts of EDCs in water is very important for investigating and controlling their concentrations in the environment. This study investigated a method for analyzing four known or suspected EDCs (chlorpyrifos, musk HHCB, diethyl phthalate, and butylated hydroxyanisole) in water samples. The analytical method was based on the USGS wastewater method developed by Zaugg et al. (2001), but modified, using solid phase extraction (SPE) followed by gas chromatography and mass spectrometry (GC/MS) analysis. The EDCs were extracted using 60mg Water Oasis hydrophilic-lipophillic balance (HLB) extraction cartridges. The SPE efficiency was investigated by using different initial extraction volumes and different EDC concentrations. The lowest concentration was 1ng/l and the lowest extraction volume was 100mL. Results of the study indicate that the initial oven temperature conditions and rate of temperature increases affects the peak signal to noise ratio and the sample run-time in the GC/MS. An increase in gas flow rate did not show any significant changes and hence was maintained at 1ml/min. Preliminary data suggests that the percent recovery of the compounds obtained using this method either met or exceeded those presented by Zaugg et al. (2001) as the USGS wastewater method.

Thomas, S. M.; Bodour, A.; Murray, K. E.

2006-12-01

142

Application of Nanofiber-packed SPE for Determination of Urinary 1-Hydroxypyrene Level Using HPLC.  

PubMed

It is always desirable to achieve maximum sample clean-up, extraction, and pre-concentration with the minimum possible organic solvent. The miniaturization of sample preparation devices was successfully demonstrated by packing 10 mg of 11 electrospun polymer nanofibers into pipette tip micro column and mini disc cartridges for efficient pre-concentration of 1-hydroxypyrene in urine samples. 1-hydroxypyrene is an extensively studied biomarker of the largest class of chemical carcinogens. Excretory 1-hydroxypyrene was monitored with HPLC/fluorescence detector. Important parameters influencing the percentage recovery such as fiber diameter, fiber packing amount, eluent, fiber packing format, eluent volume, surface area, porosity, and breakthrough parameters were thoroughly studied and optimized. Under optimized condition, there was a near perfect linearity of response in the range of 1-1000 ?g/L with a coefficient of determination (r (2)) between 0.9992 and 0.9999 and precision (% RSD) ?7.64% (n = 6) for all the analysis (10, 25, and 50 ?g/L). The Limit of detection (LOD) was between 0.022 and 0.15 ?g/L. When compared to the batch studies, both disc packed nanofiber sorbents and pipette tip packed sorbents exhibited evident dominance based on their efficiencies. The experimental results showed comparable absolute recoveries for the mini disc packed fibers (84% for Nylon 6) and micro columns (80% for Nylon 6), although the disc displayed slightly higher recoveries possibly due to the exposure of the analyte to a larger reacting surface. The results also showed highly comparative extraction efficiencies between the nanofibers and conventional C-18 SPE sorbent. Nevertheless, miniaturized SPE devices simplified sample preparation, reducing back pressure, time of the analysis with acceptable reliability, selectivity, detection levels, and environmental friendliness, hence promoting green chemistry. PMID:24812483

Ifegwu, Okechukwu Clinton; Anyakora, Chimezie; Chigome, Samuel; Torto, Nelson

2014-01-01

143

Application of Nanofiber-packed SPE for Determination of Urinary 1-Hydroxypyrene Level Using HPLC  

PubMed Central

It is always desirable to achieve maximum sample clean-up, extraction, and pre-concentration with the minimum possible organic solvent. The miniaturization of sample preparation devices was successfully demonstrated by packing 10 mg of 11 electrospun polymer nanofibers into pipette tip micro column and mini disc cartridges for efficient pre-concentration of 1-hydroxypyrene in urine samples. 1-hydroxypyrene is an extensively studied biomarker of the largest class of chemical carcinogens. Excretory 1-hydroxypyrene was monitored with HPLC/fluorescence detector. Important parameters influencing the percentage recovery such as fiber diameter, fiber packing amount, eluent, fiber packing format, eluent volume, surface area, porosity, and breakthrough parameters were thoroughly studied and optimized. Under optimized condition, there was a near perfect linearity of response in the range of 1–1000 ?g/L with a coefficient of determination (r2) between 0.9992 and 0.9999 and precision (% RSD) ?7.64% (n = 6) for all the analysis (10, 25, and 50 ?g/L). The Limit of detection (LOD) was between 0.022 and 0.15 ?g/L. When compared to the batch studies, both disc packed nanofiber sorbents and pipette tip packed sorbents exhibited evident dominance based on their efficiencies. The experimental results showed comparable absolute recoveries for the mini disc packed fibers (84% for Nylon 6) and micro columns (80% for Nylon 6), although the disc displayed slightly higher recoveries possibly due to the exposure of the analyte to a larger reacting surface. The results also showed highly comparative extraction efficiencies between the nanofibers and conventional C-18 SPE sorbent. Nevertheless, miniaturized SPE devices simplified sample preparation, reducing back pressure, time of the analysis with acceptable reliability, selectivity, detection levels, and environmental friendliness, hence promoting green chemistry. PMID:24812483

Ifegwu, Okechukwu Clinton; Anyakora, Chimezie; Chigome, Samuel; Torto, Nelson

2014-01-01

144

Bovine lactoferricin causes apoptosis in Jurkat T-leukemia cells by sequential permeabilization of the cell membrane and targeting of mitochondria  

SciTech Connect

Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that kills Jurkat T-leukemia cells by the mitochondrial pathway of apoptosis. However, the process by which LfcinB triggers mitochondria-dependent apoptosis is not well understood. Here, we show that LfcinB-induced apoptosis in Jurkat T-leukemia cells was preceded by LfcinB binding to, and progressive permeabilization of the cell membrane. Colloidal gold electron microscopy revealed that LfcinB entered the cytoplasm of Jurkat T-leukemia cells prior to the onset of mitochondrial depolarization. LfcinB was not internalized by endocytosis because endocytosis inhibitors did not prevent LfcinB-induced cytotoxicity. Furthermore, intracellular delivery of LfcinB via fusogenic liposomes caused the death of Jurkat T-leukemia cells, as well as normal human fibroblasts. Collectively, these findings suggest that LfcinB caused damage to the cell membrane that allowed LfcinB to enter the cytoplasm of Jurkat T-leukemia cells and mediate cytotoxicity. In addition, confocal microscopy showed that intracellular LfcinB co-localized with mitochondria in Jurkat T-leukemia cells, while flow cytometry and colloidal gold electron microscopy showed that LfcinB rapidly associated with purified mitochondria. Furthermore, purified mitochondria treated with LfcinB rapidly lost transmembrane potential and released cytochrome c. We conclude that LfcinB-induced apoptosis in Jurkat T-leukemia cells resulted from cell membrane damage and the subsequent disruption of mitochondrial membranes by internalized LfcinB.

Mader, Jamie S. [Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Richardson, Angela [Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Salsman, Jayme [Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Top, Deniz [Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Antueno, Roberto de [Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Duncan, Roy [Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada); Hoskin, David W. [Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada) and Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1X5 (Canada)]. E-mail: d.w.hoskin@dal.ca

2007-07-15

145

SPE-HPLC purification of endocrine-disrupting compounds from human serum for assessment of xenoestrogenic activity.  

PubMed

Assessment of xenoestrogenic activity in human serum samples requires the removal of endogenous sex hormones to assure that the activity measured originates from xenobiotic compounds only. Serum samples representing high, medium and lower accumulation of persistent organic pollutants (POPs) were extracted using solid-phase extraction (SPE) followed by normal-phase high-performance liquid chromatography (NP-HPLC) for separation of POPs from endogenous hormones. The recovery of polychlorinated biphenyl (PCB) congeners in spiked serum samples was up to 86 %, making the extraction method suitable for the study. MVLN cells, stably transfected with an estrogen receptor (ER) luciferase reporter vector (estrogen response element chemically activated luciferase expression, ERE-CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of the integrated estrogenic activity. The effects of PCBs were analyzed by direct in vitro exposure of PCBs (nos. 138, 153, 180) and by ex vivo analysis of SPE-HPLC extracts from serum spiked with the PCBs. Similar effects on ER transactivation were observed for the direct in vitro and the ex vivo analysis experiments. The ER transactivation responses determined for actual serum samples were in the linear range of the dose-response curve. 17beta-Estradiol titrations showed that the xenoestrogenic effects were mediated via ER. Moreover, our SPE-HPLC-ERE-CALUX assay was demonstrated to elicit high interlaboratory correlation. In the present study the combination of SPE-HPLC purification and the ex vivo estrogenic responses measured by ERE-CALUX was validated and considered to be a valuable tool to assess the combined ER effect of lipophilic serum POPs where additive/synergistic and agonistic/antagonistic effects are integrated giving an overall estimate of exposure and bioactivity. PMID:16791568

Hjelmborg, Philip Sebastian; Ghisari, Mandana; Bonefeld-Jorgensen, Eva Cecilie

2006-07-01

146

Molecular mechanisms of hepatic apoptosis  

PubMed Central

Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis. PMID:24434519

Wang, K

2014-01-01

147

Caffeic Acid Phenethyl Ester Protects against Amphotericin B Induced Nephrotoxicity in Rat Model  

PubMed Central

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10??mol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50?mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10??mol/kg CAPE i.p. and one dose of 50?mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models. PMID:25032223

Altunta?, Atila; Y?lmaz, H. Ramazan; Altunta?, Ay?egül; Uz, Efkan; Demir, Murat; Gökçimen, Alparslan; Aksu, O?uzhan; Bayram, Dilek ?enol; Sezer, Mehmet Tu?rul

2014-01-01

148

The kinetics of UV-B induced photoinhibition of photosynthesis in the context of vertical mixing  

SciTech Connect

The effect of ultraviolet radiation on primary productivity is conventionally assessed by putting natural samples in containers with different transmission characteristics and measuring the effects of specified wavebands on the uptake of [sup 14]C-bicarbonate. In the marine environment, the waveband of principal importance is the middle ultraviolet (UV-B). Because the time scale of the experiment may not match the time scale of vertical mixing, it is implicitly or explicitly assumed that the relative reduction of photosynthesis associated with UV-B is independent of the duration of exposure. It this were true, vertical mixing in the surface layer of the sea would not change the effect of ultraviolet radiation on integral photosynthesis, even though it would have a profound effect on the per-cell exposures to UV. These assumptions are not supported for photoinhibition of photosynthesis by visible light, but the question is unresolved for UV-B. Here we examine the assumptions underlying the experimental assessment of photoinhibition in nature, with particular emphasis on the kinetics of UV-B induced photoinhibition of photosynthesis. It is shown that if photoinhibition is modeled as dose-dependent reduction in the instantaneous rate of photosynthesis, the relative reduction of [sup 14]C-bicarbonate uptake associated with UV-B exposure will increase with time. If, as suggested by published results, the process of photoinhibition is a function of irradiance as well as dose, models and interpretations become more complicated. We use previously published and new experimental results to demonstrate how experiments can overestimate UV-induced photoinhibition when incubation time is longer than the temporal scale of vertical mixing.

Lesser, M.P.; Cullen, J.J. (Bigelow Lab. for Ocean Sciences, W. Boothbay Harbor, ME (United States))

1990-01-09

149

Polymyxin B induces transient permeability fluctuations in asymmetric planar lipopolysaccharide/phospholipid bilayers.  

PubMed

The interaction of the polycationic decapeptide polymyxin B with asymmetric planar bilayers from lipopolysaccharide and phospholipid monolayers, which resemble the lipid matrix of the outer membrane of Gram-negative bacteria, was investigated. The addition of polymyxin B in micromolar amounts to the lipopolysaccharide side of the asymmetric bilayers resulted, under voltage-clamp conditions, in a fast macroscopic increase of their ionic conductance, whereas the polymyxin B nonapeptide induced no significant conductance changes. The polymyxin B induced macroscopic conductance exhibited large fluctuations and was strongly dependent on the amplitude and polarity of the transmembrane potential. The temporal pattern and amplitudes of the fluctuations were characterized by power spectra of the membrane currents and their variances, respectively. In the initial phase following peptide addition, the conductance changes appeared to be channellike discrete fluctuations. The lifetimes of the fluctuations were exponentially distributed, and the mean lifetimes were strongly voltage-dependent, ranging from approximately 30 ms at +80 mV (positive at the side opposite to peptide addition) to less than 5 ms at reverse polarity. The conductance amplitudes of the single fluctuations exhibited a broad distribution with a mean of 2 nS. A comparison of the features of the macroscopic conductance and of the discrete fluctuations showed that the former can basically be understood as a superposition of a large number of the latter. From the amplitudes of the fluctuations, the diameter of the polymyxin-induced lesions was estimated to about 3 nm. The experimental findings can be understood by assuming a detergent-like action of polymyxin B. PMID:1731918

Schröder, G; Brandenburg, K; Seydel, U

1992-01-28

150

The mechanism of PDT-induced apoptosis  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) can induce apoptosis in many cancer cells in vitro and in tumors in vivo. Cells become more oxidation with PDT, and maintain differentiation and proliferation, go apoptosis and necrosis with the increase of reactive oxygen species (ROS) concentration. ROS can induce apoptosis through mitochondria by inhibiting respiration chain or oxidative phosphorylation or damaging mitochondrial membrane. ROS can initiate apoptosis through endoplamic reticulum(ER) by opening Ca2+ channel or starting unfold protein response (UPR). ROS can also induce apoptosis through Golgi by producing ganglioside GD3 by use of ceramide, which induces apoptosis by activating caspase-3, JNK and p38 MAPK. It can also induce apoptosis by activating Bip (mitochondria-dependant) or preocaspase-12 (mitochondria- independent) or inhibiting protein synthesizing. There are so complicated cross-talking among different signal pathways or organnells that we think PDT-induced apoptosis is mediated by multiplex pathways and excessive levels in a refined network.

Cai, Xiongwei; Liu, Timon C.; Ding, Xin-Min; Gu, Ying; Liu, Fan-Guang; Liu, Song-Hao

2003-12-01

151

The Development and Optimization of Techniques for Monitoring Water Quality on-Board Spacecraft Using Colorimetric Solid-Phase Extraction (C-SPE)  

SciTech Connect

The main focus of this dissertation is the design, development, and ground and microgravity validation of methods for monitoring drinking water quality on-board NASA spacecraft using clorimetric-solid phase extraction (C-SPE). The Introduction will overview the need for in-flight water quality analysis and will detail some of the challenges associated with operations in the absence of gravity. The ability of C-SPE methods to meet these challenges will then be discussed, followed by a literature review on existing applications of C-SPE and similar techniques. Finally, a brief discussion of diffuse reflectance spectroscopy theory, which provides a means for analyte identification and quantification in C-SPE analyses, is presented. Following the Introduction, four research chapters are presented as separate manuscripts. Chapter 1 reports the results from microgravity testing of existing C-SPE methods and procedures aboard NASA's C-9 microgravity simulator. Chapter 2 discusses the development of a C-SPE method for determining the total concentration of biocidal silver (i.e., in both dissolved and colloidal forms) in water samples. Chapter 3 presents the first application of the C-SPE technique to the determination of an organic analyte (i.e., formaldehyde). Chapter 4, which is a departure from the main focus of the thesis, details the results of an investigation into the effect of substrate rotation on the kinetics involved in the antigen and labeling steps in sandwich immunoassays. These research chapters are followed by general conclusions and a prospectus section.

April Hill

2007-12-01

152

Activation of transient receptor potential melastatin 8 reduces ultraviolet B-induced prostaglandin E2 production in keratinocytes.  

PubMed

Transient receptor potential melastatin 8 (TRPM8) is a member of the TRP family, and is activated at temperatures below 22°C, or by cooling compounds such as menthol. In this study, it was found that a new role of TRPM8 activation on prostaglandin E2 (PGE2), an inflammatory cytokine and dendritogenesis stimulator of normal human melanocytes. Normal human keratinocytes were pretreated with menthol or incubated at 22°C for TRPM8 activation before ultraviolet (UV)-B irradiation. To examine the specificity between TRPM8 activation and PGE2 release, we inhibited TRPM8 with the antagonist (capsazepine), or introduced TRPM8 siRNA for a gene silencing experiment. UV-B irradiation significantly induced PGE2 release in normal human keratinocytes. Interestingly, activation of TRPM8 at 22°C or with menthol inhibited UV-B-induced PGE2 release. The effect of the TRPM8 agonist was completely blocked by pretreatment with the TRPM8 antagonist, capsazepine. When TRPM8 expression was suppressed by siRNA, UV-B irradiation still upregulated PGE2 in keratinocytes, but pretreatment of menthol or low temperature did not inhibit UV-B-induced PGE2. In conclusion, the activation of TRPM8 inhibits UV-B-induced PGE2 production in keratinocytes, and the activation of TRPM8 may reduce inflammatory responses in skin. PMID:24580132

Park, Nok-Hyun; Na, Yong-Joo; Choi, Hyang-Tae; Cho, Jun-Cheol; Lee, Hae-Kwang

2013-11-01

153

Apoptosis signaling pathways and lymphocyte homeostasis  

Microsoft Academic Search

It has been almost three decades since the term “apoptosis” was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis

Guangwu Xu; Yufang Shi

2007-01-01

154

Apoptosis in Neural Development and Disease  

Microsoft Academic Search

Cell death via apoptosis is a prominent feature in mammalian neural development. Recent studies into the basic mechanism of apoptosis have revealed biochemical pathways that control and execute apoptosis in mammalian cells. Protein factors in these pathways play important roles during development in regulating the balance between neuronal life and death. Additionally, mounting evidence indicates such pathways may also be

Deepak Nijhawan; Narimon Honarpour; Xiaodong Wang

2000-01-01

155

Analysis of fumonisin B1-induced apoptosis.  

PubMed Central

Fumonisins are mycotoxins produced by Fusarium moniliforme, a prevalent fungus that infects corn and other cereal grains. Fumonisin B1(FB1 is the most common mycotoxin produced by F. moniliforme, suggesting it has toxicologic significance. The structure of FB1 resembles sphingoid bases, and it inhibits ceramide synthase. Because sphingoid bases regulate cell growth, differentiation, transformation, and apoptosis, it is not surprising to find that FB1 can alter growth of certain mammalian cells. Previous studies concluded FB1-induced apoptosis, or cell cycle arrest, in African green monkey kidney fibroblasts (CV-1). In this study we have identified genes that inhibit FB1 induced apoptosis in CV-1 cells and two mouse embryo fibroblasts (MEF). A baculovirus gene, inhibitor of apoptosis (CpIAP), protected these cells from apoptosis. CpIAP blocks apoptosis induced by the tumor necrosis factor (TNF) pathway as well as other mechanisms. Further support for the involvement of the TNF signal transduction pathway in FB1 induced apoptosis was the cleavage of caspase 8. Inhibition of caspases by the baculovirus gene (italic)p35 also inhibited FB1-induced apoptosis. The tumor suppressor gene p53 was not required for FB1 induced apoptosis because p53-/- MEF undergo apoptosis following FB1 treatment. Furthermore, Bcl-2 was not an effective inhibitor of FB1-induced apoptosis in CV-1 cells or p53+/+ MEF. In summary, these results provide new information to help understand the mechanism by which FB1 induces apoptosis. PMID:11359701

Jones, C; Ciacci-Zanella, J R; Zhang, Y; Henderson, G; Dickman, M

2001-01-01

156

uPAR and Cathepsin B Downregulation Induces Apoptosis by Targeting Calcineurin A to BAD via Bcl-2 in Glioma  

PubMed Central

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3?, and increased the interaction of BAD with Bcl-Xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD and caspase 3 as well as PARP activation, cytochrome c and SMAC release. These effects were inhibited by FK506 (10 ?M), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 ?g/mL). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma. PMID:21964739

Malla, Rama Rao; Gopinath, Sreelatha; Gondi, Christopher S.; Alapati, Kiranmai; Dinh, Dzung H.; Tsung, Andrew J.; Rao, Jasti S.

2011-01-01

157

Simultaneous determination of most prescribed antibiotics in multiple urban wastewater by SPE-LC-MS/MS.  

PubMed

A rapid analytical method was developed for the application of a long-term monitoring (>one year) of the most prescribed and often in hospitals used antibiotics in diverse wastewaters of an urban sewage treatment plant (STP). Additionally to the selected multi-class antibiotics amoxicillin, penicillin V and piperacillin (penicillins), cefotaxime and cefuroxime (cephalosporins), azithromycin, clarithromycin and roxithromycin (macrolids), ciprofloxacin and levofloxacin-ofloxacin (fluoroquinolones), clindamycin (lincosamide), doxycycline (tetracycline), sulfamethoxazole (sulfonamide) and trimethoprim (dihydrofolate reductase inhibitor), the bioactive metabolite clindamycin-sulfoxide, the reserve antibiotic vancomycin (glycopeptide) and as tracer of the STP the anticonvulsant carbamazepine and the antifungal fluconazole were involved. The analytical method combines a low-sample-volume solid phase extraction (SPE), followed by a chromatographic separation using a reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC) technique, respectively, coupled to a triple quadrupole mass spectrometer. Detection was performed with multiple reaction monitoring (MRM) measured with positive electrospray ionization (ESI+). The extraction efficiency of different SPE cartridges and optimized pH-values of the preparation procedure were tested. Finally, the extraction of antibiotics was realized with the Oasis HLB cartridge and a pH adjustment at 3.5. An external calibration curve in diluted blank urine was used for quality control of the sample set of daily composite samples of the STP for the duration of one year monitoring. The squared coefficient of determination (r(2)) in the concentration range (20-20,000ng/L or 100-100,000ng/L) of the calibration curves for the method was higher than 0.99 for all determined substances. The limit of quantification (LoQ) ranged between 0.8ng/L (azithromycin) and 245.1ng/L (vancomycin). Furthermore, a standard addition was used for quantification in wastewater samples. The process efficiencies ranged from 20% (doxycycline) to 134% (cefuroxime) in influent samples and from 31% (doxycycline) to 171% (cefuroxime) in effluent samples of the STP. All selected substances have been found in wastewater samples. Cefuroxime, doxycycline, levofloxacin, piperacillin, sulfamethoxazole and carbamazepine showed highest concentrations up to 6.2?g/L. PMID:25171505

Rossmann, Julia; Schubert, Sara; Gurke, Robert; Oertel, Reinhard; Kirch, Wilhelm

2014-10-15

158

Apoptosis in rotator cuff tendonopathy  

Microsoft Academic Search

The aim of this study was to investigate the involvement of apoptosis (programmed cell death) in the pathogenesis of rotator cuff disorders. The edges of torn supraspinatus rotator cuff tendons were collected from patients with rotator cuff tear (n=25). Samples of the intra-articular portion of subscapularis tendons were collected from patients without rotator cuff tear as control (n=6). To minimize

Jun Yuan; George A. C. Murrell; Ai-Qun Wei; Min-Xia Wang

2002-01-01

159

Mitochondrial Control of Nuclear Apoptosis  

Microsoft Academic Search

Summary Anucleate cells can be induced to undergo programmed cell death (PCD), indicating the exist- ence of a cytoplasmic PCD pathway that functions independently from the nucleus. Cytoplas- mic structures including mitochondria have been shown to participate in the control of apop- totic nuclear disintegration. Before cells exhibit common signs of nuclear apoptosis (chromatin condensation and endonuclease-mediated DNA fragmentation), they

Naoufal Zamzami; Santos A. Susin; Philippe Marchetti

1996-01-01

160

CORRTEX Diagnostic Deployment for the SPE-III experiment, 24 July 2012: Fielding Report and Preliminary Data Analysis  

SciTech Connect

The Continuous Reflectometry for Radius vs Time Experiments (CORRTEX) diagnostic system was deployed for the third explosives test in the Source Physics Experiment (SPE) sequence to monitor and verify several conditions of the experiment including the detonation velocity of the explosive package and functioning of explosive initiators. Six distance-marked coaxial cables were installed on the SPE-III explosives canister, and key locations documented through along-cable length measurements and photography. CORRTEX uses electrical-pulse time-domain reflectometry to continuously record the two-way transit time (TWTT) of the cables. As the shock front of the detonation advances, the coaxial cable is shorted or destroyed, and the resulting TWTT also decreases. Interpretation of these changes as a function of TWTT can be converted to positional measurements using known parameters of the cables.

Sandoval, Thomas D. [Los Alamos National Laboratory; Schultz-Fellenz, Emily S. [Los Alamos National Laboratory

2012-08-29

161

Screening organic micropollutants in surface waters by SPE extraction and ecotoxicological testing.  

PubMed

Complex mixtures of toxic substances occurring in surface waters are difficult to characterise by chemical analyses because each compound occurs at a very low concentration and requires a specific analytical method to be identified. Ecotoxicological tests on water extracts can be used as a screening tool to evaluate quickly and simply the overall quality of a water body with regard to micropollutant contamination. In this work, a pre-concentration procedure based on solid-phase extraction (SPE), suitable for both biological testing and analytical determination, is proposed. The extraction procedure is an improved version of a methodology used to evaluate the toxicity of organic micropollutants occurring in surface waters. It offers the advantage of using disposable commercial cartridges, which are easier to manage than the columns prepared with macromolecular resins. Water extracts from two representative Italian rivers, characterised by a different gradient of potential contamination and prepared according to the new concentration techniques, are used. The acute toxicity of the water extracts is tested on Daphnia magna and the bioluminescence inhibition in Vibrio fischeri. Criteria based on the concentration factor (CF) are proposed for assessing the hazard to aquatic life due to the exposure to toxic substances in surface waters. The aim of hazard ranking is to focus analytical efforts towards those samples that show the highest toxic potential. PMID:14675841

Galassi, Silvana; Guzzella, Licia; Croce, Valeria

2004-03-01

162

SPE speciation of inorganic arsenic in rice followed by hydride-generation atomic fluorescence spectrometric quantification.  

PubMed

Due to high toxicity, inorganic arsenic (iAs) species are the focus of monitoring effort worldwide. In this work arsenic was first extracted from rice by microwave-assisted digestion in HNO3-H2O2, during which As(III) was oxidized to As(V). Silica-based strong anion exchange cartridges were used to separate As(V) from organic forms. After prereduction by iodide, iAs was quantified by hydride-generation atomic fluorescence spectrometry (HG-AFS). This method achieved 1.3 ng g(-1) limit of detection (LOD), and 94 ± 3% and 93 ± 5% recoveries, respectively, for As(III) and As(V) at 100 ng g(-1). Validation was performed using standard reference material NIST 1568a (102 ng g(-1)) and ERM BC211 (124 ng g(-1)) rice flour. By eliminating chromatography, SPE speciation gained throughput and cost advantages. HG-AFS, at 10% budget and operation cost of a typical inductively-couple plasma mass spectrometer (ICPMS), proved highly sensitive and specific for iAs quantification. PMID:24401405

Chen, Guoying; Chen, Tuanwei

2014-02-01

163

SPE/WPC reserve definitions to provide more accurate, consistent estimates  

SciTech Connect

Oil and gas reserves make up a producing company`s asset base, which generates future profits and investment capital. Hydrocarbon reserves are also a major source of energy for international governments, in addition to being an important aspect of a country`s stability both economically and politically. Therefore, both industry and governments must know the amount of oil and gas currently available for production, as well as the available quantities that are expected in the future through field development, technological advances and exploration activities. For this purpose, an industry-wide nomenclature is required to classify the current and future quantities predicted to be recovered from hydrocarbon bearing reservoirs based on the likelihood of their commercial recoverability. A single set of reserve definitions jointly drafted by SPE and WPC was approved in March 1997. The result of several years of collaboration between the two groups, the single definition set, which provides a standard nomenclature, should increase accuracy in reserves evaluation and ensure consistency in reserves classification throughout the industry.

NONE

1997-09-01

164

Characterisation of Antimicrobial Extracts from Dandelion Root (Taraxacum officinale) Using LC-SPE-NMR.  

PubMed

Plant extracts have traditionally been used as sources of natural antimicrobial compounds, although in many cases, the compounds responsible for their antimicrobial efficacy have not been identified. In this study, crude and dialysed extracts from dandelion root (Taraxacum officinale) were evaluated for their antimicrobial properties against Gram positive and Gram negative bacterial strains. The methanol hydrophobic crude extract (DRE3) demonstrated the strongest inhibition of microbial growth against Staphylococcus aureus, methicillin-resistant S. aureus and Bacillus cereus strains. Normal phase (NP) fractionation of DRE3 resulted in two fractions (NPF4 and NPF5) with enhanced antimicrobial activity. Further NP fractionation of NPF4 resulted in two fractions (NPF403 and NPF406) with increased antimicrobial activity. Further isolation and characterisation of compounds in NPF406 using liquid chromatography solid phase extraction nuclear magnetic resonance LC-SPE-NMR resulted in the identification of 9-hydroxyoctadecatrienoic acid and 9-hydroxyoctadecadienoic acid, while the phenolic compounds vanillin, coniferaldehyde and p-methoxyphenylglyoxylic acid were also identified respectively. The molecular mass of these compounds was confirmed by LC mass spectroscopy (MS)/MS. In summary, the antimicrobial efficacy of dandelion root extracts demonstrated in this study support the use of dandelion root as a source of natural antimicrobial compounds. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25644491

Kenny, O; Brunton, N P; Walsh, D; Hewage, C M; McLoughlin, P; Smyth, T J

2015-04-01

165

Data Release Report for Source Physics Experiment 1 (SPE-1), Nevada National Security Site  

SciTech Connect

The first Source Physics Experiment shot (SPE-1) was conducted in May 2011. The explosive source was a ~100-kilogram TNT-equivalent chemical set at a depth of 60 meters. It was recorded by an extensive set of instrumentation that includes sensors both at near-field (less than 100 meters) and far-field (more than 100 meters) distances. The near-field instruments consisted of three-component accelerometers deployed in boreholes around the shot and a set of singlecomponent vertical accelerometers on the surface. The far-field network comprised a variety of seismic and acoustic sensors, including short-period geophones, broadband seismometers, three-component accelerometers, and rotational seismometers at distances of 100 meters to 25 kilometers. This report coincides with the release of these data for analysts and organizations that are not participants in this program. This report describes the first Source Physics Experiment and the various types of near-field and far-field data that are available.

Townsend, Margaret [NSTec] [NSTec; Mercadente, Jennifer [NSTec] [NSTec

2014-04-28

166

Apoptosis in virus infection dynamics models  

PubMed Central

In this paper, on the basis of the simplified two-dimensional virus infection dynamics model, we propose two extended models that aim at incorporating the influence of activation-induced apoptosis which directly affects the population of uninfected cells. The theoretical analysis shows that increasing apoptosis plays a positive role in control of virus infection. However, after being included the third population of cytotoxic T lymphocytes immune response in HIV-infected patients, it shows that depending on intensity of the apoptosis of healthy cells, the apoptosis can either promote or comfort the long-term evolution of HIV infection. Further, the discrete-time delay of apoptosis is incorporated into the pervious model. Stability switching occurs as the time delay in apoptosis increases. Numerical simulations are performed to illustrate the theoretical results and display the different impacts of a delay in apoptosis. PMID:24963975

Fan, Ruili; Dong, Yueping; Huang, Gang; Takeuchi, Yasuhiro

2014-01-01

167

Apoptosis in virus infection dynamics models.  

PubMed

In this paper, on the basis of the simplified two-dimensional virus infection dynamics model, we propose two extended models that aim at incorporating the influence of activation-induced apoptosis which directly affects the population of uninfected cells. The theoretical analysis shows that increasing apoptosis plays a positive role in control of virus infection. However, after being included the third population of cytotoxic T lymphocytes immune response in HIV-infected patients, it shows that depending on intensity of the apoptosis of healthy cells, the apoptosis can either promote or comfort the long-term evolution of HIV infection. Further, the discrete-time delay of apoptosis is incorporated into the pervious model. Stability switching occurs as the time delay in apoptosis increases. Numerical simulations are performed to illustrate the theoretical results and display the different impacts of a delay in apoptosis. PMID:24963975

Fan, Ruili; Dong, Yueping; Huang, Gang; Takeuchi, Yasuhiro

2014-01-01

168

Ion channels in the regulation of apoptosis.  

PubMed

Apoptosis, a type of genetically controlled cell death, is a fundamental cellular mechanism utilized by multicellular organisms for disposal of cells that are no longer needed or potentially detrimental. Given the crucial role of apoptosis in physiology, deregulation of apoptotic machinery is associated with various diseases as well as abnormalities in development. Acquired resistance to apoptosis represents the common feature of most and perhaps all types of cancer. Therefore, repairing and reactivating apoptosis represents a promising strategy to fight cancer. Accumulated evidence identifies ion channels as essential regulators of apoptosis. However, the contribution of specific ion channels to apoptosis varies greatly depending on cell type, ion channel type and intracellular localization, pathology as well as intracellular signaling pathways involved. Here we discuss the involvement of major types of ion channels in apoptosis regulation. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. PMID:25450339

Kondratskyi, Artem; Kondratska, Kateryna; Skryma, Roman; Prevarskaya, Natalia

2014-10-27

169

The Domains of Apoptosis: A Genomics Perspective  

NSDL National Science Digital Library

Programmed cell death, also known as apoptosis, plays important roles in many aspects of normal physiology in animal species, including programmed death associated with fetal development or metamorphosis, tissue homeostasis, elimination of inappropriate cells in the immune system, and some aspects of aging. Defects in the regulation of apoptosis contribute to multiple diseases; for example, lack of apoptosis contributes to cancer, and excessive apoptosis is associated with neurodegenerative and autoimmune diseases. Apoptosis also functions as a defense mechanism against viruses and microbes. In the regulatory machinery that contols apoptosis, interactions between key proteins are determined by small protein segments or domains that allow cells to react appropriately to signals from within or outside the cell. In this Review, we examine the range of human proteins that contain these domains and discuss how the resultant protein interactions help control cell death. These same domains provide possible targets for the development of drugs that could beneficially modulate apoptosis.

John C. Reed (The Burnham Institute; REV)

2004-06-29

170

GSK3? signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells  

PubMed Central

Ultraviolet B (UVB) exposure causes damage to skin and represents the primary etiological agent for skin cancer formation. UVB induces DNA damage and apoptosis in epidermal cells. In this study, we demonstrated that UVB activated autophagy in JB6 epidermal cells, which was evident by the formation of LC3 puncta, the induction of LC3 lipidation, the increase in beclin 1 expression, and the decrease in the levels of p62. Autophagy appeared to be a protective response to UVB-induced damage because inhibition of autophagy exacerbated UVB-induced cell death, and stimulation of autophagy offered protection. Furthermore, we demonstrated that glycogen synthase kinase 3? (GSK3?) was involved in UVB-induced autophagy. UVB inhibited GSK3? activation by simultaneously enhancing phosphorylation at Ser9 and suppressing Tyr216 phosphorylation. GSK3? negatively regulated autophagy; overexpression of wild-type or S9A (constitutive-active) GSK3? mutant inhibited UVB-mediated autophagy, while overexpression of a dominant-negative K85R mutant enhanced UVB-mediated autophagy. Inhibition of GSK3? also offered protection against UVB-mediated damage. UVB activated AMP-activated protein kinase (AMPK), an important regulator of autophagy through the inhibition of GSK3?. Taken together, our results suggest that UVB-stimulated autophagy is a protective response for epidermal cells and is mediated by the GSK3?/AMPK pathway. PMID:22961228

YANG, YANG; WANG, HAIPING; WANG, SIYING; XU, MEI; LIU, MEI; LIAO, MINGJUN; FRANK, JACQUELINE A.; ADHIKARI, SABAL; BOWER, KIMBERLY A.; SHI, XIANGLIN; MA, CUILING; LUO, JIA

2012-01-01

171

GSK3? signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells.  

PubMed

Ultraviolet B (UVB) exposure causes damage to skin and represents the primary etiological agent for skin cancer formation. UVB induces DNA damage and apoptosis in epidermal cells. In this study, we demonstrated that UVB activated autophagy in JB6 epidermal cells, which was evident by the formation of LC3 puncta, the induction of LC3 lipidation, the increase in beclin 1 expression, and the decrease in the levels of p62. Autophagy appeared to be a protective response to UVB-induced damage because inhibition of autophagy exacerbated UVB-induced cell death, and stimulation of autophagy offered protection. Furthermore, we demonstrated that glycogen synthase kinase 3? (GSK3?) was involved in UVB-induced autophagy. UVB inhibited GSK3? activation by simultaneously enhancing phosphorylation at Ser9 and suppressing Tyr216 phosphorylation. GSK3? negatively regulated autophagy; overexpression of wild?type or S9A (constitutive-active) GSK3? mutant inhibited UVB-mediated autophagy, while overexpression of a dominant-negative K85R mutant enhanced UVB-mediated autophagy. Inhibition of GSK3? also offered protection against UVB-mediated damage. UVB activated AMP-activated protein kinase (AMPK), an important regulator of autophagy through the inhibition of GSK3?. Taken together, our results suggest that UVB-stimulated autophagy is a protective response for epidermal cells and is mediated by the GSK3?/AMPK pathway. PMID:22961228

Yang, Yang; Wang, Haiping; Wang, Siying; Xu, Mei; Liu, Mei; Liao, Mingjun; Frank, Jacqueline A; Adhikari, Sabal; Bower, Kimberly A; Shi, Xianglin; Ma, Cuiling; Luo, Jia

2012-11-01

172

Analysis of drugs of abuse by online SPE-LC high resolution mass spectrometry: Communal assessment of consumption.  

PubMed

An online SPE-LC-HRMS method was developed to monitor the consumption of 18 drugs of abuse (DOAs) including amphetamines, opioids, cocainics, cannabinoids, lysergics, and their corresponding metabolites in a well characterized college campus setting via wastewater analysis. Filtered and diluted (10×) sewage water samples (5mL inj.) were automatically pre-concentrated and analyzed in 15min using a Thermo EQuan MAX online SPE system equipped with a HyperSep™ Retain PEP (20×2.1mm×12?m) SPE column and a Hypersil Gold™ aQ (150×2.1mm×3?m) analytical column. A Q Exactive™ Hybrid Quadrupole-Orbitrap HRMS was used in full scan mode (R=140,000) for positive identification, and quantitation of target compounds. Method detection limits for all analytes ranged between 0.6 and 1.7ng/L in sewage. A total of 14 DOAs were detected from two different locations (dorms and main college campus) within a one-year period. Most frequently detected drugs throughout the entire study were amphetamine (>96%) and THC's metabolite 11-nor-9-carboxy-?-9-THC (>100%) with maximum concentrations of 5956 and 2413ng/L respectively. Daily doses per 1000 people were determined in order to assess consumption of THC, amphetamine, heroin and cocaine, in both dorms and main campus. PMID:25553546

Heuett, Nubia V; Ramirez, Cesar E; Fernandez, Adolfo; Gardinali, Piero R

2015-04-01

173

Solid-phase extraction and purification of membrane proteins using a UV-modified PMMA microfluidic bioaffinity ?SPE device.  

PubMed

We present a novel microfluidic solid-phase extraction (?SPE) device for the affinity enrichment of biotinylated membrane proteins from whole cell lysates. The device offers features that address challenges currently associated with the extraction and purification of membrane proteins from whole cell lysates, including the ability to release the enriched membrane protein fraction from the extraction surface so that they are available for downstream processing. The extraction bed was fabricated in PMMA using hot embossing and was comprised of 3600 micropillars. Activation of the PMMA micropillars by UV/O3 treatment permitted generation of surface-confined carboxylic acid groups and the covalent attachment of NeutrAvidin onto the ?SPE device surfaces, which was used to affinity select biotinylated MCF-7 membrane proteins directly from whole cell lysates. The inclusion of a disulfide linker within the biotin moiety permitted release of the isolated membrane proteins via DTT incubation. Very low levels (?20 fmol) of membrane proteins could be isolated and recovered with ?89% efficiency with a bed capacity of 1.7 pmol. Western blotting indicated no traces of cytosolic proteins in the membrane protein fraction as compared to significant contamination using a commercial detergent-based method. We highlight future avenues for enhanced extraction efficiency and increased dynamic range of the ?SPE device using computational simulations of different micropillar geometries to guide future device designs. PMID:24487280

Battle, Katrina N; Jackson, Joshua M; Witek, Ma?gorzata A; Hupert, Mateusz L; Hunsucker, Sally A; Armistead, Paul M; Soper, Steven A

2014-03-21

174

Solid-phase Extraction and Purification of Membrane Proteins Using a UV-modified PMMA Microfluidic Bioaffinity ?SPE Device  

PubMed Central

We present a novel microfluidic solid-phase extraction (?SPE) device for the affinity enrichment of biotinylated membrane proteins from whole cell lysates. The device offers features that address challenges currently associated with the extraction and purification of membrane proteins from whole cell lysates, including the ability to release the enriched membrane protein fraction from the extraction surface so that they are available for downstream processing. The extraction bed was fabricated in PMMA using hot embossing and was comprised of 3,600 micropillars. Activation of the PMMA micropillars by UV/O3 treatment permitted generation of surface-confined carboxylic acid groups and the covalent attachment of NeutrAvidin onto the ?SPE device surfaces, which was used to affinity select biotinylated MCF-7 membrane proteins directly from whole cell lysates. The inclusion of a disulfide linker within the biotin moiety permitted release of the isolated membrane proteins via DTT incubation. Very low levels (~20 fmol) of membrane proteins could be isolated and recovered with ~89% efficiency with a bed capacity of 1.7 pmol. Western blotting indicated no traces of cytosolic proteins in the membrane protein fraction as compared to significant contamination using a commercial detergent-based method. We highlight future avenues for enhanced extraction efficiency and increased dynamic range of the ?SPE device using computational simulations of different micropillar geometries to guide future device designs. PMID:24487280

Battle, Katrina N.; Jackson, Joshua M.; Witek, Ma?gorzata A.; Hupert, Mateusz L.; Hunsucker, Sally A.; Armistead, Paul M.; Soper, Steven A.

2014-01-01

175

Colorimetric-Solid Phase Extraction Technology for Water Quality Monitoring: Evaluation of C-SPE and Debubbling Methods in Microgravity  

NASA Technical Reports Server (NTRS)

Colorimetric-solid phase extraction (C-SPE) is being developed as a method for in-flight monitoring of spacecraft water quality. C-SPE is based on measuring the change in the diffuse reflectance spectrum of indicator disks following exposure to a water sample. Previous microgravity testing has shown that air bubbles suspended in water samples can cause uncertainty in the volume of liquid passed through the disks, leading to errors in the determination of water quality parameter concentrations. We report here the results of a recent series of C-9 microgravity experiments designed to evaluate manual manipulation as a means to collect bubble-free water samples of specified volumes from water sample bags containing up to 47% air. The effectiveness of manual manipulation was verified by comparing the results from C-SPE analyses of silver(I) and iodine performed in-flight using samples collected and debubbled in microgravity to those performed on-ground using bubble-free samples. The ground and flight results showed excellent agreement, demonstrating that manual manipulation is an effective means for collecting bubble-free water samples in microgravity.

Hazen-Bosveld, April; Lipert, Robert J.; Nordling, John; Shih, Chien-Ju; Siperko, Lorraine; Porter, Marc D.; Gazda, Daniel B.; Rutz, Jeff A.; Straub, John E.; Schultz, John R.; McCoy, J. Torin

2007-01-01

176

D Model Simulations of Long-Term Changes in Chemical Composition of the Middle Atmosphere after Spe of October 2003  

NASA Astrophysics Data System (ADS)

Energetic particles (EPs): solar and galactic cosmic rays, and precipitating electrons, which penetrate into the atmosphere of the Earth at high latitudes, cause its ionization and transform chemical composition including ozone. Ozone response, which is caused by additional production of nitrogen and hydrogen oxides in the middle atmosphere, depends of magnitudes of particle fluxes and its energetic spectrum. During the deceleration in the atmosphere each pair of produced ions born 1.25 molecular of NO and 2.0 molecular of OH (Porter et al, 1976; Solomon and Crutzen, 1981), which destroy ozone in chemical catalytic cycles. Increase of hydrogen compounds leads usually to short term effects in the atmosphere, and NOx production by energetic particles induces long-term consequences. This conception was used in order to investigate long-term response of ozone and other species to major SPE of October 2003 using 3D transport-photochemical model (Krivolutsky et al., 2006). Daily averaged temperature and wind global fields used in simulations have been calculated with middle atmosphere GCM. The results of 3D simulations showed that this major SPE caused strong depletion in ozone during several days, which was switched out after sunset. At the same time the effect in ozone appears again after sunrise due to accumulated NOy. Comparison with observations is discussed. Simulated changes in composition over South polar region after SPE differ from the response over Northern polar region.

Krivolutsky, Alexei A.; Krivolutsky, Alexei A.; Vyushkova, Tatyana; Kuminov, Alexander

177

Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS.  

PubMed

The newly established hyphenated instrumentation of LC/DAD/SPE/NMR and LC/UV/(ESI)MS techniques have been applied for separation and structure verification of the major known constituents present in Greek Hypericum perforatum extracts. The chromatographic separation was performed on a C18 column. Acetonitrile-water was used as a mobile phase. For the on-line NMR detection, the analytes eluted from column were trapped one by one onto separate SPE cartridges, and hereafter transported into the NMR flow-cell. LC/DAD/SPE/NMR and LC/UV/MS allowed the characterization of constituents of Greek H. perforatum, mainly naphtodianthrones (hypericin, pseudohypericin, protohypericin, protopseudohypericin), phloroglucinols (hyperforin, adhyperforin), flavonoids (quercetin, quercitrin, isoquercitrin, hyperoside, astilbin, miquelianin, I3,II8-biapigenin) and phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid). Two phloroglucinols (hyperfirin and adhyperfirin) were detected for the first time, which have been previously reported to be precursors in the biosynthesis of hyperforin and adhyperforin. PMID:17196625

Tatsis, Evangelos C; Boeren, Sjef; Exarchou, Vassiliki; Troganis, Anastassios N; Vervoort, Jacques; Gerothanassis, Ioannis P

2007-02-01

178

Pin1 in Neuronal Apoptosis  

PubMed Central

While the role of the prolyl isomerase Pin1 in dividing cells has long been recognized, Pin1’s function in postmitotic neurons is poorly understood. We have identified a novel mechanism by which Pin1 mediates activation of the mitochondrial cell death machinery specifically in neurons. This perspective presents a sophisticated signaling pathway that triggers neuronal apoptosis upon JNK-mediated phosphorylation of the BH3-only protein BIMEL at serine 65. Pin1 is enriched at the mitochondria in neurons together with BIMEL and components of a neuron-specific JNK signaling complex and functions as a molecular switch that couples the phosphorylation of BIMEL by JNK to apoptosis specifically in neurons. We discuss how these findings relate to our understanding of the development of the nervous system and the pathogenesis of neurologic disorders. PMID:17568190

Becker, Esther B.E.; Bonni, Azad

2009-01-01

179

miR-125b induces cellular senescence in malignant melanoma  

PubMed Central

Background Micro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory. Methods We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and ?-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization. Results In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours. Conclusions Our results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma. PMID:24762088

2014-01-01

180

Survivin Inhibits Apoptosis in Cytotrophoblasts  

Microsoft Academic Search

Survivin, a protein that inhibits apoptosis, is expressed in a variety of tumour cells. We detected survivin-specific mRNA and protein in normal placental tissues, two human choriocarcinoma cell lines (JEG-3 and BeWo), and a trophoblastic cell line (tPA30-1) by reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and Western blotting. Immunohistochemically, survivin was localized to normal villous cytotrophoblasts, normal extravillous trophoblasts,

A. Shiozaki; K. Kataoka; M. Fujimura; H. Yuki; M. Sakai; S. Saito

2003-01-01

181

APOPTOSIS: Life and Death Decisions  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Screening small molecules for their ability to perturb a cellular pathway, a strategy called forward chemical genetics, can yield unexpected information about other pathway components. This is well illustrated by new work (Jiang et al.), as Nicholson and Thornberry discuss in their Perspective. Discovery of a small-molecule activator of apoptosis implicated a tumor suppressor protein and an oncoprotein in the regulation of the mitochondrial cell death pathway.

Donald W. Nicholson (Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories; )

2003-01-10

182

DNA Damage Response and Apoptosis  

PubMed Central

A number of methods have been developed to examine the morphologic, biochemical, and molecular changes that happen during the DNA damage response that may ultimately lead to death of cells through various mechanisms that include apoptosis. When cells are exposed to ionizing radiation or chemical DNA-damaging agents, double-stranded DNA breaks (DSB) are generated that rapidly result in the phosphorylation of histone variant H2AX. Because phosphorylation of H2AX at Ser 139 correlates well with each DSB, phospho-H2AX is a sensitive marker to used to examine the DNA damage and its repair. Apoptotic cells are characterized on the basis of their reduced DNA content and morphologic changes, including nuclear condensation, which can be detected by flow cytometry (sub-G1 DNA content), trypan blue, or Hoechst staining. The appearance of phosphatidylserine on the plasma membrane with annexin V–fluorochrome conjugates indicates the changes in plasma membrane composition and function. By combining it with propidium iodide staining, this method can also be used to distinguish early versus late apoptotic or necrotic events. The activation of caspases is another well-known biochemical marker of apoptosis. Finally, the Bcl-2 family of proteins and the mitochondria that play a critical role in DNA damage-induced apoptosis can be examined by translocation of Bax and cytochrome c in and out of mitochondria. In this chapter, we discuss the most commonly used techniques used in our laboratory for determining the DNA damage response leading to apoptosis. PMID:18603118

Plesca, Dragos; Mazumder, Suparna; Almasan, Alexandru

2010-01-01

183

TGF-?1 Suppresses T Cell Infiltration and VP2 Puff B Mutation Enhances Apoptosis in Acute Polioencephalitis Induced by Theiler’s Virus  

PubMed Central

GDVII and DA strains of Theiler’s murine encephalomyelitis virus (TMEV) differ in VP2 puff B. One week after GDVII virus infection, SJL/J mice had large numbers of TUNEL+ apoptotic cells with a relative lack of T cell infiltration in the brain. DA viruses with mutation in puff B induced higher levels of apoptosis than wild-type DA virus, but levels of inflammation in brains were similar between DA and DA virus mutants. The difference in inflammation among TMEVs could be due to TGF-?1 expression that was seen only in GDVII virus infection and negatively correlated with CD3+ T cell infiltration. PMID:17804084

Tsunoda, Ikuo; Libbey, Jane E.; Fujinami, Robert S.

2007-01-01

184

Geologic Assessment of the Damage Zone from the Second Test at Source Physics Experiment-Nevada (SPE-N)  

SciTech Connect

The National Center for Nuclear Security (NCNS), established by the U.S. Department of Energy, National Nuclear Security Administration, is conducting a series of explosive tests at the Nevada National Security Site (NNSS; formerly the Nevada Test Site) that are designed to increase the understanding of certain basic physical phenomena associated with underground explosions. These tests will aid in developing technologies that might be used to detect underground nuclear explosions in support of verification activities for the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The initial NCNS project is a series of explosive tests, known collectively as the Source Physics Experiment at the NNSS (SPE-N), being conducted in granitic rocks at the Climax stock in northern Yucca Flat. The SPE-N test series is designed to study the generation and propagation of seismic waves. The data will be used to improve the predictive capability of calculational models for detecting and characterizing underground explosions. The first SPE-N test (SPE-N-1) was a “calibration” shot conducted in May 2011, using 100 kilograms (kg) of explosives at the depth of 54.9 meters (m) (180 feet [ft]) in the U-15n source hole. SPE-N-2 was conducted in October 2011, using 1,000 kg of explosives at the depth of 45.7 m (150 ft) in the same source hole. Following the SPE-N-2 test, the core hole U-15n#10 was drilled at an angle from the surface to intercept the SPE-N-2 shot point location to obtain information necessary to characterize the damage zone. The desire was to determine the position of the damage zone near the shot point, at least on the northeast side, where the core hole penetrated it. The three-dimensional shape and symmetry of the damage zone are unknown at this time. Rather than spherical in shape, the dimensions of the damage zone could be influenced by the natural fracture sets in the vicinity. Geologic characterization of the borehole included geophysical logging, a directional survey, and geologic description of the core to document visual evidence of damage. Selected core samples were provided to Sandia National Laboratories (SNL) for laboratory tests (to be reported by SNL). A significant natural fault zone was encountered in the U-15n#10 angle core hole between the drilled depths of 149 and 155 ft (straight-line distance or range station [RS] from the shot point of 7.5 to 5.7 m). However, several of the fractures observed in the U-15n#10 hole are interpreted as having been caused by the explosion. These fractures are characterized by a “fresh,” mechanically broken look, with uncoated and very irregular surfaces. They tend to terminate against natural fractures and have orientations that differ from the previously defined natural fracture sets. The most distant fracture from the shot point that could be interpreted as having been caused by the explosion was seen at approximately RS 10.0 m. No other possibly explosion-induced fractures are apparent above the fault, but are common starting at RS 5.4 m, which is below the fault. It is unknown how the fault zone might have affected the propagation of seismic waves or how the materials in the fault zone (altered granite, breccia, gouge) were affected by the explosion. From RS 3.3 m to the end of the recovered core at RS 1.6 m, some of the core samples are softer and lighter in color, but do not appear to be weathered. It is thought this could be indicative of the presence of distributed microfracturing.

,

2012-09-18

185

Human papillomavirus oncoproteins and apoptosis (Review).  

PubMed

The aim of this study was to review the literature and identify the association between human papillomavirus (HPV) oncoproteins and apoptosis. HPV-associated apoptosis may be primarily blocked by a number of oncoproteins, including E5, E6 and E7. E5 protein protects cells from tumor necrosis factor-associated apoptosis; the oncoprotein E6 predominantly inhibits apoptosis through the p53 pathway; and oncoprotein E7 is involved in apoptosis activation and inhibition. In addition, HPV oncoproteins are involved in activating or repressing the transcription of E6/E7. In conclusion, HPV oncoproteins, including E5, E6 and E7 protein, may interfere with apoptosis via certain regulatory principles. PMID:24348754

Jiang, Peiyue; Yue, Ying

2014-01-01

186

Local Anesthetics Induce Human Renal Cell Apoptosis  

Microsoft Academic Search

Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end

H. Thomas Lee; Hua Xu; Cory D. Siegel; Igor E. Krichevsky

2003-01-01

187

Apoptosis and aging: increased resistance to apoptosis enhances the aging process  

Microsoft Academic Search

Apoptosis is a vital component in the evolutionarily conserved host defense system. Apoptosis is the guardian of tissue integrity\\u000a by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since\\u000a during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally\\u000a deficient, post-mitotic cells with

Antero Salminen; Johanna Ojala; Kai Kaarniranta

2011-01-01

188

Inhibitory Effects of Resveratrol on Melanin Synthesis in Ultraviolet B-Induced Pigmentation in Guinea Pig Skin  

PubMed Central

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits ?-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging. PMID:24596619

Lee, Taek Hwan; Seo, Jae Ok; Baek, So-Hyeon; Kim, Sun Yeou

2014-01-01

189

Effects of different light conditions on repair of UV-B-induced damage in carpospores of Chondrus ocellatus Holm  

NASA Astrophysics Data System (ADS)

We evaluated the effects of ultraviolet-B (UV-B) radiation and different light conditions on the repair of UV-B-induced damage in carpospores of Chondrus ocellatus Holm (Rhodophyta) in laboratory experiments. Carpospores were treated daily with different doses of UV-B radiation for 48 days, when vertical branches had formed in all treatments; after each daily treatment, the carpospores were subjected to photosynthetically active radiation (PAR), darkness, red light, or blue light during a 2-h repair stage. Carpospore diameters were measured every 4 days. We measured the growth and cellular contents of cyclobutane pyrimidine dimers (CPDs), chlorophyll a, phycoerythrin, and UV-B-absorbing mycosporine-like amino acids (MAAs) in carpospores on Day 48. Low doses of UV-B radiation (36 and 72 J/m2) accelerated the growth of C. ocellatus. However, as the amount of UV-B radiation increased, the growth rate decreased and morphological changes occurred. UV-B radiation significant damaged DNA and photosynthetic pigments and induced three kind of MAAs, palythine, asterina-330, and shinorine. PAR conditions were best for repairing UV-B-induced damage. Darkness promoted the activity of the DNA darkrepair mechanism. Red light enhanced phycoerythrin synthesis but inhibited light repair of DNA. Although blue light, increased the activity of DNA photolyase, greatly improving remediation efficiency, the growth and development of C. ocellatus carpospores were slower than in other light treatments.

Ju, Qing; Xiao, Hui; Wang, You; Tang, Xuexi

2015-03-01

190

Apoptosis and Molecular Targeting Therapy in Cancer  

PubMed Central

Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

2014-01-01

191

Death-Defining Immune Responses After Apoptosis  

PubMed Central

Apoptosis is a programmed form of cell death whereby characteristic internal cellular dismantling is accompanied by the preservation of plasma membrane integrity. Maintaining this order during apoptosis prevents the release of cellular contents and ensures a noninflammatory death. Here, we consider examples of apoptosis in different contexts and discuss how the same form of cell death could have different immunological consequences. Multiple parameters such as cell death as a result of microbial infection, the nature of the inflammatory microenvironment, the type of responding phagocytic cells and the genetic background of the host organism all differentially influence the immunological consequences of apoptosis. PMID:24903539

Campisi, L.; Cummings, R. J.; Blander, J. Magarian

2014-01-01

192

Targeting apoptosis pathways in childhood malignancies.  

PubMed

Evasion of apoptosis (programmed cell death) is a characteristic feature of human cancers including childhood malignancies. Since cytotoxic therapies such as chemotherapy or radiotherapy trigger apoptosis as a primary mechanism of action, resistance to apoptosis can also lead to treatment resistance. Studies on apoptosis pathways in childhood malignancies yielded a series of key molecules that can now be exploited as molecular targets for the development of targeted therapies. This strategy is anticipated to open novel perspectives for more effective treatment options for children with cancer. PMID:21036468

Fulda, Simone

2013-05-28

193

Photo-protective effect of americanin B against ultraviolet B-induced damage in cultured human keratinocytes.  

PubMed

Excessive ultraviolet (UV) radiation, a constituent of sunlight, can induce multiple types of skin damage. We recently demonstrated that americanin B, a lignin compound, protected cells against hydrogen peroxide (H2O2)-induced damage by exerting antioxidant effects and inhibiting apoptosis. In this study, we investigated the ability of americanin B to protect against cell injury induced by UVB (280-320nm), the most harmful UV wavelengths, in human HaCaT keratinocytes. Americanin B absorbed UVB, eliminated UVB-induced intracellular reactive oxygen species (ROS), and decreased the extent of UVB-induced oxidative modification of lipids, proteins, and DNA. In addition, americanin B inhibited UVB-induced apoptosis, as indicated by reductions in apoptotic body formation and DNA fragmentation. Furthermore, americanin B reversed the depolarization of the mitochondrial membrane induced by UVB exposure. These protective activities were associated with down-regulation of apoptosis-promoting proteins, Bax, caspase-9, and caspase-3 and up-regulation of an apoptosis inhibitor, Bcl-2. These results suggest that americanin B can protect human keratinocytes against UVB-induced cell damage. PMID:25461549

Zheng, Jian; Piao, Mei Jing; Kim, Ki Cheon; Yao, Cheng Wen; Cha, Ji Won; Shin, Jennifer H; Yoo, Suk Jae; Hyun, Jin Won

2014-11-01

194

Osteocyte Apoptosis Is Mechanically Regulated and Induces Angiogenesis In Vitro  

E-print Network

Osteocyte Apoptosis Is Mechanically Regulated and Induces Angiogenesis In Vitro Wing-Yee Cheung,1: Osteocyte apoptosis, associated with reduced interstitial fluid flow, precedes osteoclast precursor. Totestthe associationbetweenfluidflow andosteocyte apoptosis,osteocyte-like MLO-Y4 cellsweresubjectedto

You, Lidan

195

Simple SPE-HPLC determination of some common drugs and herbicides of environmental concern by pulsed amperometry.  

PubMed

In this work the electrochemical behavior of substances of environmental concern [bentazone, atrazine, carbamazepine, phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin, HPPH] on a glassy carbon working electrode (Ag/AgCl reference electrode) was studied with the aim to develop a HPLC method coupled with amperometric detection. Constant potential (DC), pulsed amperometric detection modes were studied. For the pulsed mode, several waveforms were set and investigated. Detection conditions were optimized as a function of eluent pH. In order to reduce the limits of detection and to analyze natural water samples, a SPE protocol was optimized to be coupled to the developed procedure. For this aim, five sorbents of different physico-chemical characteristics were tested optimizing a recovery procedure for each of the cartridge evaluated. At the optimized SPE conditions, recoveries were included in the range (R=90.2-100.5% for all the analytes, with excellent reproducibility (<%, n=3). The method detection limits obtained by pulsed amperometry after the SPE protocol (preconcentration factor 100) were 113 ng L(-1) (0.47 nmol L(-1)), 67 ng L(-1) (0.25 nmol L(-1)), 234 ng L(-1) (1.1 nmol L(-1)), for bentazone, HPPH and carbamazepine, respectively. Robustness of the method was assessed for each analyte at a concentration level corresponding to about three times the limit of detection, through the evaluation of intra-day (n=13) and inter-day tests (4 days, n=52). Finally the method was successfully applied for the analysis of a river sample (Po River, Turin, Italy). PMID:25281094

Rivoira, L; De Carlo, R M; Cavalli, S; Bruzzoniti, M C

2015-01-01

196

APOPTOSIS: Death by Crowd Control  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Cells often die by way of a controlled suicide called apoptosis. The proteins most responsible for the deed are caspases, specific proteases that are carefully regulated in the cell so that they only become activated when absolutely necessary. In his Perspective, Hengartner discusss results reported by Yang et al. in the same issue on how some of the central caspases responsible for cell death, such as CED-3, are activated by oligomerization, a process that is regulated by the anti-death protein CED-9, a member of the large Bcl-2 family.

Michael Hengartner (Cold Spring Harbor Laboratory; )

1998-08-28

197

Development of colorimetric solid Phase Extraction (C-SPE) for in-flight Monitoring of spacecraft Water Supplies  

SciTech Connect

Although having recently been extremely successful gathering data on the surface of Mars, robotic missions are not an effective substitute for the insight and knowledge about our solar system that can be gained though first-hand exploration. Earlier this year, President Bush presented a ''new course'' for the U.S. space program that shifts NASA's focus to the development of new manned space vehicles to the return of humans to the moon. Re-establishing the human presence on the moon will eventually lead to humans permanently living and working in space and also serve as a possible launch point for missions into deeper space. There are several obstacles to the realization of these goals, most notably the lack of life support and environmental regeneration and monitoring hardware capable of functioning on long duration spaceflight. In the case of the latter, past experience on the International Space Station (ISS), Mir, and the Space Shuttle has strongly underscored the need to develop broad spectrum in-flight chemical sensors that: (1) meet current environmental monitoring requirements on ISS as well as projected requirements for future missions, and (2) enable the in-situ acquisition and analysis of analytical data in order to further define on-orbit monitoring requirements. Additionally, systems must be designed to account for factors unique to on-orbit deployment such as crew time availability, payload restrictions, material consumption, and effective operation in microgravity. This dissertation focuses on the development, ground testing, and microgravity flight demonstration of Colorimetric Solid Phase Extraction (C-SPE) as a candidate technology to meet the near- and long-term water quality monitoring needs of NASA. The introduction will elaborate further on the operational and design requirements for on-orbit water quality monitoring systems by discussing some of the characteristics of an ''ideal'' system. A description of C-SPE and how the individual components of the platform are combined to satisfy many of these requirements is then presented, along with a literature review on the applications of C-SPE and similar sorption-spectrophotometric techniques. Finally, a brief overview of diffuse reflection spectroscopy and the Kubelka-Munk function, which are used to quantify analytes via C-SPE, is presented.

Daniel Bryan Gazda

2004-12-19

198

Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.  

PubMed

Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 ?mol/L concentration induced G0/G1 cell cycle arrest significantly (P < 0.05) and decreased the percentage of cells in the S and G2/M phase. Honokiol down-regulated the expression of cyclin D1, cyclin D2, Cdk2, Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis. PMID:21908486

Chilampalli, Chandeshwari; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Chandrasekher, Gudiseva; Fahmy, Hesham; Dwivedi, Chandradhar

2011-11-01

199

Broad-Spectrum Antibiotic or G-CSF as Potential Countermeasures for Impaired Control of Bacterial Infection Associated with an SPE Exposure during Spaceflight  

PubMed Central

A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body’s defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS) conditions and exposed to solar particle event (SPE)-like radiation. HS and SPE-like radiation treatment alone resulted in a borderline significant increase in morbidity. Therefore, development and testing of countermeasures that can be used during extended space missions in the setting of exposure to SPE radiation becomes a serious need. In the present study, we investigated the efficacy of enrofloxacin (an orally bioavailable antibiotic) and Granulocyte colony stimulating factor (G-CSF) (Neulasta) on enhancing resistance to Pseudomonas aeruginosa infection in mice subjected to HS and SPE-like radiation. The results revealed that treatment with enrofloxacin or G-CSF enhanced bacterial clearance and significantly decreased morbidity and mortality in challenged mice exposed to suspension and radiation. These results establish that antibiotics, such as enrofloxacin, and G-CSF could be effective countermeasures to decrease the risk of bacterial infections after exposure to SPE radiation during extended space flight, thereby reducing both the risk to the crew and the danger of mission failure. PMID:25793272

Li, Minghong; Holmes, Veronica; Ni, Houping; Sanzari, Jenine K.; Romero-Weaver, Ana L.; Lin, Liyong; Carabe-Fernandez, Alejandro; Diffenderfer, Eric S.; Kennedy, Ann R.; Weissman, Drew

2015-01-01

200

Fermenting debate: do yeast undergo apoptosis?  

Microsoft Academic Search

Apoptosis is a common feature of multicellular organisms. However, the recent observations of non-metazoan cell deaths displaying morphology reminiscent of apoptosis has suggested the existence of an ancestral cell death machinery. We discuss this possibility and its implications for the use of yeast in the dissection of the metazoan apoptotic process.

Andrew Fraser; Claerwen James

1998-01-01

201

Serine\\/Threonine Protein Kinases and Apoptosis  

Microsoft Academic Search

Over the past decade, our understanding of apoptosis, or programmed cell death, has increased greatly, with the identification of some of the major components of the apoptotic programme and the processes regulating their activation. Although apoptosis is an intrinsic process present in all cells, it can be regulated by extrinsic factors, including hormones, growth factors, cell surface receptors, and cellular

Timothy G. Cross; Dagmar Scheel-Toellner; Nick V. Henriquez; Elizabeth Deacon; Mike Salmon; Janet M. Lord

2000-01-01

202

CELL BIOLOGY: Apoptosis--the Calcium Connection  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Calcium ions are crucial to many cellular processes including apoptosis. In their Perspective, Demaurex and Distelhorst explain new work that shows how calcium ions flowing between the endoplasmic reticulum (ER) and mitochondria regulate programmed cell death, highlighting the ER as a new gateway to apoptosis (Scorrano et al.).

Nicolas Demaurex (University of Geneva Medical Center; Department of Physiology)

2003-04-04

203

THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY.  

EPA Science Inventory

The role of apoptosis in neurodegeneration in developing animals and in adults has become increasingly apparent in the past ten years. Normal apoptosis occurs in the CNS from the embryonic stage through senescence, with different cells in each region of the nervous system having ...

204

Apoptosis: A Review of Programmed Cell Death  

PubMed Central

The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis. PMID:17562483

Elmore, Susan

2007-01-01

205

Noninvasive real-time imaging of apoptosis  

Microsoft Academic Search

Strict coordination of proliferation and programmed cell death (apoptosis) is essential for normal physiology. An imbalance in these two opposing processes results in various diseases including AIDS, neurodegenerative disorders, myelodysplastic syndromes, ischemia\\/reperfusion injury, cancer, autoimmune disease, among others. Objective and quantitative noninvasive imaging of apoptosis would be a significant advance for rapid and dynamic screening as well as validation of

Bharathi Laxman; Daniel E. Hall; Mahaveer Swaroop Bhojani; Daniel A. Hamstra; Thomas L. Chenevert; Brian D. Ross; Alnawaz Rehemtulla

2002-01-01

206

HIV-1 induced bystander apoptosis.  

PubMed

Apoptosis of uninfected bystander cells is a key element of HIV pathogenesis and believed to be the driving force behind the selective depletion of CD4+ T cells leading to immunodeficiency. While several viral proteins have been implicated in this process the complex interaction between Env glycoprotein expressed on the surface of infected cells and the receptor and co-receptor expressing bystander cells has been proposed as a major mechanism. HIV-1 utilizes CD4 as the primary receptor for entry into cells; however, it is the viral co-receptor usage that greatly influences CD4 decline and progression to AIDS. This phenomenon is relatively simple for X4 viruses, which arise later during the course of the disease, are considered to be highly fusogenic, and cause a rapid CD4+ T cell decline. However, in contrast, R5 viruses in general have a greater transmissibility, are encountered early during the disease and have a lesser pathogenic potential than the former. The above generalization gets complicated in numerous situations where R5 viruses persist throughout the disease and are capable of causing a rigorous CD4+ T cell decline. This review will discuss the multiple factors that are reported to influence HIV induced bystander apoptosis and pathogenesis including Env glycoprotein phenotype, virus tropism, disease stage, co-receptor expression on CD4+ T cells, immune activation and therapies targeting the viral envelope. PMID:23202514

Garg, Himanshu; Mohl, Jonathon; Joshi, Anjali

2012-11-01

207

Lacidipine attenuates TNF-?-induced cardiomyocyte apoptosis.  

PubMed

This study was designed to investigate whether lacidipine elicited a protective role on cardiomyocyte against apoptosis induced by TNF-?. Neonatal rat cardiomyocytes were randomly assigned into different groups. TUNEL staining was utilized to detect apoptosis, and caspase-3 and caspse-12 were determined. To explore the underlying mechanism, Z-ATAD-FMK (a selective caspase-12 inhibitor) was used to identify the key molecule involved. TNF-? increased caspase-3 expression, which was mediated by increased caspase-12 expression. In the meantime, apoptosis was significantly induced by TNF-?. Lacidipine lowered caspase-12 and caspase-3 expression, and cardiomyocyte apoptosis induced by TNF-?. The results suggest that lacidipine attenuates TNF-? -induced apoptosis via inhibition of caspase-12 and caspase-3 successively. PMID:25226445

Wang, Qiu-Lin; Zhao, Lei; Feng, Na; Zhou, Peng; Wu, Qi; Fan, Rong; Li, Juan; Zhang, Shu-Miao; Wang, Yue-Min; Xu, Xue-Zeng; Yu, Shi-Qiang; Yi, Ding-Hua; Pei, Jian-Ming

2015-01-01

208

Apoptosis inducers in chronic lymphocytic leukemia  

PubMed Central

Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis and is still an incurable disease. Numerous apoptosis inducers have been described. These synthetic compounds and natural products (mainly derived from plants) display antileukemic properties in vitro and in vivo and some have even been tested in the clinic in CLL. They act through several different mechanisms. Most of them involve proteins of the Bcl-2 family, which are the key regulators in triggering the mitochondrial pathway of caspase-dependent apoptosis. Thus, the Mcl-1/Noxa axis appeared as a target. Here I overview natural and synthetic apoptosis inducers and their mechanisms of action in CLL cells. Opportunities for developing novel, apoptosis-based therapeutics are presented. PMID:24525395

Billard, Christian

2014-01-01

209

Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-?B-inducible immune pathways.  

PubMed

Erythropoietin (EPO) is the principal cytokine regulating erythropoiesis through its receptor, EPOR. Interestingly, EPORs are also found on immune cells with incompletely understood functions. Here, we show that EPO inhibits the induction of proinflammatory genes including tumor necrosis factor (TNF)-? and inducible nitric oxide (NO) synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor (NF)-?B p65 activation by EPO. Accordingly, in systemic Salmonella infection, treatment of mice with EPO results in reduced survival and impaired pathogen clearance because of diminished formation of anti-microbial effector molecules such as TNF-? and NO. However, neutralization of endogenous EPO or genetic ablation of Epor promotes Salmonella elimination. In contrast, in chemically induced colitis, EPO-EPOR interaction decreases the production of NF-?B-inducible immune mediators, thus limiting tissue damage and ameliorating disease severity. These immune-modulatory effects of EPO may be of therapeutic relevance in infectious and inflammatory diseases. PMID:21256055

Nairz, Manfred; Schroll, Andrea; Moschen, Alexander R; Sonnweber, Thomas; Theurl, Milan; Theurl, Igor; Taub, Nicole; Jamnig, Christina; Neurauter, Daniela; Huber, Lukas A; Tilg, Herbert; Moser, Patrizia L; Weiss, Günter

2011-01-28

210

Herbal medicines and infectious diseases: characterization by LC-SPE-NMR of some medicinal plant extracts used against malaria.  

PubMed

The extracts of two medicinal plants used in traditionalmedicine against malariawere characterized by means of an LC?SPE?NMR and LC?MS platform. The structure of a series of major constituents from Bafodeya benna, as well as minor constituents from Ormocarpum kirkii, was determined. Bafodeya benna was found to contain (2R,3R)-taxifolin-3-O-?-L-rhamnoside or astilbin, and its isomers neoastilbin, neoisoastilbin, and isoastilbin, as well as quercetin-3-O-?-L-rhamnoside. From Ormocarpum kirkii, a series of known flavonoids and biflavonoids was obtained, as well as three new compounds, i.e., 7,7??-di-O-?-D-glucosyl-(?)-chamaejasmin, 7-O-?-D-glucosyl-(I-3,II-3)-biliquiritigenin, and isovitexin-(I-3,II-3)-naringenin. The isolated constituents may explain, at least in part, the traditional use against malaria. LC?SPE?NMR, in combination with LC?MS, is a powerful tool for the fast characterization of plant extracts, in order to define priorities at an early stage of a fractionation procedure. In addition, herbal medicinal products can completely be characterized, both with regard to their major as well as their minor constituents. PMID:21328178

Xu, Yong-Jiang; Capistrano, Rica; Dhooghe, Liene; Foubert, Kenn; Lemière, Filip; Maregesi, Sheila; Baldé, Aliou; Apers, Sandra; Pieters, Luc

2011-07-01

211

Determination of the two major endocannabinoids in human plasma by ?-SPE followed by HPLC-MS/MS.  

PubMed

Endocannabinoids (ECs) are endogenous compounds that interact with type-1 and type-2 cannabinoid receptors (CB(1) and CB(2)), as well as non-cannabinoid receptors. The multitude of roles attributed to ECs makes them an emerging target of pharmacotherapy for a number of disparate diseases. Here a high-throughput bioanalytical method based on micro SPE (?-SPE) followed by LC-MS/MS analysis for the simultaneous determination of the two major endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide, AEA) in human plasma is presented. The chromatographic conditions obtained with the fused-core column allowed a good separation in 10 min also of the AG isomers. A very simple and reliable extraction has been optimised by means of C18-modified tips: it requires only 100 ?L of plasma and allows the use of minimal volumes of organic solvent. The present method allows a rapid and effective clean-up, which also minimises the isomerisation of 2-AG. The whole procedure has been validated following the FDA guidelines for bioanalytical methods validation: the satisfactory recovery values, the negligible matrix effect and the good values of accuracy and reproducibility make it a simple and high-throughput analytical tool for clinical and biochemical studies on endocannabinoid signaling in humans. PMID:22847477

Sergi, Manuel; Battista, Natalia; Montesano, Camilla; Curini, Roberta; Maccarrone, Mauro; Compagnone, Dario

2013-01-01

212

Development and optimization of the SPE procedure for determination of pharmaceuticals in water samples by HPLC-diode array detection.  

PubMed

This paper focuses on the investigation of different types of SPE sorbents for the preconcentration of eight veterinary pharmaceuticals from water samples. The pharmaceuticals studied were sulfamethazine, sulfadiazine, sulfaguanidine, trimethoprim, oxytetracycline, enrofloxacin, norfloxacin and penicillin G/procaine. Five different SPE materials (Strata-X, Strata-X-C, Strata SDB-L, Strata C8 and Strata C18) from Phenomenex were compared with Oasis HLB with a view to obtaining the best cartridges for all pharmaceuticals investigated. Extraction efficiency was determined by HPLC with diode array detection (DAD). HPLC-DAD separation and quantification of the selected pharmaceuticals were carried out under gradient elution by a binary mixture of 0.01 M oxalic acid and ACN based on cyano modified column (LiChrosphere 100 CN) from Merck. Strata-X provided the best results in the preconcentration of 100 mL water samples, yielding average pharmaceutical recoveries of higher than 90%, except for sulfaguanidine (76.1%). The developed Strata-X-HLPC-DAD method was validated and applied, for the efficient investigation of reverse osmosis/nanofiltration membranes and for the removal of these eight pharmaceuticals from the production wastewater samples. NF90 and XLE membranes were shown to be the best for the rejection of all investigated pharmaceuticals. PMID:20041448

Mutavdzi? Pavlovi?, Dragana; Babi?, Sandra; Dolar, Davor; Asperger, Danijela; Kosuti?, Kresimir; Horvat, Alka J M; Kastelan-Macan, Marija

2010-02-01

213

An automated SPE/LC/MS/MS method for the analysis of cocaine and metabolites in whole blood.  

PubMed

As laboratories are called upon to develop novel, fast, and sensitive methods, here we present a completely automated method for the analysis of cocaine and its metabolites (benzoylecgonine, ecgonine methyl ester, ecgonine and cocaethylene) from whole blood. This method utilizes an online solid-phase extraction (SPE) with high performance liquid chromatographic separation and tandem mass spectrometric detection. Pretreatment of samples involve only protein precipitation and ultracentrifugation. An efficient online solid-phase extraction (SPE) procedure was developed using Hysphere MM anion sorbent. A gradient chromatography method with a Gemini C6-Phenyl (50mmx3.00mm i.d., 5microm) column was used for the complete separation of all components. Analysis was by positive ion mode electrospray ionization tandem mass spectrometry, using multiple reaction monitoring (MRM) to enhance the selectivity and sensitivity of the method. For the analysis, two MRM transitions are monitored for each analyte and one transition is monitored for each internal standard. With a 30-microL sample injection, linearity was analyte dependent but generally fell between 8 and 500ng/mL. The limits of detection (LODs) for the method ranged from 3 to 16ng/mL and the limits of quantitation (LOQs) ranged from 8 to 47ng/mL. The bias and precision were determined using a simple analysis of variance (ANOVA: single factor). The results demonstrate bias as <7%, and %precision as <9% for all components at each QC level. PMID:18829399

Jagerdeo, Eshwar; Montgomery, Madeline A; Lebeau, Marc A; Sibum, Martin

2008-10-15

214

Development and validation of an on-line multidimensional SPE-LC-MS/MS method for the quantitation of Tetrandrine in blood samples.  

PubMed

On-line solid-phase extraction (SPE) is becoming an increasingly widespread technique in the clean-up of complex matrices such as body fluids, prior to chromatographic analysis. The use of small SPE columns instead of disposable SPE cartridges allows multiple injections and complete automation. In addition, it decreases the cost of consumables and improves the quality of the overall analysis. Coupling of SPE with HPLC combines sample preparation and separation in one system. In this paper a validated on-line multidimensional (MD) SPE-LC-MS/MS method is described for the determination of Tetrandrine (model drug) in human blood samples. The developed method showed the applicability of direct injection of plasma samples to an on-line MD-SPE-LC-MS/MS system to determine small molecules i.e. drugs. The experimental design is unique. Quantification was through tandem mass spectrometry with positive electrospray ionization (ESI) and multiple reactions monitoring (MRM). The limit of detection was calculated as 31.98ng/mL. The linear range of the method was between 40.0 and 800.0ng/mL. Pharmacokinetic parameters are usually determined by analysis of drug concentrations in plasma rather than whole blood. Parameters determined using plasma data may be misleading if concentrations of drug differ between plasma and red blood cells. We successfully applied the developed method for the determination of the distribution coefficient of the model drug Tetrandrine between human red blood cells and blood plasma proteins. The determination of distribution coefficient study results demonstrated that the developed method can provide direct and accurate measurement of RBC partitioning in a model drug and could be applied for screening of other compounds for potential high RBC partition, predicting potential drug toxicity and investigating mechanisms associated with RBC partitions. PMID:25746132

Caglar, Sena; Morello, Rosa; Boos, Karl-Siegfried

2015-04-15

215

NF B Inducers Upregulate cFLIP, a Cycloheximide-Sensitive Inhibitor of Death Receptor Signaling  

Microsoft Academic Search

The caspase 8 homologue FLICE-inhibitory protein (cFLIP) is a potent negative regulator of death receptor- induced apoptosis. We found that cFLIP can be upregulated in some cell lines under critical involvement of the NF-kB pathway, but NF-kB activation was clearly not sufficient for cFLIP induction in all cell lines. Treatment of SV80 cells with the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG-132)

SEBASTIAN KREUZ; DANIELA SIEGMUND; PETER SCHEURICH; HARALD WAJANT

2001-01-01

216

Transforming Growth Factor-b-induced Growth Inhibition in a Smad4 Mutant Colon Adenoma Cell Line1  

Microsoft Academic Search

Transforming growth factor-b (TGF-b) inhibits growth and induces apoptosis of colon epithelial cells. Binding of TGF-b to its receptor induces phosphorylation of the Smad proteins Smad2 and Smad3, which then form heteromeric complexes with Smad4, translocate to the nucleus, and activate gene transcription. Smad4 function has been considered an obli- gate requirement for TGF-b signaling, and Smad4 mutations present in

Stephen P. Fink; Sandra E. Swinler; James D. Lutterbaugh; Joan Massague; Sam Thiagalingam; Kenneth W. Kinzler; Bert Vogelstein; James K. V. Willson; Sanford Markowitz

217

Hyperthermia induces apoptosis in thymocytes  

SciTech Connect

Mild hyperthermia (43{degree}C for 1 h) induces extensive double-stranded DNA fragmentation and, at a later time, cell death in murine thymocytes. The cleavage of DNA into oligonucleosome-sized fragments resembles that observed in examples of apoptosis including radiation-induced death of thymocytes. Following hyperthermia, incubation at 37{degree}C is necessary to detect DNA fragmentation, although protein and RNA synthesis do not seem to be required. Two protein synthesis inhibitors, cycloheximide and emetine, and two RNA synthesis inhibitors, actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, do not inhibit DNA fragmentation or cell death in heated thymocytes at concentrations which significantly block these effects in irradiated thymocytes. We have used this difference in sensitivity to show that the DNA fragmentation induced in thymocytes which are irradiated and then heated seems to be caused only by the heating and not by the irradiation.

Sellins, K.S.; Cohen, J.J. (Univ. of Colorado School of Medicine, Denver (USA))

1991-04-01

218

APOPTOSIS: Death of a Monopoly?  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Hunot and Flavell discuss recent findings in Nature by Joza et al. that point to the existence of a new sort of cell death. Cell death is required during the development of an organism to remove portions of the body that will not be needed; this cell death usually requires destructive enzymes called caspases to perform the final demolition of the cell. But cavitation, an early developmental process in the mouse embryo that requires cell death, has now been suggested to occur through a caspase-independent pathway that instead uses a mitochondrial protein called AIF (apoptosis-inducing factor).

Stéphane Hunot (Yale University School of Medicine; Section of Immunobiology and the Howard Hughes Medical Institute)

2001-05-04

219

Apoptosis: programmed cell death in fetal development.  

PubMed

Controlled death of cells is as much a part of embryonal development as is cell proliferation and differentiation. This cell suicide is controlled by cell genes involved in induction or prevention of programmed cell death (PCD). During embryogenesis PCD implicates cell elimination, necessary in fashioning of the body, moulding of tissues. PCD is often used synonymous with the designation apoptosis, which indicates an endogenous cell suicide program by which useless or crippled cells are eliminated. Apoptosis occurs in normal tissue turnover, in organ involution after withdrawal of trophic hormones, in distinct cells after deprivation of growth factors or specific stimuli and in cells which have undergone sublethal damage. During PCD the nucleus breaks up into DNA fragments of 180-200 kD and the endoplasmic reticulum transforms into vesicles, which are released as apoptotic bodies into the extracellular space. The apoptotic bodies, containing cell organelles and nuclear fragments, are phagocytosed by neighboring cells. Electron micrographs of embryos have revealed the presence of numerous cells with the characteristic features of apoptosis. Experiments, in which small tissue fragments were explanted to other regions, have proven that focal apoptosis is under control of genetic, hormonal and local tissue factors. Morphological analysis has shown that most of the ovarian follicles undergo during development apoptosis, resulting in follicle atresia. Only a small proportion escapes PCD. Growth factors and estrogens have been identified as follicle survival factors, androgens and gonadotropin releasing hormones are potentiating apoptosis of the follicle. An exaggerated PCD or a defective apoptosis during embryogenesis may cause developmental abnormalities. Certain viruses can inhibit apoptosis, while metabolic stress or damage of cell structures can induce apoptosis. Therefore not only viral infections, also drugs and chemical or physical injuries during embryogenesis may interfere with the balanced PCD and thus induce malformations. Drugs and therapy designs directed to modulate the apoptotic process will offer new approaches to the prevention of congenital malformations. PMID:8801138

Haanen, C; Vermes, I

1996-01-01

220

Lamin proteolysis facilitates nuclear events during apoptosis  

PubMed Central

Expression of the adenovirus E1A oncogene stimulates both cell proliferation and p53-dependent apoptosis in rodent cells. p53 implements apoptosis in all or in part through transcriptional activation of bax, the product of which promotes cell death. The adenovirus E1B 19K product is homologous in sequence and in function to Bcl-2, both of which bind to and inhibit the activity of Bax and thereby suppress apoptosis. The E1B 19K protein also interacts with the nuclear lamins, but the role of this interaction in the regulation of apoptosis is not known. Lamins are, however, substrates for members of the interleukin-1 beta-converting enzyme (ICE) family of cysteine proteases that are activated during apoptosis and function downstream of Bcl-2 in the cell death pathway. lamins are degraded during E1A- induced p53-dependent apoptosis. Lamin A and C are cleaved into 47- and 37-kD fragments, respectively, and the site of proteolysis is mapped to a conserved aspartic acid residue at position 230. The cleavage of lamins during apoptosis is consistent with the activation of an ICE- related cysteine protease down-stream of p53. No lamin protease activity was detected in cells expressing the E1B 19K protein, indicating that 19K functions upstream of protease activation in inhibiting apoptosis. Substitution of the aspartic acid at the cleavage site produced a mutant lamin protein that was resistant to proteolysis both in vitro and in vivo. Expression of uncleavable mutant lamin A or B attenuated apoptosis, delaying cell death and the associated DNA fragmentation by 12 h. Mutant lamin expressing cells failed to show the signs of chromatin condensation and nuclear shrinkage typical of cell death by apoptosis. Instead, the nuclear envelope collapsed and the nuclear lamina remained intact. However, the late stage of apoptosis was morphologically unaltered and formation of apoptotic bodies was evident. Thus, lamin breakdown by proteolytic degradation facilitates the nuclear events of apoptosis perhaps by facilitating nuclear breakdown. PMID:8978814

1996-01-01

221

Modeling heterogeneous responsiveness of intrinsic apoptosis pathway  

PubMed Central

Background Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism’s survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level. Results To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of molecular numbers. Furthermore, the extrinsic noise represented by random variations of two key apoptotic proteins, namely Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or in combination with intrinsic noise. The resultant stochasticity in the timing of intrinsic apoptosis response shows that the fluctuating protein variations can induce cell-to-cell stochastic variability at a quantitative level agreeing with experiments. Finally, simulations illustrate that the mean abundance of fluctuating IAP protein is positively correlated with the degree of cellular stochasticity of the intrinsic apoptosis pathway. Conclusions Our theoretical and computational study shows that the pronounced non-genetic heterogeneity in intrinsic apoptosis responses among individual cells plausibly arises from extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts that the IAP protein could serve as a potential therapeutic target for suppression of the cell-to-cell variation in the intrinsic apoptosis responsiveness. PMID:23875784

2013-01-01

222

Induction of germline apoptosis in Caenorhabditis elegans.  

PubMed

RNA interference (RNAi) is an incredibly powerful tool for rapid and efficient knockdown of gene expression. This technology can be used to induce apoptosis in the germline of Caenorhabditis elegans. Genotoxic stressors such as ionizing radiation (IR), ultraviolet light, chemical mutagens (e.g., N-ethyl-N-nitrosourea [ENU]), and DNA cross-linking reagents can also be used to stimulate apoptosis. These approaches, described here, combined with the powers of in vivo imaging methods, should keep C. elegans apoptosis researchers busy for several years, sorting out how various signaling pathways influence life and death decisions in this organism. PMID:24591690

Lant, Benjamin; Derry, W Brent

2014-03-01

223

A Caspase-Related Protease Regulates Apoptosis in Yeast  

Microsoft Academic Search

Yeast can undergo cell death accompanied by cellular markers of apoptosis. However, orthologs of classical mammalian apoptosis regulators appeared to be missing from the yeast genome, challenging a common mechanism of yeast and mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein. Hydrogen peroxide treatment induces apoptosis

Frank Madeo; Eva Herker; Corinna Maldener; Silke Wissing; Stephan Lächelt; Mark Herlan; Markus Fehr; Kirsten Lauber; Stephan J Sigrist; Sebastian Wesselborg; Kai-Uwe Fröhlich

2002-01-01

224

Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells  

Microsoft Academic Search

Purpose: Apoptosis is currently being evaluated for its importance as a pathway of radiation-induced cell death. However, the difference in the mechanisms between premitotic and postmitotic apoptosis following X-irradiation remains not well understood. We show here that the human monoblastoid cell line U937 can be induced to undergo these two different types of apoptosis.Methods and Materials: U937 cells were irradiated

Nariyoshi Shinomiya; Yukie Kuno; Fuyumi Yamamoto; Masashi Fukasawa; Atsushi Okumura; Megumi Uefuji; Makoto Rokutanda

2000-01-01

225

Novel Apoptosis-Inducing Activity in Bacteroides forsythus: a Comparative Study with Three Serotypes of Actinobacillus actinomycetemcomitans  

PubMed Central

Bacteroides forsythus, which has been reported to be associated with periodontitis but has not been recognized as a key pathogen, was found to induce cytolytic activity against HL-60 and other human leukemic cells. This cytolytic activity was demonstrated according to three different criteria: (i) loss of both mitochondrial membrane potential and membrane integrity in cells treated with bacterial extracts and then with Rh123 and propidium iodide, respectively, as demonstrated by flow cytometry; (ii) damage to cytoplasmic membrane, as revealed by scanning electron microscopy (SEM); and (iii) DNA ladder formation and activation of caspase-3. These results indicate that B. forsythus produced an apoptosis-inducing factor(s) found to be composed of protein as judged by heat and trypsin sensitivity. In addition to extracts from B. forsythus, the culture supernatant of this bacterium has the ability to induce a cytolytic effect against peripheral white blood cells, especially lymphocytes. For comparison with B. forsythus, the same analyses were applied to two strains with different serotypes of Actinobacillus actinomycetemcomitans, serotypes a (ATCC 43717) and c (ATCC 43719), in addition to previously reported apoptosis-inducing serotype b (ATCC 43718), which was used as a positive control. The strains of A. actinomycetemcomitans serotypes a and b induced apoptosis in HL-60 cells as judged by the above three criteria but to a slightly lesser extent than did B. forsythus, while the serotype c strain produced apoptosis to a negligible extent. Detailed SEM images showed that the A. actinomycetemcomitans serotype a strain induced large-pore formation and the serotype b strain produced small pores with typical blebbing, while B. forsythus induced severe membrane ruffling. Further DNA ladder formation and caspase-3 activation were observed in the serotype a and b strains but not in the serotype c strain. The present paper is the first report of a protein factor(s) from B. forsythus and the A. actinomycetemcomitans serotype a strain which induces apoptotic cell death. PMID:10899863

Arakawa, Shinichi; Nakajima, Takuma; Ishikura, Hiroaki; Ichinose, Shizuko; Ishikawa, Isao; Tsuchida, Nobuo

2000-01-01

226

In situ apoptosis in the thyroid.  

PubMed

Recent evidence has emphasized the importance of programmed cell death, or apoptosis, in the maintenance of tissue homeostasis and pathogenesis of tumors. This study analyzed the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, and tissue histology in thyroid tissue. Extent of apoptosis was defined by morphological criteria and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate (dUTP) biotin nick end labeling (TUNEL) assay. Immunocytochemistry was performed for p53, bcl-2, and Ki-67 expression. There was good correlation between TUNEL-reactive cells and morphological evaluation criteria for apoptosis. The extent of apoptosis was significantly associated with the type of thyroid lesion (r = 0.66990, p = 0.000012), both proliferative (namely multinodular goiter) and neoplastic (benign and malignant). A higher extent of apoptosis was evident in medullary and anaplastic carcinomas. Apoptosis also correlated to p53 protein accumulation (r = 0.485, p = 0.00041) and Ki-67 immunoreactivity (r = 0.435, p = 0.001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). By inhibiting apoptosis, bcl-2, may cause a shift in tissue kinetics toward the preservation of genetically aberrant cells, thereby facilitating tumor progression. These results imply that rapidly proliferating tumors appear to have a high cell turnover state in which there may be increased chance of apoptosis among the proliferating cells. The ability of apoptosis to occur in the presence of a possibly mutant p53 protein suggest the existence of at least two p53 dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it. However, keeping in mind the limited number of subjects studied in each subgroup and the rather low correlation coefficients, these possibilities would have to be substantiated in a larger study population. PMID:10718547

Sreelekha, T T; Pradeep, V M; Vijayalakshmi, K; Belthazar, A; Chellam, V G; Nair, M B; Pillai, M R

2000-02-01

227

Activation of Human Herpesvirus Replication by Apoptosis  

PubMed Central

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance. PMID:23885073

Prasad, Alka; Remick, Jill

2013-01-01

228

APOPTOSIS: A Cinderella Caspase Takes Center Stage  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. It has been thought that permeabilization of mitochondria and release of cytochrome c is an early event in apoptosis that is required for activation of caspases, the enzyme executioners of the apoptotic cascade. However, in a Perspective, Kumar and Vaux explain new findings (Lassus et al.) that implicate an often ignored caspase, caspase-2, in the early stages of apoptosis prior to mitochondrial permeabilization.

Sharad Kumar (Hanson Institute; )

2002-08-23

229

Inhibition of glomerular cell apoptosis by heparin  

Microsoft Academic Search

Inhibition of glomerular cell apoptosis by heparin.BackgroundHeparin, the multifunctional glycosaminoglycan, has been considered a therapeutic agent for glomerular diseases. Although a number of biological properties are postulated to explain its therapeutic utility, it is unknown whether heparin affects cell survival in the glomerulus. In this report, we investigated the effect of heparin on apoptosis of glomerular cells.MethodsCultured rat mesangial cells

Yoshihisa Ishikawa; Masanori Kitamura

1999-01-01

230

Apoptosis: A Way to Maintain Healthy Individuals  

Microsoft Academic Search

\\u000a Apoptosis, the best known form of programmed cell death, is tightly regulated by a number of sensors, signal transducers and\\u000a effectors. Apoptosis is mainly active during embryonic development, when deletion of redundant cellular material is required\\u000a for the correct morphogenesis of tissues and organs; moreover, it is essential for the maintenance of tissue homeostasis during\\u000a cell life. Cells also activate

Chiara Mondello; A. Ivana Scovassi

231

WDM compatible and electrically tunable SPE-OCDMA system based on the temporal self-imaging effect.  

PubMed

A coding/decoding setup for a spectral phase encoding optical code-division multiple access (SPE-OCDMA) system has been developed. The proposal is based on the temporal self-imaging effect and the use of an easily tunable electro-optic phase modulator to achieve line-by-line coding of the transmitted signal, thus assuring compatibility with WDM techniques. Modulation of the code is performed at the same rate as the data, avoiding the use of high-bandwidth electro-optic modulators. As proof of concept of the technique, experimental results are presented for a back-to-back coder/decoder setup transmitting a 10 GHz unmodulated optical pulse train within an 80 GHz optical window and using 8-chip Hadamard codes. PMID:21283203

Tainta, S; Amaya, W; Erro, M J; Garde, M J; Sales, S; Muriel, M A

2011-02-01

232

Mathematical modeling and statistical analysis of SPE-OCDMA systems utilizing second harmonic generation effect in thick crystal receivers  

NASA Astrophysics Data System (ADS)

In this paper we analytically study and evaluate the performance of a Spectral-Phase-Encoded Optical CDMA system for different parameters such as the user's code length and the number of users in the network. In this system an advanced receiver structure in which the Second Harmonic Generation effect imposed in a thick crystal is employed as the nonlinear pre-processor prior to the conventional low speed photodetector. We consider ASE noise of the optical amplifiers, effective in low power conditions, besides the multiple access interference (MAI) noise which is the dominant source of noise in any OCDMA communications system. We use the results of the previous work which we analyzed the statistical behavior of the thick crystals in an optically amplified digital lightwave communication system to evaluate the performance of the SPE-OCDMA system with thick crystals receiver structure. The error probability is evaluated using Saddle-Point approximation and the approximation is verified by Monte-Carlo simulation.

Matinfar, Mehdi D.; Salehi, Jawad A.

2009-11-01

233

Copyright 2004, Society of Petroleum Engineers, Inc. This paper was prepared for presentation at the SPE Formation Damage Conference held in  

E-print Network

SPE 86526 Copyright 2004, Society of Petroleum Engineers, Inc. This paper was prepared by the Society of Petroleum Engineers and are subject to correction by the author(s). The material, as presented, does not necessarily reflect any position of the Society of Petroleum Engineers, its officers

234

Copyright 2007, Society of Petroleum Engineers This paper was prepared for presentation at the SPE Europec/EAGE Annual Conference and  

E-print Network

Copyright 2007, Society of Petroleum Engineers This paper was prepared for presentation at the SPE by the Society of Petroleum Engineers and are subject to correction by the author(s). The material, as presented, does not necessarily reflect any position of the Society of Petroleum Engineers, its officers

235

Advantages of on-line SPE coupled with UPLC/MS/MS1 for determining the fate of pesticides and2  

E-print Network

1 Advantages of on-line SPE coupled with UPLC/MS/MS1 for determining the fate of pesticides and2 techniques were validated for both 18 pesticides22 and their degradates and 17 pharmaceuticals for pesticides and24 metabolites have been obtained, with linearity range up to 1 µg.L-1.The limits of25

Paris-Sud XI, Université de

236

Physics-based Reconstruction of Sedimentary Rocks Guodong Jin, UC Berkeley; Tad W. Patzek, SPE, UC Berkeley / Lawrence Berkeley National Laboratory; and Dmitry B. Silin,  

E-print Network

SPE 83587 Physics-based Reconstruction of Sedimentary Rocks Guodong Jin, UC Berkeley; Tad W. Patzek that reconstructs nu- merically the geometrical structure and mechanical prop- erties of natural sedimentary rocks a reconstruction that resembles as closely as possible a given sedimentary rock with respect to its geometric

Patzek, Tadeusz W.

237

Correction of predicted concentration in the use of solvent-based calibration lines for determining carbendazim, fuberidazole and thiabendazole in water after a SPE step.  

PubMed

This paper addresses an attempt to overcome the deviation that results from the use of a solid phase extraction (SPE) procedure for extracting trace levels of three benzimidazole pesticides (carbendazim, fuberidazole and thiabendazole) from water samples, for their subsequent quantitative determination by spectrofluorimetry, using univariate calibration. The deviation is due to an attenuation effect originating in the C(18) cartridge used in the SPE step. The approach developed is based on the calculation of a correction factor (fc) that is dependent on the signal measured after the SPE step. In order to calculate fc a study of the intermediate precision of two calibration graphs (with and without SPE) was performed. The fc was added to the predicted concentrations for the analytes using a calibration graph for pure solvent, built every time that the analysis is done. In addition, predictions were made using both average calibration graphs obtained from the intermediate precision study. In this study, the first of these three options was shown to improve the accuracy of predictions in the presence of matrix effects. PMID:18969056

Picón Zamora, D; Martínez Vidal, J L; Marínez Galera, M; Garrido Frenich, A; López González, J L; Arahal, M R

2003-06-13

238

Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop  

SciTech Connect

Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 {angstrom} resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC{sub 50} values for trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.

González-Páez, Gonzalo E.; Wolan, Dennis W. (Scripps)

2012-09-05

239

Effect of SPE-like Proton or Photon Radiation on the Kinetics of Mouse Peripheral Blood Cells and Radiation Biological Effectiveness Determinations  

PubMed Central

Abstract Exploration missions outside low-Earth orbit are being planned; therefore, it is critical to understand the risk astronauts would be exposed to in the space environment, especially during extravehicular activities (EVAs). Reductions in white blood cell (WBC) numbers can occur as a result of exposure to solar particle event (SPE) radiation. The aim of the present study was to determine the duration of the effects on blood cell numbers from exposure to a single whole-body dose of SPE-like proton radiation or photon radiation as well as to determine the radiation biological effectiveness (RBE) values at those times when radiation exposure causes blood cell numbers to experience the most critical effects when using mice as a model. Our results indicate that both types of radiation cause significant reductions in the numbers of all blood cell types at different times post-irradiation. The RBE values were not significantly different from 1.0. These results indicate that the risk estimations for astronauts from exposure of mice to SPE-like proton radiation are comparable to those previously made for doses of standard reference radiations, suggesting that countermeasures should be developed for the decreases in blood cell counts observed following the exposure of mice to SPE radiation. Key Words: Proton radiation—Gamma radiation—Blood cell counts—Solar particle event. Astrobiology 13, 570–577. PMID:23980767

Romero-Weaver, A.L.; Wan, X.S.; Diffenderfer, E.S.; Lin, L.

2013-01-01

240

Umbelliprenin Induces Apoptosis in CLL Cell Lines  

PubMed Central

Chronic lymphocytic leukemia (CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Many Ferula species, including F. asa-foetida, synthesize terpenyloxy coumarins. One of these coumarins is umbelliprenin, which has been implicated with induction of apoptosis in some cancer cell lines. In this study induction of apoptosis by umbelliprenin on Jurkat T-CLL and Raji B-CLL cell lines was studied. In this regard, cells were incubated with various concentrations of umbelliprenin in-vitro for different times and assayed for apoptosis with annexin V–FITC/PI double staining flowcytometry method. Results showed that umbelliprenin induced apoptosis in leukemic cells in a dose- and time-dependent manner and that CLL cells were more susceptible to umbelliprenin induced cell death than normal peripheral blood mononuclear cell (PBMCs). Moreover, we study the induction of apoptosis in Jurkat cells by umbelliprenin in the presence of interleukin 4 (IL-4) as an agent that causes resistance to apoptosis in CLL cells, was also student. We showed that IL-4 can not reduce apoptotic effect of umbelliprenin. The preferential toxicity of umbelliprenin for CLL cells, supports the hypothesis that oral administration of umbelliprenin in the form of foods or folk medicines containing this coumarin, might enhance protection against the development of CLL in man with little side effects. In conclusion, umbelliprenin may be an effective therapeutic agent in the treatment of CLL, and thus clinical studies with umbelliprenin may be appropriate. PMID:24250490

Ziai, Seyed Ali; Gholami, Omid; Iranshahi, Mehrdad; Zamani, Amir Hassan; Jeddi-Tehrani, Mahmood

2012-01-01

241

X-Linked Inhibitor of Apoptosis Regulates Lung Fibroblast Resistance to Fas-Mediated Apoptosis  

PubMed Central

The accumulation of apoptosis-resistant fibroblasts within fibroblastic foci is a characteristic feature of idiopathic pulmonary fibrosis (IPF), but the mechanisms underlying apoptosis resistance remain unclear. A role for the inhibitor of apoptosis (IAP) protein family member X-linked inhibitor of apoptosis (XIAP) has been suggested by prior studies showing that (1) XIAP is localized to fibroblastic foci in IPF tissue and (2) prostaglandin E2 suppresses XIAP expression while increasing fibroblast susceptibility to apoptosis. Based on these observations, we hypothesized that XIAP would be regulated by the profibrotic mediators transforming growth factor (TGF)?-1 and endothelin (ET)-1 and that increased XIAP would contribute to apoptosis resistance in IPF fibroblasts. To address these hypotheses, we examined XIAP expression in normal and IPF fibroblasts at baseline and in normal fibroblasts after treatment with TGF-?1 or ET-1. The role of XIAP in the regulation of fibroblast susceptibility to Fas-mediated apoptosis was examined using functional XIAP antagonists and siRNA silencing. In concordance with prior reports, fibroblasts from IPF lung tissue had increased resistance to apoptosis compared with normal lung fibroblasts. Compared with normal fibroblasts, IPF fibroblasts had significantly but heterogeneously increased basal XIAP expression. Additionally, TGF-?1 and ET-1 induced XIAP protein expression in normal fibroblasts. Inhibition or silencing of XIAP enhanced the sensitivity of lung fibroblasts to Fas-mediated apoptosis without causing apoptosis in the absence of Fas activation. Collectively, these findings support a mechanistic role for XIAP in the apoptosis-resistant phenotype of IPF fibroblasts. PMID:23492187

Ajayi, Iyabode O.; Sisson, Thomas H.; Higgins, Peter D. R.; Booth, Adam J.; Sagana, Rommel L.; Huang, Steven K.; White, Eric S.; King, Jessie E.; Moore, Bethany B.

2013-01-01

242

Apoptosis and the antiphospholipid syndrome.  

PubMed

The target of many antiphospholipid autoantibodies (APA) has been shown to be a complex between anionic phospholipid (PL) and the plasma protein beta 2-glycoprotein I (beta 2-GPI), but the identity of the natural target(s) and/or immunogen for APA in vivo remains undetermined. The anionic PL of cell membranes represent important potential targets and immunogenes for APA. Although anionic PL are normally absent from the extracellular surface of cell membranes, they redistribute from the inner to the outer leaflet during apoptosis. We and others have shown that beta 2-GPI binds selectively to the surface of apoptotic, but not viable, cells, and that the binding of beta 2-GPI to the surface of apoptotic cells generates an epitope recognized by APA from patients with both primary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). In this review, we discuss recent findings, which suggest not only that apoptotic cell-bound beta 2-GPI is injected by non-intravenous routes. We also review briefly the potential role of oxidation in generating epitopes responsible for the recognition and induction of APA. Taken together, we believe that the available evidence supports a role for apoptotic cells as far as targets of APA and possible players in the induction of APA. PMID:10968916

Rauch, J; Subang, R; D'Agnillo, P; Koh, J S; Levine, J S

2000-09-01

243

NF-?B-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis  

PubMed Central

Angiogenesis is essential during development and in pathological conditions such as chronic inflammation and cancer progression. Inhibition of angiogenesis by targeting vascular endothelial growth factor (VEGF) blocks disease progression, but most patients eventually develop resistance which may result from compensatory signalling pathways. In endothelial cells (ECs), expression of the pro-angiogenic chemokine CXCL12 is regulated by non-canonical nuclear factor (NF)-?B signalling. Here, we report that NF-?B-inducing kinase (NIK) and subsequent non-canonical NF-?B signalling regulate both inflammation-induced and tumour-associated angiogenesis. NIK is highly expressed in endothelial cells (ECs) in tumour tissues and inflamed rheumatoid arthritis synovial tissue. Furthermore, non-canonical NF-?B signalling in human microvascular ECs significantly enhanced vascular tube formation, which was completely blocked by siRNA targeting NIK. Interestingly, Nik?/? mice exhibited normal angiogenesis during development and unaltered TNF?- or VEGF-induced angiogenic responses, whereas angiogenesis induced by non-canonical NF-?B stimuli was significantly reduced. In addition, angiogenesis in experimental arthritis and a murine tumour model was severely impaired in these mice. These studies provide evidence for a role of non-canonical NF-?B signalling in pathological angiogenesis, and identify NIK as a potential therapeutic target in chronic inflammatory diseases and tumour neoangiogenesis. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25043127

Noort, Ae R; van Zoest, Katinka PM; Weijers, Ester M; Koolwijk, Pieter; Maracle, Chrissta X; Novack, Deborah V; Siemerink, Martin J; Schlingemann, Reinier O; Tak, Paul P; Tas, Sander W

2014-01-01

244

Nitric Oxide Functions as a Signal in Ultraviolet-B-Induced Baicalin Accumulation in Scutellaria baicalensis Suspension Cultures  

PubMed Central

Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, N?-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation. PMID:24646913

Zhang, Jin-Jie; Li, Xue-Qin; Sun, Jun-Wei; Jin, Song-Heng

2014-01-01

245

Antiviral signaling protein MITA acts as a tumor suppressor in breast cancer by regulating NF-?B induced cell death.  

PubMed

Emerging evidences suggest that chronic inflammation is one of the major causes of tumorigenesis. The role of inflammation in regulation of breast cancer progression is not well established. Recently Mediator of IRF3 Activation (MITA) protein has been identified that regulates NF-?B and IFN pathways. Role of MITA in the context of inflammation and cancer progression has not been investigated. In the current report, we studied the role of MITA in the regulation of cross talk between cell death and inflammation in breast cancer cells. The expression of MITA was significantly lower on in estrogen receptor (ER) positive breast cancer cells than ER negative cells. Similarly, it was significantly down regulated in tumor tissue as compared to the normal tissue. The overexpression of MITA in MCF-7 and T47D decreases the cell proliferation and increases the cell death by activation of caspases. MITA positively regulates NF-?B transcription factor, which is essential for MITA induced cell death. The activation of NF-?B induces TNF-? production which further sensitizes MITA induced cell death by activation of death receptor pathway through capsase-8. MITA expression decreases the colony forming units and migration ability of MCF-7 cells. Thus, our finding suggests that MITA acts as a tumor suppressor which is down regulated during tumorigenesis providing survival advantage to tumor cell. PMID:24239807

Bhatelia, Khyati; Singh, Aru; Tomar, Dhanendra; Singh, Kritarth; Sripada, Lakshmi; Chagtoo, Megha; Prajapati, Paresh; Singh, Rochika; Godbole, Madan M; Singh, Rajesh

2014-02-01

246

Interaction of COP1 and UVR8 regulates UV-B-induced photomorphogenesis and stress acclimation in Arabidopsis  

PubMed Central

The ultraviolet-B (UV-B) portion of the solar radiation functions as an environmental signal for which plants have evolved specific and sensitive UV-B perception systems. The UV-B-specific UV RESPONSE LOCUS 8 (UVR8) and the multifunctional E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) are key regulators of the UV-B response. We show here that uvr8-null mutants are deficient in UV-B-induced photomorphogenesis and hypersensitive to UV-B stress, whereas overexpression of UVR8 results in enhanced UV-B photomorphogenesis, acclimation and tolerance to UV-B stress. By using sun simulators, we provide evidence at the physiological level that UV-B acclimation mediated by the UV-B-specific photoregulatory pathway is indeed required for survival in sunlight. At the molecular level, we demonstrate that the wild type but not the mutant UVR8 and COP1 proteins directly interact in a UV-B-dependent, rapid manner in planta. These data collectively suggest that UV-B-specific interaction of COP1 and UVR8 in the nucleus is a very early step in signalling and responsible for the plant's coordinated response to UV-B ensuring UV-B acclimation and protection in the natural environment. PMID:19165148

Favory, Jean-Jacques; Stec, Agnieszka; Gruber, Henriette; Rizzini, Luca; Oravecz, Attila; Funk, Markus; Albert, Andreas; Cloix, Catherine; Jenkins, Gareth I; Oakeley, Edward J; Seidlitz, Harald K; Nagy, Ferenc; Ulm, Roman

2009-01-01

247

Pre-Shot Simulations of Far-Field Ground Motions for the Source Physics Experiment (SPE) Explosions at the Climax Stock, Nevada National Security Site  

SciTech Connect

The Source Physics Experiment (SPE) will involve a series of explosions in various geologic and emplacement conditions to validate numerical simulation methods to predict behavior of seismic wave excitation and propagation for nuclear test monitoring. The first SPE's currently underway involve explosions in the Climax Stock (granitic geology) at the Nevada National Security Site (NNSS). Detailed geologic data and published material properties for the major lithologic units of the NNSS and surrounding region were used to build three-dimensional models for seismic wave propagation simulations. The geologic structure near the SPE shot point is quite varied including granitic, carbonate, tuff and alluvium lithologies. We performed preliminary ground motion simulations for a near-source domain covering 8 km x 8 km at the surface centered on the shot point to investigate various source and propagation effects using WPP, LLNL's anelastic seismic wave finite difference code. Simulations indicate that variations in wave propagation properties of the sub-surface will generate strongly path-dependent response once the energy has left the relatively small granitic geology of the near-surface Climax Stock near the SPE shot point. Rough topography to the north and west of SPE shot point causes additional complexity in the signals including energy on the transverse components. Waves propagate much faster through the granitic and carbonate formations and slower through the tuff and alluvium. Synthetic seismograms for a pure explosion source in a 3D geologic structure show large amplitudes on transverse component. For paths to the south sampling the granite, tuff and alluvium lithologies transverse component amplitudes are as high as 50% of that on the vertical and radial components.

Rodgers, A J; Wagoner, J; Petersson, N A; Sjogreen, B

2010-11-07

248

Liquid Metering Centrifuge Sticks (LMCS): A Centrifugal Approach to Metering Known Sample Volumes for Colorimetric Solid Phase Extraction (C-SPE)  

NASA Technical Reports Server (NTRS)

Phase separation is one of the most significant obstacles encountered during the development of analytical methods for water quality monitoring in spacecraft environments. Removing air bubbles from water samples prior to analysis is a routine task on earth; however, in the absence of gravity, this routine task becomes extremely difficult. This paper details the development and initial ground testing of liquid metering centrifuge sticks (LMCS), devices designed to collect and meter a known volume of bubble-free water in microgravity. The LMCS uses centrifugal force to eliminate entrapped air and reproducibly meter liquid sample volumes for analysis with Colorimetric Solid Phase Extraction (C-SPE). C-SPE is a sorption-spectrophotometric platform that is being developed as a potential spacecraft water quality monitoring system. C-SPE utilizes solid phase extraction membranes impregnated with analyte-specific colorimetric reagents to concentrate and complex target analytes in spacecraft water samples. The mass of analyte extracted from the water sample is determined using diffuse reflectance (DR) data collected from the membrane surface and an analyte-specific calibration curve. The analyte concentration can then be calculated from the mass of extracted analyte and the volume of the sample analyzed. Previous flight experiments conducted in microgravity conditions aboard the NASA KC-135 aircraft demonstrated that the inability to collect and meter a known volume of water using a syringe was a limiting factor in the accuracy of C-SPE measurements. Herein, results obtained from ground based C-SPE experiments using ionic silver as a test analyte and either the LMCS or syringes for sample metering are compared to evaluate the performance of the LMCS. These results indicate very good agreement between the two sample metering methods and clearly illustrate the potential of utilizing centrifugal forces to achieve phase separation and metering of water samples in microgravity.

Gazda, Daniel B.; Schultz, John R.; Clarke, Mark S.

2007-01-01

249

Transgenic Overexpression of cdx1b Induces Metaplastic Changes of Gene Expression in Zebrafish Esophageal Squamous Epithelium  

PubMed Central

Abstract Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish. PMID:23672288

Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J.

2013-01-01

250

Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation  

PubMed Central

Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (D?Np53). Historically, D?Np53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that D?Np53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and D?Np53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of D?Np53 induced Wingless (Wg) expression and enhanced proliferation in both ‘undead cells' and in ‘genuine' apoptotic cells. In contrast to D?Np53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that D?Np53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology. PMID:22898807

Dichtel-Danjoy, M-L; Ma, D; Dourlen, P; Chatelain, G; Napoletano, F; Robin, M; Corbet, M; Levet, C; Hafsi, H; Hainaut, P; Ryoo, H D; Bourdon, J-C; Mollereau, B

2013-01-01

251

Regulation of membrane release in apoptosis.  

PubMed Central

Apoptosis is a fundamental process of cell regulation whereby cells execute one or more biochemical programs leading to cell death. Several mechanisms have been evaluated and suggested to play roles in the regulation of apoptosis, including the activation of phospholipase A2 (PLA2), usually measured as release of 3H-labelled arachidonic acid (AA) from prelabelled cells. The current study was aimed at examining the role of PLA2 in regulating apoptosis in response to several inducers (such as vincristine and etoposide) in lymphoid cell lines. Cells were labelled with [3H]fatty acids and the released radioactivity was characterized. These studies indicated that the AA release assay did not reflect release of non-esterified fatty acid via activation of the PLA2 pathway. Rather, studies using TLC and electron microscopy showed that AA release reflected a previously unsuspected shedding of a heterogeneous population of membrane vesicles and fragments, probably as components of apoptotic bodies. Further studies demonstrated that this process is an integral part of apoptosis. Overexpression of Bcl-2 or the addition of caspase peptide inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethane prevented the characteristic morphological changes of cell death, and completely inhibited the release of membrane vesicles and fragments. On the other hand, release of membrane vesicles and fragments was caused by various inducers of apoptosis, as measured by release of either 3H-labelled AA or palmitic acid. Thus the present study demonstrates that the release of membrane lipids during apoptosis defines a new assay for apoptosis and has allowed the investigation of the mechanisms regulating formation of apoptotic bodies. PMID:9716508

Zhang, J; Driscoll, T A; Hannun, Y A; Obeid, L M

1998-01-01

252

[Analysis of the mechanism of apoptosis induction by PSK].  

PubMed

Previously, we reported that PSK induces apoptosis and growth inhibition in HL60 cells. In this study, we tried to clarify the mechanism of how PSK induces apoptosis. Because several reports suggested that apoptosis of HL60 cells is mediated by activation of p38MAPK, we examined whether p38MAPK is involved in PSK-induced apoptosis. First, we found that PSK induced p38MAPK phosphorylation, which is considered as its activation. Next, we demonstrated that SB203580, inhibitor of p38MAPK, inhibited PSK-induced apoptosis. These results suggest that p38MAPK plays an important role in PSK-induced apoptosis. PMID:22202237

Hirahara, Noriyuki; Edamatsu, Takeo; Fujieda, Ayako; Fujioka, Masaki; Wada, Tsutomu; Tanaka, Tsuneo

2011-11-01

253

Chemotherapy induces tumor clearance independent of apoptosis  

PubMed Central

Dysregulation of apoptosis is associated with the development of human cancer and resistance to anti-cancer therapy. The ultimate goal of cancer treatment is to selectively induce cancer cell death and overcome drug resistance. A deeper understanding of how a given chemotherapy affects tumor cell death is needed to develop strategically designed anti-cancer agents. Here we utilize a xenograft mouse tumor system generated from genetically defined cells deficient in apoptosis to examine the involvement of multiple forms of cell death induced by cyclophosphamide (CP), a DNA alkylating agent commonly used in chemotherapy. We find that while apoptosis facilitates tumor regression, it is dispensable for complete tumor regression as other forms of cell death are activated. Sporadic necrosis is observed in both apoptosis-competent and deficient tumors evident by tumor cell morphology, extracellular release of high mobility group protein B1 (HMGB1), and activation of innate immune cells in CP treated tumors. Our findings indicate that in apoptosis-deficient tumors, necrosis may play a fundamental role in tumor clearance by stimulating the innate immune response. PMID:19047135

Guerriero, Jennifer L.; Ditsworth, Dara; Fan, Yongjun; Zhao, Fangping; Crawford, Howard C.; Zong, Wei-Xing

2008-01-01

254

Apoptosis signaling pathways and lymphocyte homeostasis.  

PubMed

It has been almost three decades since the term "apoptosis" was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways of apoptotic cell death induction: extrinsic signaling through death receptors that leads to the formation of the death-inducing signaling complex (DISC), and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations. PMID:17576411

Xu, Guangwu; Shi, Yufang

2007-09-01

255

Targeting the Apoptosis Pathway in Hematologic Malignancies  

PubMed Central

Apoptosis is a cell death program that is well-orchestrated for normal tissue homeostasis and for removal of damaged, old, or infected cells. It is regulated by intrinsic and extrinsic pathways. The intrinsic pathway responds to signals such as ultraviolet radiation or DNA damage and activates “executioner” caspases through a mitochondria-dependent pathway. The extrinsic pathway is activated by death signals induced, for example, by an infection that activates the immune system or receptor-mediated pathways. The extrinsic pathway signals also cascade down to executioner caspases that cleave target proteins and lead to cell death. Strict control of cellular apoptosis is important for the hematopoietic system as it has a high turnover rate. However, the apoptosis program is often deregulated in hematologic malignancies leading to the accumulation of malignant cells. Therefore, apoptosis pathways have been identified for development of anticancer therapeutics. We review here the proteins that have been targeted for anticancer drug development in hematologic malignancies. These include BCL-2 family proteins, death ligands and receptors, inhibitor of apoptosis family proteins, and caspases. Except for caspase activators, drugs that target each of these classes of proteins have advanced into clinical trials. PMID:24295132

Zaman, Shadia; Wang, Rui; Gandhi, Varsha

2014-01-01

256

Apoptosis drives cancer cells proliferate and metastasize  

PubMed Central

Cancer has been considered to be the result of accumulated gene mutations, which result in uncontrolled cell proliferations for a long time. Cancers are also regarded to be capable of immune evasion. Furthermore, resistance to apoptosis was recognized as an important trait of cancer in the last score of years. However, there are numerous paradoxical issues in this whole set of theory. For example, there is no known set of genes of which mutations are responsible for human cancers. As for the trait of ‘resistance to apoptosis’, the fact is that cancer has increased frequency of apoptosis. The more malignant the tumour is, the more apoptosis shows. In this study, we propose a new theory that apoptosis plays a key role in the malignant progression and metastasis of cancer. The growth of tumour is the difference between tumour cell proliferation and attrition plus the hyperplastic growth of stroma. Increased and unpreventable death caused by innate or environmental factors such as ischaemia and inflammation drives the tumour cells to proliferate relentlessly, move to new lands to establish colonies. In short, increased cell death is the origin of malignancy. PMID:23305095

Wang, Rui-An; Li, Qin-Long; Li, Zeng-Shan; Zheng, Ping-Ju; Zhang, Hui-Zhong; Huang, Xiao-Feng; Chi, Su-Min; Yang, An-Gang; Cui, Rutao

2013-01-01

257

Evaluation of apoptosis in immunotoxicity testing.  

PubMed

Immunotoxicity testing is important in determining the toxic effects of chemical substances, medicinal products, airborne pollutants, cosmetics, medical devices, and food additives. The immune system of the host is a direct target of these toxicants, and the adverse effects include serious health complications such as susceptibility to infections, cancer, allergic reactions, and autoimmune diseases. One way to investigate the harmful effects of different chemicals is to study apoptosis in immune cell populations. Apoptosis is defined as the programmed cell death, and in general, this process helps in development and maintains homeostasis. However, in the case of an insult by a toxicant, apoptosis of the immune cells can lead to immunosuppression resulting in the development of cancer and the inability to fight infections. Apoptosis is characterized by cell shrinkage, nuclear condensation, changes in cell membrane and mitochondria, DNA fragmentation into 200 base oligomers, and protein degradation by caspases. Various methods are employed in order to investigate apoptosis. These methods include direct measurement of apoptotic cells with flow cytometry and in situ labeling, as well as RNA, DNA, and protein assays that are indicative of apoptotic molecules. PMID:19967519

Nagarkatti, Mitzi; Rieder, Sadiye Amcaoglu; Vakharia, Dilip; Nagarkatti, Prakash S

2010-01-01

258

Sodium nitroprusside induces apoptosis of rabbit chondrocytes  

NASA Astrophysics Data System (ADS)

Osteoarthritis (OA) is characterized by a slowly progressing degradation of the matrix and destruction of articular cartilage. Apoptosis of chondrocyte is accounted for the mechanism of OA. Nitric oxide (NO), as a stimulus, has been shown to induce chondrocyte apoptosis by activating the matrix metalloproteinases (MMPs), increasing the expression of cyclooxygenase 2 (COX-2) and the level of prostaglandin E2 (PGE2), inhibiting the proteoglycan synthesis and type II collagen expression. In this study, sodium nitroprusside (SNP) was administered to be the NO donor to explore the mechanism of NO-induced apoptosis of rabbit chondrocytes obtained from six weeks old New Zealand rabbits. CCK-8 assay revealed the inhibitory effect of SNP on cell viability. We used flow cytometry (FCM) to assess the form of cell death by Annexin-V/propidium iodide (PI) double staining, and evaluate the change of mitochondrial membrane potential (??m). We found that the SNP induced chondrocyte apoptosis in a dose- and time-dependent manner and an observable reduction of ??m. In conclusion, our findings indicate that SNP induces apoptosis of rabbit chondrocytes via a mitochondria-mediated pathway.

Liang, Qian; Wang, Xiao-Ping; Chen, Tong-Sheng

2013-02-01

259

Real-Time Data Management, IP Telemetry, Data Integration, and Data Center Operations for the Source Physics Experiment (SPE), Nevada National Security Site  

NASA Astrophysics Data System (ADS)

The Nevada Seismological Laboratory (NSL) manages time-series data and high-throughput IP telemetry for the National Center for Nuclear Security (NCNS) Source Physics Experiment (SPE), underway on the Nevada National Security Site (NNSS). During active-source experiments, SPE's heterogeneous systems record over 350 channels of a variety of data types including seismic, infrasound, acoustic, and electro-magnetic. During the interim periods, broadband and short period instruments record approximately 200 channels of continuous, high-sample-rate seismic data. Frequent changes in sensor and station configurations create a challenging meta-data environment. Meta-data account for complete operational histories, including sensor types, serial numbers, gains, sample rates, orientations, instrument responses, data-logger types etc. To date, these catalogue 217 stations, over 40 different sensor types, and over 1000 unique recording configurations (epochs). Facilities for processing, backup, and distribution of time-series data currently span four Linux servers, 60Tb of disk capacity, and two data centers. Bandwidth, physical security, and redundant power and cooling systems for acquisition, processing, and backup servers are provided by NSL's Reno data center. The Nevada System of Higher Education (NSHE) System Computer Services (SCS) in Las Vegas provides similar facilities for the distribution server. NSL staff handle setup, maintenance, and security of all data management systems. SPE PIs have remote access to meta-data, raw data, and CSS3.0 compilations, via SSL-based transfers such as rsync or secure-copy, as well as shell access for data browsing and limited processing. Meta-data are continuously updated and posted on the Las Vegas distribution server as station histories are better understood and errors are corrected. Raw time series and refined CSS3.0 data compilations with standardized formats are transferred to the Las Vegas data server as available. For better data availability and station monitoring, SPE is beginning to leverage NSL's wide-area digital IP network with nine SPE stations and six Rock Valley area stations that stream continuous recordings in real time to the NSL Reno data center. These stations, in addition to eight regional legacy stations supported by National Security Technologies (NSTec), are integrated with NSL's regional monitoring network and constrain a high-quality local earthquake catalog for NNSS. The telemetered stations provide critical capabilities for SPE, and infrastructure for earthquake response on NNSS as well as southern Nevada and the Las Vegas area.

Plank, G.; Slater, D.; Torrisi, J.; Presser, R.; Williams, M.; Smith, K. D.

2012-12-01

260

Lipid Metabolism, Apoptosis and Cancer Therapy  

PubMed Central

Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy. PMID:25561239

Huang, Chunfa; Freter, Carl

2015-01-01

261

Apoptosis and Cytokines in Nonalcoholic Steatohepatitis  

PubMed Central

Nonalcoholic fatty liver disease (NAFLD) is one of the commonest causes of chronic liver disease in the United States, and represents several overlapping clinicopathological states, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although dysregulated lipid accumulation occurs across the spectrum of NAFLD, features of liver cell injury such as hepatocyte ballooning, cytoskeletal changes (Mallory-Denk bodies) and hepatocyte apoptosis occur predominantly in NASH, and distinguish NASH from simple steatosis. Indeed, NASH is a more serious form of liver damage, as cirrhosis and / or hepatocellular carcinoma are potential outcomes of NASH, but rarely occurs in individuals with simple steatosis. Hepatic injury and apoptosis that occur in adults is often dysregulated and is accompanied by the accumulation of immune cells, which produce cytokines and growth factors that drives chronic inflammation and may result in fibrosis. The purpose of this review is to summarize the process of apoptosis and roles of putative cytokines in progressive NAFLD. PMID:19818305

Syn, Wing-Kin; Choi, Steve S; Diehl, Anna Mae

2009-01-01

262

Targeted Overexpression of the Angiogenesis Inhibitor Thrombospondin1 in the Epidermis of Transgenic Mice Prevents Ultraviolet-B-Induced Angiogenesis and Cutaneous Photo-Damage  

Microsoft Academic Search

Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia, degradation of extracellular matrix molecules, and formation of wrinkles. To characterize the biologic role of the vascular system in the mediation of ultraviolet-B-induced skin damage, we performed quantitative analyses of cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin vascularization was greatly increased after chronic ultraviolet-B exposure

Kiichiro Yano; Hajimu Oura; Michael Detmar

2002-01-01

263

NF-?B Inducing Kinase, NIK Mediates Cigarette Smoke\\/TNF?-Induced Histone Acetylation and Inflammation through Differential Activation of IKKs  

Microsoft Academic Search

BackgroundNuclear factor (NF)-?B inducing kinase (NIK) is a central player in the non-canonical NF ?B pathway, which phosphorylates I?B kinase ? (IKK?) resulting in enhancement of target gene expression. We have recently shown that IKK? responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-?B activation. However,

Sangwoon Chung; Isaac K. Sundar; Jae-Woong Hwang; Fiona E. Yull; Timothy S. Blackwell; Vuokko L. Kinnula; Michael Bulger; Hongwei Yao; Irfan Rahman

2011-01-01

264

Ultraviolet-B-Induced G1 Arrest is Mediated by Downregulation of Cyclin-Dependent Kinase 4 in Transformed Keratinocytes Lacking Functional p53  

Microsoft Academic Search

In order to identify potential novel targets for ultraviolet-B-induced skin tumorigenesis, we assessed the effect of ultraviolet-B exposure on cell cycle progression of transformed keratinocytes with mutant p53. We show that ultraviolet-B exposure of human epidermoid carcinoma A431 cells results in G1 cell cycle arrest in both asynchronously growing and synchronized cells. A significant increase in G1 cell population was

Arianna L. Kim; Mohammad Athar; David R. Bickers; Jean Gautier

2002-01-01

265

T Cell Apoptosis in Human Heart Allografts  

PubMed Central

It is unclear whether the intracardial immune reactivity after heart transplantation influences the peripheral immunological status (activation or nonresponsiveness) of the patient. Co-stimulation and activation-induced cell death (AICD) or apoptosis play an important role in determining the balance between lymphocyte reactivity and nonreactivity. Therefore, we studied the expression of co-stimulatory molecules and the process of apoptosis in biopsies of human heart allografts, using immunohistochemistry. Although a normal expression of co-stimulatory molecules on antigen-presenting cells was observed, the expression of their counter-structures on T cells was absent. This may be due to chronic T cell activation, which can lead to the induction of apoptosis via the Fas/Fas ligand pathway. In the infiltrates, a considerable percentage of the lymphocytes, but not the macrophages, were apoptotic. Apoptosis was confirmed by DNA fragmentation analysis. Increased numbers of Bax-expressing versus decreased numbers of Bcl2-expressing lymphocytes in comparison with normal lymphoid tissue confirmed a imbalance in favor of apoptosis. Apoptosis was biased towards CD4+ T cells (65.7% versus 26.6% in CD8+ T cells). Fas was expressed on most of the infiltrating cells. Fas ligand expression was also observed, not only on most of the T cells but also on all macrophages. Because macrophages were often detected in close contact with T cells, they may play a role in T cell regulation via the Fas/Fas ligand pathway. This study indicates that, during rejection, not only is tissue damage induced by infiltrating T cells, but also the infiltrating lymphocytes themselves are actively down-regulated (eg, AICD) by one another and by macrophages in the infiltrate. This regulatory process may affect the immunological status of the patient after heart transplantation. PMID:9846972

Van Hoffen, Els; Van Wichen, Dick F.; Leemans, Jaklien C.; Broekhuizen, Richard A.J.F.; Bruggink, Annette H.; De Boer, Mark; De Jonge, Nicolaas; Kirkels, Hans; Slootweg, Piet J.; Gmelig-Meyling, Frits H.J.; De Weger, Roel A.

1998-01-01

266

Apoptosis and Necrosis in the Liver  

PubMed Central

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

267

Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during Apoptosis  

E-print Network

Immunity Article Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during Apoptosis mitochondrial dysfunc- tion and apoptosis, resulting in release of oxidized mitochondrial DNA (mtDNA regulated mitochondrial dysfunction and NLRP3 inflamma- some activation. Mitochondrial DNA directly induced

268

Inflammation & apoptosis in spinal cord injury  

PubMed Central

Spinal cord injury (SCI) consists of a two-steps process involving a primary mechanical injury followed by an inflammatory process and apoptosis. Secondary insult is characterized by further destruction of neuronal and glial cells, and leads to expansion of the damage, so that the paralysis can extend to higher segments. With the identification of mechanisms that either promote or prevent neuronal inflammation and apoptosis come new approaches for preventing and treating neurodegenerative disorders. From a clinical perspective, this article discusses novel targets for the development of therapeutic agents that have the potential to protect the spinal cord from irreversible damage and promote functional recovery. PMID:22561613

Zhang, Ning; Yin, Ying; Xu, Sheng-Jie; Wu, Yong-Ping; Chen, Wei-Shan

2012-01-01

269

Apoptosis and predisposition to oral cancer.  

PubMed

The term apoptosis, also known as programmed cell death (PCD), was coined by developmental biologists a number of years ago to describe a form of cell death characterized by several unique morphological and biochemical features. Genetic studies of the round worm Caeneorhabditis elegans, a simple multicellular organism, first revealed apoptosis to be an integral part of the developmental program. Subsequently, the importance of apoptosis in higher organisms was demonstrated in several eukaryotic systems. [n mammals, apoptosis is widespread during embryogenesis and in adult tissues. It is required for normal tissue homeostasis and for clonal selection in the immune system. In both developing and adult organisms, apoptosis plays a central role in reinforcing appropriate cellular patterns and in regulating cell number by eliminating cells that are harmful or no longer needed. It is becoming increasingly clear that disruption in the apoptosis pathway can contribute to the development of a number of developmental, inflammatory, degenerative, and neoplastic diseases. The effector arm of the apoptotic program includes members of the Bcl-2 gene family that function as either death agonists or death antagonists. These proteins participate in an elaborate genetically controlled biochemical pathway that functions to maintain tissue and organ homeostasis and serve as a critical defense mechanism to guard against malignant transformation. Cancer is the result of a series of genetic lesions that include activation of oncogenes and inactivation or loss of tumor suppressor genes. Several groups of investigators have observed that deregulated expression of oncogenes can subvert apoptotic pathways, resulting in prolonged cell survival. In pathological settings such as cancer, members of the Bcl-2 gene family are able to synergize with oncogenes and tumor suppressor genes to transform cells. In this review, we describe the process of apoptosis in mammalian cells and define the role and biochemical pathways through which the Bcl-2 gene family induce and/or protect cells from apoptosis. Last, we will discuss the evidence which suggests that alterations in this pathway may play a central role in tumorigenesis by allowing genetically damaged cells normally destined for elimination to persist, predisposing them to additional mutations and driving them to malignancy. PMID:10759418

Polverini, P J; Nör, J E

1999-01-01

270

APOPTOSIS: Mitochondria--the Death Signal Integrators  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Many of the intricate pathways of apoptosis that instruct a cell to kill itself involve the convergence of key proteins on the membranes of mitochondria. Such proteins induce the permeabilization of mitochondrial membranes and the release of caspase enzymes and nuclease activators that set in motion the final stages of programmed cell death. Now, as Brenner and Kroemer discuss in their Perspective, a proapoptotic transcription factor called TR3 has been found to move from its normal location in the nucleus to the mitochondria and to promote release of cytochrome c, a key event in apoptosis (Li et al.)

Catherine Brenner (Institut Gustave Roussy; Université de Technologie de Compiègne; Apoptosis, Cancer and Immunity Laboratory associated with the National League Against Cancer)

2000-08-18

271

APOPTOSIS: Till Death Us Do Part  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Epithelial cells need to remain firmly attached to each other and to the extracellular matrix. In the event that these cells become detached, they undergo apoptosis. In a Perspective, Hunt and Evan discuss new work that identifies the trigger that sets in motion the apoptosis program following detachment (Puthalakath et al.). The trigger turns out to be the pro-apoptotic protein Bmf. This protein is attached to the myosin V motor complex of the actin cytoskeleton under normal conditions, but is set free once cells become detached.

Abigail Hunt (University of California-San Francisco Cancer Center; )

2001-09-07

272

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.  

PubMed

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. PMID:23818305

Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

2013-09-01

273

A rapid SPE-based analytical method for UPLC/MS/MS determination of aminoglycoside antibiotic residues in bovine milk, muscle, and kidney.  

PubMed

An SPE-based cleanup protocol was developed for ultra-performance LC (UPLC)/MS/MS determination of residues of the common aminoglycoside antibiotics streptomycin, dihydrostreptomycin, neomycin, and gentamicin in bovine milk, kidney, and muscle. Recoveries for all compounds except neomycin ranged from 80 to 104% for all matrixes studied; recoveries for neomycin ranged from 71 to 84%. Intraday and interday precision data were under 15% for all sample matrixes. Compared with other recently reported cleanup methods, less sample is required, the use of potentially dangerous reagents is minimized, and fewer manipulations are required by the analyst. A high throughput 96-well plate format was used for SPE cleanup and UPLC/MS analysis. PMID:25632452

Young, Michael S; van Tran, Kim; Goh, Evelyn; Shia, Jeremy C

2014-01-01

274

Quantitative analysis of six polyynes and one polyene in Oplopanax horridus and Oplopanax elatus by pressurized liquid extraction and on-line SPE-HPLC.  

PubMed

A pressurized liquid extraction and on-line SPE-HPLC method was developed for simultaneous determination of six polyynes, including falcarindiol, oplopandiol, (11S,16S,9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate, oplopandiol acetate, oplopantriol A, oplopantriol B, and one polyene, (S,E)-nerolidol, in Oplopanax horridus and Oplpanax elatus. The analysis was conducted on a Grace Prevail C(18) column (3 microm, 7 mm x 33 mm) with gradient elution of acetonitrile and water after the sample loaded and washed with 42%ACN in 0.3 min on a phenomenex Strata-X on-line Extraction Cartridge SPE column (2.5 microm, 2.0 x 20 mm). All calibration curves of seven analytes showed good linearity within the test ranges. The validated method was successfully applied to quantify six polyynes and one polyene in two species of Oplopanax, O. horridus and O. elatus. PMID:20638214

Huang, Weihua; Yang, Jing; Zhao, Jing; Wang, Chong-zhi; Yuan, Chun-su; Li, Shao-ping

2010-12-01

275

Apoptosis and extracellular matrix–cell interactions in kidney disease  

Microsoft Academic Search

Apoptosis and extracellular matrix–cell interactions in kidney disease. Extracellular matrix (ECM)–cell interactions have major effects on phenotypic features such as cell growth, differentiation, and gene expression. Apoptosis is an active form of cell death that is crucial for maintaining an appropriate number of cells as well as tissue organization. Recent reports have implied that ECM can influence survival and apoptosis

Hirofumi Makino; Hitoshi Sugiyama; Naoki Kashihara

2000-01-01

276

Apoptosis induced by tea polyphenols in HL60 cells  

Microsoft Academic Search

In order to search for tumor cells apoptosis inducer, the apoptosis effects and mechanism of tea polyphenols were studied. Tea polyphenols are active compounds purified from tea. The apoptosis effects of tea polyphenols were observed on the human promyelocytic leukemic cells (HL-60) by an MTT reduction test, DNA agarose gel electrophoresis and a transmission electronic microscopy technique. After HL-60 cells

Yan Zhao; Jin Cao; Hong Ma; Jianwei Liu

1997-01-01

277

Oxygen Stress: A Regulator of Apoptosis in Yeast  

Microsoft Academic Search

Oxygen radicals are important components of metazoan apoptosis. We have found that apoptosis can be induced in the yeast Saccharomyces cerevisiae by depletion of glutathione or by low external doses of H 2 O 2 . Cycloheximide prevents apoptotic death reveal- ing active participation of the cell. Yeast can also be triggered into apoptosis by a mutation in CDC48 or

Frank Madeo; Eleonore Fröhlich; Martin Ligr; Martin Grey; Stephan J. Sigrist; Dieter H. Wolf; Kai-Uwe Fröhlich

1999-01-01

278

Executionary pathway for apoptosis: lessons from mutant mice  

Microsoft Academic Search

Apoptosis or programmed cell death (PCD) is an evolutionarily conserved cellular process that is essential for normal development and homeostasis of multicellular organisms. Defects in the apoptosis signaling result in many diseases including autoimmune diseases and cancer. The apoptosis signaling pathway was first described genetically in the nematode Caenorhabditis elegans which serves as a framework for the more complex apoptotic

Minna WOO; Razqallah HAKEM; Tak W MAK

2000-01-01

279

Versatile online SPE-HPLC method for the analysis of Irinotecan and its clinically relevant metabolites in biomaterials.  

PubMed

Monitoring levels of Irinotecan and its metabolites during cancer therapy could help link broad interpatient variations in antitumor activity and toxicity to the patient's metabolic status. We have developed and validated a versatile and highly sensitive method for the simultaneous determination of Irinotecan and its clinically relevant metabolites 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide. Sample clean-up involves precipitation by acetone/methanol/0.5 M trichloroacetic acid at 4:4:2 v/v followed by extraction of the metabolites on an SPE column by 20% methanol in 25 mM KH2 PO4 pH 2.9. Online transfer to an analytical ?Bondapak C18 column, elution with 24% acetonitrile (ACN) in 0.1 M KH2 PO4 pH 2.9 and fluorescence detection with excitation at 375 nm and emission at 430 nm for SN-38 glucuronide and Irinotecan or 540 nm for SN-38 results in high sensitivity (1-2 pg) and short (?10 min) run times. The method was used to determine the degree of SN-38 glucuronidation in mice after Irinotecan administration and in cultured cancer cells exposed to SN-38. The method may be used to better understand Irinotecan metabolism, personalize therapy, and develop Irinotecan-based tumor targeting therapies. PMID:24339241

Prijovich, Zeljko M; Burnouf, Pierre-Alain; Roffler, Steve R

2014-02-01

280

The Simultaneous Determination of Six Flame Retardants in Water Samples Using SPE Pre-concentration and UHPLC-UV Method.  

PubMed

Analytical method for the determination of six flame retardants (FRs) from two groups was proposed. These groups included the brominated flame retardants (BFRs) 3,3',5,5'-tetrabromobisphenol A (TBBPA), 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and tetrabromophthalic anhydride (TBPA) and triester organophosphate flame retardants (OPFRs) tris(2,3-dibromopropyl) phosphate (TBPP), ethylhexyl diphenyl phosphate (EHDP) and triphenyl phosphate (TPhP). Reversed phase ultrahigh-performance liquid chromatography (UHPLC) with a UV detector, different chromatographic columns, different mobile phases and gradient elution programmes were used to obtain the best separations within the shortest possible time. Solid-phase extraction (SPE) was examined as a pre-concentration step from distilled water. The column with the highest recoveries (the Bond Elut ENV column gave recoveries over 70 % for all compounds) was then tested on 1-L blank surface water samples. The proposed analytical procedure was applied for the determination of FRs in surface water samples. The concentrations of FRs found in water samples ranged from 0.03 (TPhP) to 3.10 ?g L(-1) (HBCD). Method detection limits (MDLs) ranged from 0.008 to 0.518 ?g L(-1), and method quantification limits (MQLs) ranged from 0.023 to 1.555 ?g L(-1) for all compounds. PMID:24672141

Kowalski, Bartosz; Mazur, Maciej

2014-01-01

281

Phytochemical profile of aerial parts and roots of Wachendorfia thyrsiflora L. studied by LC-DAD-SPE-NMR.  

PubMed

Hyphenated liquid chromatography - diode array detection - solid phase extraction - nuclear magnetic resonance spectroscopy (LC-DAD-SPE-NMR) was used to investigate the phytochemical composition of aerial parts and roots of Wachendorfia thyrsiflora (Haemodoraceae). Eleven phenylphenalenones and related compounds were identified in the aerial parts of the plant, ten compounds were found in the roots, and four additional compounds occurred in both plant parts. Twelve compounds are previously unreported natural products including five alkaloids (phenylbenzoisoquinolinones) are described here for the first time. In the work presented here, phenylphenalenones with an intact C(19) core structure were found only in the roots. Oxa analogs with a C(18)O scaffold occurred both in the roots and in the aerial plant parts, while most of the aza analogs with a C(18)N scaffold were detected in the aerial plant parts. This distribution pattern suggests that phenylphenalenones form in the roots, then the intact C(19) skeleton is converted into oxa analogs in the roots, translocated into the leaves and further reacted with amines or amino acids to form aza analogs (phenylbenzoisoquinolin-1,6-dione alkaloids). PMID:22717508

Fang, Jingjing; Kai, Marco; Schneider, Bernd

2012-09-01

282

Detailed Comparison of Observed Dose-Time Profile of October 19-20, 1989 SPE on Mir with Model Calculations  

NASA Technical Reports Server (NTRS)

The dose rate dynamics of the October 19-20,1989 solar energetic particle (SPE) event as observed by the Liulin instrument onboard the Mir orbital station was analyzed in light of new calculations of the geomagnetic cutoff and improved estimates of the less than 100 MeV energy spectra from the GOES satellite instrument. The new calculations were performed using the as-flown Mir orbital trajectory and includes time variations of the cutoff rigidity due to changes in the kappa (sub p) index. Although the agreement of total event integrated calculated dose to the measured dose is good, it results from some measured dose-time profile been higher and some lower than model calculations. They point to the need to include the diurnal variation of the geomagnetic cutoff and modifications of the cutoffs to variations in kappa (sub p) in model calculations. Understanding of such events in light of the upcoming construction of the International Space Station during the period of maximum solar activity needs to be vigorously pursued.

Badhwar, Gautam D.; Atwell, William

1999-01-01

283

Near-Infrared Spectral Monitoring of Triton with IRTF/SpeX II: Spatial Distribution and Evolution of Ices  

E-print Network

This report arises from an ongoing program to monitor Neptune's largest moon Triton spectroscopically in the 0.8 to 2.4 micron range using IRTF/SpeX. Our objective is to search for changes on Triton's surface as witnessed by changes in the infrared absorption bands of its surface ices N2, CH4, H2O, CO, and CO2. We have recorded infrared spectra of Triton on 53 nights over the ten apparitions from 2000 through 2009. The data generally confirm our previously reported diurnal spectral variations of the ice absorption bands (Grundy & Young 2004). Nitrogen ice shows a large amplitude variation, with much stronger absorption on Triton's Neptune-facing hemisphere. We present evidence for seasonal evolution of Triton's N2 ice: the 2.15 micron absorption band appears to be diminishing, especially on the Neptune-facing hemisphere. Although it is mostly dissolved in N2 ice, Triton's CH4 ice shows a very different longitudinal variation from the N2 ice, challenging assumptions of how the two ices behave. Unlike Trito...

Grundy, W M; Stansberry, J A; Buie, M W; Olkin, C B; Young, E F

2009-01-01

284

Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB processing and virulence.  

PubMed

Small cyclic nucleotide derivatives are employed as second messengers by both prokaryotes and eukaryotes to regulate diverse cellular processes responding to various signals. In bacteria, c-di-AMP has been discovered most recently, and some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide derivative as a second messenger instead of c-di-GMP, a well-studied important bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has not been examined yet. To test the cellular role of GdpP, we created a strain with a nonpolar inframe deletion of the gdpP gene, and examined the properties of the strain including virulence. From this study, we demonstrated that GdpP influences the biogenesis of SpeB, the major secreted cysteine protease, at a post-translational level, susceptibility to the beta lactam antibiotic ampicillin, and is necessary for full virulence in a murine subcutaneous infection model. PMID:23869242

Cho, Kyu Hong; Kang, Song Ok

2013-01-01

285

A ?-SPE procedure for the determination of cannabinoids and their metabolites in urine by LC-MS/MS.  

PubMed

In this paper the development and validation of a method for the analysis of THC-COOH, THC, THC-OH, CBD and CBN in their total form in urine by LC-MS/MS is presented. Tandem hydrolysis, i.e. enzymatic and basic, has been found optimal for the simultaneous analysis of the selected analytes in urine: basic hydrolysis is more effective for the cleavage of THC-COOH glucuronide while enzymatic hydrolysis allows the cleavage of the conjugated cannabinoids possessing ether bonds (THC, THC-OH, CBD). The whole procedure requires a 2h enzymatic hydrolysis using only 90?L of urine by ?-SPE extraction technique with C18 tips. Clear advantages in terms of time and of enzyme reduction are obtained and the cost of the analysis can be dramatically reduced. Satisfactory recovery values and matrix effect are obtained, and the chromatographic run, performed with a fused-core column, allowed the complete analyte separation in only 3min (total run 5.8min) with a common HPLC system. Furthermore the whole procedure has been validated according to SWGTOX guidelines: LOQs are between 6 and 10ppb, quite lower than the requested cut-off for urine testing; intermediate reproducibility of the selected analytes is below 10% and accuracy is between 85% and 113%, except for CBD, included only for semi-quantitative determination. PMID:24469020

Montesano, Camilla; Sergi, Manuel; Odoardi, Sara; Simeoni, Maria Chiara; Compagnone, Dario; Curini, Roberta

2014-03-01

286

Distributions of H 2O and CO 2 ices on Ariel, Umbriel, Titania, and Oberon from IRTF\\/SpeX observations  

Microsoft Academic Search

We present 0.8–2.4 ?m spectral observations of uranian satellites, obtained at IRTF\\/SpeX on 17 nights during 2001–2005. The spectra reveal for the first time the presence of CO2 ice on the surfaces of Umbriel and Titania, by means of 3 narrow absorption bands near 2 ?m. Several additional, weaker CO2 ice absorptions have also been detected. No CO2 absorption is

W. M. Grundy; L. A. Young; J. R. Spencer; R. E. Johnson; E. F. Young; M. W. Buie

2006-01-01

287

An SPE-assisted BODIPY fluorometric paper sensor for the highly selective and sensitive determination of Cd²? in complex sample: rice.  

PubMed

By using sensing technology, the individual component analysis at trace level in complex samples remains problematic simply because of various interfering species. For example, the determination of Cd(2+) in rice is difficult due to the co-existing interfering metal cations at thousands or even millions of times higher concentrations. In this study, a heavy-metal ion sensitive BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-based fluorometric paper sensor with assistance of solid phase extraction (SPE) was developed for the highly selective and sensitive determination of trace Cd(2+) in rice. SPE column packed with prepared sulfonated PS-DVB microspheres was employed to enrich trace Cd(2+) and meanwhile remove most interfering heavy-metal ions in simulated complex rice sample with oxalic acid as eluent, which was theoretically selected on the basis of f values. Mn(2+), as a major coexistent heavy-metal ion, could not be easily removed by SPE, but showed little fluorescent response for BODIPY fluorometric paper sensor even in excess amounts. Combining the separation and enrichment capability of SPE column with the selectivity of BODIPY-based fluorometric paper sensor, we were able to detect trace Cd(2+) in complex samples. The response of fluorometric paper sensor was linearly related with Cd(2+) concentrations in the range of 0.5-4 ?M, with a detection limit of 0.5 ?M. Twelve real rice samples spiked with Cd(2+) were analysed using this method and the results are in good agreement with ICP-MS measurements. PMID:24802241

Zhang, Yu; Li, Hui; Niu, Li-Ya; Yang, Qing-Zheng; Guan, Ya-Feng; Feng, Liang

2014-06-21

288

Determination of polychlorinated biphenyls and organochlorine pesticides in small volumes of human blood by high-throughput on-line SPE-LVI-GC-HRMS.  

PubMed

A fully automated and robust method featuring on-line solid-phase extraction (SPE) and large volume injection (LVI) gas chromatographic (GC) high resolution mass spectrometry (HRMS) is used to determine polychlorinated biphenyls (PCBs) and organochlorine pesticides, such as penta- and hexachlorobenzene (PeCBz, HxCBz), hexachlorocyclohexane isomers (HCH) and 4,4'-dichlorodiphenyldichloroethene (a metabolite of dichlorodiphenyltrichloroethane (DDT)), with only 200?l of human blood, serum or plasma. After spiking the sample with (13)C-labeled internal standards and precipitating the proteins, the sample is passed through a 10mm×2.0mm ID SPE cartridge filled with C18 material that adsorbs the analytes. After washing and drying, the cartridge is extracted with hexane/dodecane (99/1, v/v); the extract is directly injected into a LVI where GC/HRMS analysis follows. The fully automated system utilizes a robotic autosampler and a modular SPE system including two high-pressure syringe pumps, an automatic SPE cartridge exchanger unit and 6 switchable valves. All sample preparation steps are performed within 20min during the GC run of a previous sample, limiting the throughput with only the GC runtime. The contents are quantified using the isotope dilution method. Due to laboratory air contamination problems, we achieved LOQs of 0.017 (PeCBz), 0.009 (HxCBz), 0.007 (HCH), 0.016 (DDE), while for the six indicator PCBs, we achieved values of 0.030 (PCB-28), 0.044 (PCB-52), 0.024 (PCB-101), 0.009 (PCB-138), 0.015 (PCB-153) and 0.008 (PCB-180)?g/l serum. Under clean laboratory air conditions, these values may be improved. This method is recommended when high throughput is desirable and/or only small amounts of material are available, such as during studies involving children. PMID:24361859

Wittsiepe, Jürgen; Nestola, Marco; Kohne, Matthias; Zinn, Peter; Wilhelm, Michael

2014-01-15

289

From the Cover: Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: An integrin-binding cysteine protease  

Microsoft Academic Search

Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor

Todd F. Kagawa; Jakki C. Cooney; Heather M. Baker; Sean McSweeney; Mengyao Liu; Siddeswar Gubba; James M. Musser; Edward N. Baker

2000-01-01

290

SPE–TLC Profiling of Impurities in 1-(3,4-Methylenedioxyphenyl)-2-nitropropene, an Intermediate in 3,4-Methylenedioxy- methamphetamine (MDMA) Synthesis  

Microsoft Academic Search

Impurity profiling of 1–(3,4-methylenedioxyphenyl)-2-nitropropene, an intermediate in the synthesis of 3,4-methylenedioxymethamphetamine (MDMA), has been studied by SPE combined with TLC. Extraction of impurities was performed on C 18columns. TLC separation was performed on 0.2 mm silica gel 60 plates, with fluorescent indicator F 254, in a horizontal developing chamber. To improve the quality of the profile (increase the TLC sensitivity)

J. Kochana; J. Wilamowski; A. Parczewski

2004-01-01

291

Bulk Segregant Analysis Followed by High-Throughput Sequencing Reveals the Neurospora Cell Cycle Gene, ndc-1, To Be Allelic with the Gene for Ornithine Decarboxylase, spe-1 ? †  

PubMed Central

With the advent of high-throughput DNA sequencing, it is now straightforward and inexpensive to generate high-density small nucleotide polymorphism (SNP) maps. Here we combined high-throughput sequencing with bulk segregant analysis to expedite mutation mapping. The general map location of a mutation can be identified by a single backcross to a strain enriched in SNPs compared to a standard wild-type strain. Bulk segregant analysis simultaneously increases the likelihood of determining the precise nature of the mutation. We present here a high-density SNP map between Neurospora crassa Mauriceville-1-c (FGSC2225) and OR74A (FGSC2489), the strains most typically used by Neurospora researchers to carry out mapping crosses. We further have demonstrated the utility of the Mauriceville sequence and our approach by mapping the mutation responsible for the only existing temperature-sensitive (ts) cell cycle mutation in Neurospora, nuclear division cycle-1 (ndc-1). The single T-to-C point mutation maps to the gene encoding ornithine decarboxylase (ODC), spe-1 (NCU01271), and changes a Phe to a Ser residue within a highly conserved motif next to the catalytic site of the enzyme. By growth on spermidine and complementation with a wild-type spe-1 gene, we showed that the defect in spe-1 is responsible for the ts ndc-1 mutation. Based on our results, we propose changing ndc-1 to spe-1ndc, which reflects that this mutation results in an ODC with a specific nuclear division defect. PMID:21515825

Pomraning, Kyle R.; Smith, Kristina M.; Freitag, Michael

2011-01-01

292

Application of Colorimetric Solid Phase Extraction (C-SPE) to Monitoring Nickel(II) and Lead(II) in Spacecraft Water Supplies  

NASA Technical Reports Server (NTRS)

Archived water samples collected on the International Space Station (ISS) and returned to Earth for analysis have, in a few instances, contained trace levels of heavy metals. Building on our previous advances using Colorimetric Solid Phase Extraction (C-SPE) as a biocide monitoring technique, we are devising methods for the low level monitoring of nickel(II), lead(II) and other heavy metals. C-SPE is a sorption-spectrophotometric platform based on the extraction of analytes onto a membrane impregnated with a colorimetric reagent that are then quantified on the surface of the membrane using a diffuse reflectance spectrophotometer. Along these lines, we have determined nickel(II) via complexation with dimethylglyoxime (DMG) and begun to examine the analysis of lead(II) by its reaction with 2,5- dimercapto-1,3,4-thiadiazole (DMTD) and 4-(2- pyridylazo)-resorcinol (PAR). These developments are also extending a new variant of C-SPE in which immobilized reagents are being incorporated into this methodology in order to optimize sample reaction conditions and to introduce the colorimetric reagent. This paper describes the status of our development of these two new methods.

Diaz, Neil C.; Gazda, Daniel B.; Fritz, James S.; Porter, Marc D.; Rutz, Jeff; Mudgett, Paul; Schultz, John

2004-01-01

293

Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.  

PubMed

Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor form of SpeB at 1.6-A resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S. Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions. The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad. The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site. The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of S. pyogenes. PMID:10681429

Kagawa, T F; Cooney, J C; Baker, H M; McSweeney, S; Liu, M; Gubba, S; Musser, J M; Baker, E N

2000-02-29

294

Direct rapid analysis of multiple PPCPs in municipal wastewater using ultrahigh performance liquid chromatography-tandem mass spectrometry without SPE pre-concentration.  

PubMed

Ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was utilized to develop a rapid, sensitive and reliable method without solid phase extraction (SPE) pre-concentration for trace analysis of 11 pharmaceuticals and personal care products (PPCPs) in in?uent and ef?uent from municipal wastewater treatment plants (WWTPs). This method not only shortened the analysis time but also reduced analysis cost significantly by omitting SPE process and avoiding the consumption of SPE cartridge. Detection parameters for UHPLC-MS/MS analysis were optimized, including sample pH, eluent, mobile phase (solvent and additive), column temperature, and ?ow rate. Under the optimal conditions, all analytes were well separated and detected within 8.0min by UHPLC-MS/MS. The method quantification limits (MQLs) for the 11 PPCPs ranged from 0.040 to 88ngL(-1) and from 0.030 to 90ngL(-1) for influent and effluent, respectively. The matrix effect was systematically investigated and quantified for different types of samples. The analysis of in?uent and ef?uent samples of two WWTPs in Hong Kong revealed the presence of 11 PPCPs, including acyclovir, benzophenone-3, benzylparaben, carbamazepine, ethylparaben, fluconazole, fluoxetine, methylparaben, metronidazole, propylparaben, and ranitidine. Their concentrations ranged from 9.1 to 1810ngL(-1) in influent and from 6.5 to 823ngL(-1) in effluent samples collected from Hong Kong WWTPs. PMID:22790701

Yu, Ke; Li, Bing; Zhang, Tong

2012-08-13

295

Chronological aging leads to apoptosis in yeast  

Microsoft Academic Search

uring the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologi- cally aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is

Eva Herker; Helmut Jungwirth; Katharina A. Lehmann; Corinna Maldener; Kai-Uwe Fröhlich; Silke Wissing; Sabrina Büttner; Markus Fehr; Stephan Sigrist; Frank Madeo

2004-01-01

296

Chemotherapy Induces Tumor Clearance Independent of Apoptosis  

Microsoft Academic Search

Dysregulation of apoptosis is associated with the development of human cancer and resistance to anticancer therapy. The ultimate goal of cancer treatment is to selectively induce cancer cell death and overcome drug resistance. A deeper understanding of how a given chemotherapy affects tumor cell death is needed to develop strategically designed anticancer agents. Here, we use a xenograft mouse tumor

Jennifer L. Guerriero; Yongjun Fan; Fangping Zhao; Howard C. Crawford; Wei-Xing Zong

2008-01-01

297

Apoptosis in the developing visual system  

Microsoft Academic Search

Programed cellular death is a widespread phenomenon during development of the nervous system. Two classes of molecules are particularly important in the context of apoptosis control in the nervous system: intracellular effectors homologous to the Caenorhabditis elegans Ced-3, -4, and -9 proteins, which in mammals correspond to the proteases of the caspase family, Apaf-1, and the members of the Bcl-2

Alessandro Cellerino; Mathias Bähr; Stefan Isenmann

2000-01-01

298

Molecular mechanisms of caspase regulation during apoptosis  

Microsoft Academic Search

Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. Although general structural features are shared between the initiator and the effector caspases, their activation, inhibition and release of inhibition are differentially regulated. Biochemical and structural studies have led to important advances in understanding the underlying molecular mechanisms of caspase regulation. This article reviews

Stefan J. Riedl; Yigong Shi

2004-01-01

299

Inhibition of apoptosis by intracellular protozoan parasites  

Microsoft Academic Search

Protozoan parasites which reside inside a host cell avoid direct destruction by the immune system of the host. The infected cell, however, still has the capacity to counteract the invasive pathogen by initiating its own death, a process which is called programmed cell death or apoptosis. Apoptotic cells are recognised and phagocytosed by macrophages and the parasite is potentially eliminated

Volker T. Heussler; Peter Küenzi; Sven Rottenberg

2001-01-01

300

Apoptosis-based therapies and drug targets  

Microsoft Academic Search

The pathogenesis of many diseases is most closely connected with aberrantly regulated apoptotic cell death. The past 15 years have witnessed an explosion in the basic knowledge of mechanisms that regulate apoptosis and the mediators that either trigger or inhibit cell death. Consequently, great interest has emerged in devising therapeutic strategies for modulating the key molecules of life-and-death decisions. Numerous

U Fischer; K Schulze-Osthoff

2005-01-01

301

The modulation of apoptosis by oncogenic viruses  

PubMed Central

Transforming viruses can change a normal cell into a cancer cell during their normal life cycle. Persistent infections with these viruses have been recognized to cause some types of cancer. These viruses have been implicated in the modulation of various biological processes, such as proliferation, differentiation and apoptosis. The study of infections caused by oncogenic viruses had helped in our understanding of several mechanisms that regulate cell growth, as well as the molecular alterations leading to cancer. Therefore, transforming viruses provide models of study that have enabled the advances in cancer research. Viruses with transforming abilities, include different members of the Human Papillomavirus (HPV) family, Hepatitis C virus (HCV), Human T-cell Leukemia virus (HTLV-1), Epstein Barr virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). Apoptosis, or programmed cell death, is a tightly regulated process that plays an important role in development and homeostasis. Additionally, it functions as an antiviral defense mechanism. The deregulation of apoptosis has been implicated in the etiology of diverse diseases, including cancer. Oncogenic viruses employ different mechanisms to inhibit the apoptotic process, allowing the propagation of infected and damaged cells. During this process, some viral proteins are able to evade the immune system, while others can directly interact with the caspases involved in apoptotic signaling. In some instances, viral proteins can also promote apoptosis, which may be necessary for an accurate regulation of the initial stages of infection. PMID:23741982

2013-01-01

302

The modulation of apoptosis by oncogenic viruses.  

PubMed

Transforming viruses can change a normal cell into a cancer cell during their normal life cycle. Persistent infections with these viruses have been recognized to cause some types of cancer. These viruses have been implicated in the modulation of various biological processes, such as proliferation, differentiation and apoptosis. The study of infections caused by oncogenic viruses had helped in our understanding of several mechanisms that regulate cell growth, as well as the molecular alterations leading to cancer. Therefore, transforming viruses provide models of study that have enabled the advances in cancer research. Viruses with transforming abilities, include different members of the Human Papillomavirus (HPV) family, Hepatitis C virus (HCV), Human T-cell Leukemia virus (HTLV-1), Epstein Barr virus (EBV) and Kaposi's Sarcoma Herpesvirus (KSHV).Apoptosis, or programmed cell death, is a tightly regulated process that plays an important role in development and homeostasis. Additionally, it functions as an antiviral defense mechanism. The deregulation of apoptosis has been implicated in the etiology of diverse diseases, including cancer. Oncogenic viruses employ different mechanisms to inhibit the apoptotic process, allowing the propagation of infected and damaged cells. During this process, some viral proteins are able to evade the immune system, while others can directly interact with the caspases involved in apoptotic signaling. In some instances, viral proteins can also promote apoptosis, which may be necessary for an accurate regulation of the initial stages of infection. PMID:23741982

Fuentes-González, Alma Mariana; Contreras-Paredes, Adriana; Manzo-Merino, Joaquín; Lizano, Marcela

2013-01-01

303

Apoptosis: Programmed cell death in fetal development  

Microsoft Academic Search

Controlled death of cells is as much a part of embryonal development as is cell proliferation and differentiation. This cell suicide is controlled by cell genes involved in induction or prevention of programmed cell death (PCD). During embryogenesis PCD implicates cell elimination, necessary in fashioning of the body, moulding of tissues. PCD is often used synonymous with the designation apoptosis,

C. Haanen; I. Vermes

1996-01-01

304

Rho signals to cell growth and apoptosis  

Microsoft Academic Search

Ras and Rho GTPases are among the best studied signaling molecules in molecular biology. Essential cellular processes, such as cell growth, lipid metabolism, cytoarchitecture, membrane trafficking, transcriptional regulation, apoptosis, and response to genotoxic agents, are directly modulated by different members of this superfamily of proteins. Not until recently have we begun to understand the physiological implications of Ras and Rho

Salvador Aznar; Juan Carlos Lacal

2001-01-01

305

Immunology 102 at poxvirus U: Avoiding apoptosis  

Microsoft Academic Search

Poxviruses are large complex viruses that replicate in the cytoplasm of cells without integrating their DNA into the host genome or undergoing a latent intracellular stage. In addition to viral enzymes for DNA and RNA synthesis, poxviruses encode many proteins that modulate host responses. These include inhibitors of apoptosis induced by ligand binding to cell surface receptors, peroxides, ultraviolet light,

Joanna L. Shisler; Bernard Moss

2001-01-01

306

Measuring apoptosis in mammals in vivo.  

PubMed

Apoptosis is a mode of cell death that is essential in multicellular organisms for the removal of superfluous, damaged, or potentially dangerous cells during development, infection, or normal tissue homeostasis. To prevent inflammation, cells undergoing apoptosis produce "find-me" signals that trigger the recruitment of phagocytes, which clear the apoptotic cells on recognition of "eat-me" signals. Despite the loss of billions of cells per day by apoptosis in the human body, the number of apoptotic cells found in healthy tissue is surprisingly low and reflects the efficiency of this process. However, in certain conditions (e.g., in cancer cells responding to chemotherapy), the number of apoptotic cells is too high to be efficiently cleared by phagocytes, and apoptotic cells can be observed. In these situations, the detection of apoptosis may be helpful in monitoring disease progression as well as in predicting the responses of tumors to anticancer therapies. Here we introduce various methods for monitoring apoptotic cells in vivo using a murine model of B-cell lymphoma and a solid tumor xenograft. PMID:25368316

Newbold, Andrea; Martin, Ben P; Cullinane, Carleen; Bots, Michael

2014-11-01

307

Death penalty for keratinocytes: apoptosis versus cornification  

Microsoft Academic Search

Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a

S Lippens; G Denecker; P Ovaere; P Vandenabeele; W Declercq

2005-01-01

308

Involvement of Cellular Proteolytic Machinery in Apoptosis  

Microsoft Academic Search

Programmed cell death (PCD), a genetically controlled cell deletion process, plays an important role in the regulation of cellular and tissue homeostasis. The requisite for proteolysis during PCD-induced apoptosis is well documented. The cellular proteolytic machinery includes numerous proteases localized in membranes, cytoplasm, and nucleus. This machinery may function to remove denatured or misfolded protein from the cytoplasm on a

Boris Zhivotovsky; David H. Burgess; Daina M. Vanags; Sten Orrenius

1997-01-01

309

The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism.  

PubMed Central

The major mechanism of cytotoxic lymphocyte killing involves the directed release of granules containing perforin and a number of proteases onto the target cell membrane. One of these proteases, granzyme B, has an unusual substrate site preference for Asp residues, a property that it shares with members of the emerging interleukin-1beta-converting enzyme (ICE)/CED-3 family of proteases. Here we show that granzyme B is sufficient to reproduce rapidly all of the key features of apoptosis, including the degradation of several protein substrates, when introduced into Jurkat cell-free extracts. Granzyme B-induced apoptosis was neutralized by a tetrapeptide inhibitor of the ICE/CED-3 family protease, CPP32, whereas a similar inhibitor of ICE had no effect. Granzyme B was found to convert CPP32, but not ICE, to its active form by cleaving between the large and small subunits of the CPP32 proenzyme, resulting in removal of the prodomain via an autocatalytic step. The cowpox virus protein CrmA, a known inhibitor of ICE family proteases as well as granzyme B, inhibited granzyme B-mediated CPP32 processing and apoptosis. These data demonstrate that CPP32 activation is a key event during apoptosis initiated by granzyme B. Images PMID:8665848

Martin, S J; Amarante-Mendes, G P; Shi, L; Chuang, T H; Casiano, C A; O'Brien, G A; Fitzgerald, P; Tan, E M; Bokoch, G M; Greenberg, A H; Green, D R

1996-01-01

310

Courses: Nursing (NURS) Page 355Sonoma State University 2011-2012 Catalog nurS 312 bACCAlAureAte nurSinG perSpeCtiVeS i (4)  

E-print Network

Courses: Nursing (NURS) Page 355Sonoma State University 2011-2012 Catalog nurS 312 bACCAlAureAte nurSinG perSpeCtiVeS i (4) Explore contemporary perspectives in baccalaureate nursing with emphasis, leadership and professional development. nurS 313 bACCAlAureAte nurSinG perSpeCtiVeS ii (4) Seminar, 4 hours

Ravikumar, B.

311

Apoptosis-inducing protein derived from hepatocyte selectively induces apoptosis in lymphocytes  

PubMed Central

The liver is where lymphocytes undergo activation-induced cell death (AICD) at the resolution phase of an immune response, which is crucial for homeostasis of the immune system and prevention of autoimmunity. Exploring the machinery of AICD in the liver, we found that a primary culture supernatant of murine hepatocytes had an antiproliferative effect on antigen-stimulated T clone and T lymphoma cells. Biological study showed that the antiproliferation was due to induction of apoptosis in a caspase-dependent manner. The apoptosis-inducing potential was sensitive to trypsin, heat (> 70°) and acid (< pH 5) treatment but could not be neutralized by anti-tumour necrosis factor-?, anti-Fas ligand, or anti-transforming growth factor-? antibodies. Biochemical study of the isolated and purified apoptosis-inducing component from the supernatant showed that it was a protein with a molecular mass of about 68 000–70 000. It induced apoptotic change in murine T and B cells, and to a lesser degree, in human lymphoid cells, but not in macrophages. Biochemical and biological characteristics distinguish this protein from others that have been reported to induce apoptosis of lymphocytes. The identification of an apoptosis-inducing protein derived from murine hepatocytes, which selectively induces apoptosis in lymphocytes, suggests one possible mechanism for immune suppression in the liver. PMID:12519310

Ikeda, Masanobu; Yoshikawa, Hideshi; Liu, Jie; Nakajima, Yasuo; Akahane, Yoshihiro; Tasaka, Kachio

2003-01-01

312

[Delayed apoptosis and its regulation in astrocytes].  

PubMed

Astrocytes, the most abundant glial cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We found that reperfusion of cultured astrocytes after Ca2+ depletion causes Ca2+ overload followed by delayed cell death and the Na(+)-Ca2+ exchanger in the reverse mode is responsible for this Ca(2+)-mediated cell injury (Ca2+ paradox injury). The Ca2+ paradox injury of cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion injury, since a similar paradoxical change in extracellular Ca2+ concentration is reported in ischemic brain tissue. This review summarizes the mechanisms underlying the Ca(2+)-mediated injury of astrocytes and the protective effects of drugs against Ca2+ reperfusion injury. This study shows that Ca2+ reperfusion injury of astrocytes is accompanied by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species, calcineurin, caspase-3, and NF-kappa B are involved in Ca2+ reperfusion-induced delayed apoptosis of astrocytes. Several drugs including CV-2619, T-588 and ibudilast protect astrocytes against the delayed apoptosis. CV-2619 prevents astrocytes from the delayed apoptosis by production of nerve growth factor, resulting in an activation of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 (PI3) kinase signal pathways. The protective effect of T-588 is mainly mediated by an activation of MAP/ERK signal cascade. Moreover, ibudilast prevents the Ca2+ reperfusion-induced delayed apoptosis of astrocytes via cyclic GMP signaling pathway. Further studies in this system will contribute to the development of new drugs that attenuate ischemia/reperfusion injury via modulation of astrocytes. PMID:11558150

Takuma, K

2001-09-01

313

miR-30b, Down-Regulated in Gastric Cancer, Promotes Apoptosis and Suppresses Tumor Growth by Targeting Plasminogen Activator Inhibitor-1  

PubMed Central

Background Gastric cancer is one of the most common malignant diseases worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with tumor development and progression. Our previous studies have revealed that H. pylori infection was able to induce the altered expression of miR-30b in gastric epithelial cells. However, little is known about the potential role of miR-30b in gastric cancer. Methods We analyzed the expression of miR-30b in gastric cancer cell lines and human gastric cancer tissues. We examined the effect of miR-30b mimics on the apoptosis of gastric cancer cells in vitro by flow cytometry (FCM) and caspase-3/7 activity assays. Nude mouse xenograft model was used to determine whether miR-30b is involved in tumorigenesis of gastric cancer. The target of miR-30b was identified by bioinformatics analysis, luciferase assay and Western blot. Finally, we performed the correlation analysis between miR-30b and its target expression in gastric cancer. Results miR-30b was significantly down-regulated in gastric cancer cells and human gastric cancer tissues. Enforced expression of miR-30b promoted the apoptosis of gastric cancer cells in vitro, and miR-30b could significantly inhibit tumorigenicity of gastric cancer by increasing the apoptosis proportion of cancer cells in vivo. Moreover, plasminogen activator inhibitor-1 (PAI-1) was identified as the potential target of miR-30b, and miR-30b level was inversely correlated with PAI-1 expression in gastric cancer. In addition, silencing of PAI-1 was able to phenocopy the effect of miR-30b overexpression on apoptosis regulation of cancer cells, and overexpression of PAI-1 could suppressed the effect of promoting cell apoptosis by miR-30b, indicating PAI-1 is potentially involved in miR-30b-induced apoptosis on cancer cells. Conclusion miR-30b may function as a novel tumor suppressor gene in gastric cancer by targeting PAI-1 and regulating the apoptosis of cancer cells. miR-30b could serve as a potential biomarker and therapeutic target against gastric cancer. PMID:25170877

Zhu, En-Dong; Li, Na; Li, Bo-Sheng; Li, Wei; Zhang, Wei-Jun; Mao, Xu-Hu; Guo, Gang; Zou, Quan-Ming; Xiao, Bin

2014-01-01

314

Molecular mechanisms of liver injury: apoptosis or necrosis.  

PubMed

Hepatic apoptosis is thought of as a prevalent mechanism in most forms of liver injury. However, the role of hepatic apoptosis is often intermixed with the cellular necrosis. It remains unknown how apoptosis is relevant to the progression of the liver injury. This review summarizes the characteristics of both hepatic apoptosis and necrosis in pathogenesis of liver diseases. Apoptosis and necrosis represent alternative outcomes of different etiology during liver injury. Apoptosis is a main mode of cell death in chronic viral hepatitis, but is intermingled with necrosis in cholestatic livers. Necrosis is the principal type of liver cell killing in acetaminophen-induced hepatotoxicity. Anti-apoptosis as a strategy is beneficial to liver repair response. Therapeutic options of liver disease depend on the understanding toward pathogenic mechanisms of different etiology. PMID:24867271

Wang, Kewei

2014-10-01

315

Alternative calibration techniques for counteracting the matrix effects in GC-MS-SPE pesticide residue analysis - a statistical approach.  

PubMed

This paper investigates the efficiency of application of four different multivariate calibration techniques, namely matrix-matched internal standard (MMIS), matrix-matched external standard (MMES), solvent-only internal standard (SOIS) and solvent-only external standard (SOES) on the detection and quantification of 20 organochlorine compounds from high, low and blank matrix water sample matrices by Gas Chromatography-Mass Spectrometry (GC-MS) coupled to solid phase extraction (SPE). Further statistical testing, using Statistical Package for the Social Science (SPSS) by applying MANOVA, T-tests and Levene's F tests indicates that matrix composition has a more significant effect on the efficiency of the analytical method than the calibration method of choice. Matrix effects are widely described as one of the major sources of errors in GC-MS multiresidue analysis. Descriptive and inferential statistics proved that the matrix-matched internal standard calibration was the best approach to use for samples of varying matrix composition as it produced the most precise average mean recovery of 87% across all matrices tested. The use of an internal standard calibration overall produced more precise total recoveries than external standard calibration, with mean values of 77% and 64% respectively. The internal standard calibration technique produced a particularly high overall standard deviation of 38% at 95% confidence level indicating that it is less robust than the external standard calibration method which had an overall standard error of 32% at 95% confidence level. Overall, the matrix-matched external standard calibration proved to be the best calibration approach for analysis of low matrix samples which consisted of the real sample matrix as it had the most precise recovery of 98% compared to other calibration approaches for the low-matrix samples. PMID:24968235

Rimayi, Cornelius; Odusanya, David; Mtunzi, Fanyana; Tsoka, Shepherd

2015-01-01

316

Sustained adenosine exposure causes lung endothelial apoptosis: a possible contributor to cigarette smoke-induced endothelial apoptosis and lung injury.  

PubMed

Pulmonary endothelial cell (EC) apoptosis has been implicated in the pathogenesis of emphysema. Cigarette smoke (CS) causes lung EC apoptosis and emphysema. In this study, we show that CS exposure increased lung tissue adenosine levels in mice, an effect associated with increased lung EC apoptosis and the development of emphysema. Adenosine has a protective effect against apoptosis via adenosine receptor-mediated signaling. However, sustained elevated adenosine increases alveolar cell apoptosis in adenosine deaminase-deficient mice. We established an in vitro model of sustained adenosine exposure by incubating lung EC with adenosine in the presence of an adenosine deaminase inhibitor, deoxycoformicin. We demonstrated that sustained adenosine exposure caused lung EC apoptosis via nucleoside transporter-facilitated intracellular adenosine uptake, subsequent activation of p38 and JNK in mitochondria, and ultimately mitochondrial defects and activation of the mitochondria-mediated intrinsic pathway of apoptosis. Our results suggest that sustained elevated adenosine may contribute to CS-induced lung EC apoptosis and emphysema. Our data also reconcile the paradoxical effects of adenosine on apoptosis, demonstrating that prolonged exposure causes apoptosis via nucleoside transporter-mediated intracellular adenosine signaling, whereas acute exposure protects against apoptosis via activation of adenosine receptors. Inhibition of adenosine uptake may become a new therapeutic target in treatment of CS-induced lung diseases. PMID:23316066

Lu, Qing; Sakhatskyy, Pavlo; Newton, Julie; Shamirian, Paul; Hsiao, Vivian; Curren, Sean; Gabino Miranda, Gustavo Andres; Pedroza, Mesias; Blackburn, Michael R; Rounds, Sharon

2013-03-01

317

RSF1 Is a Positive Regulator of NF-?B–Induced Gene Expression Required for Ovarian Cancer Chemoresistance  

PubMed Central

Overexpression or amplification of the RSF1 gene has been associated with poor prognosis in various human cancers, including ovarian cancer. In previous work, RSF1 was identified as an amplified gene that facilitated the development of paclitaxel-resistant ovarian cancer. In the present study, we further demonstrated that RSF1 expression inversely correlated with paclitaxel response in patients with ovarian cancer and the mouse xenograft model. In addition, RSF1-overexpressing paclitaxel-resistant ovarian cancer cell lines were found to express elevated levels of genes regulated by NF-?B, including some involved with the evasion of apoptosis (CFLAR, XIAP, BCL2, and BCL2L1) and inflammation (PTGS2). In addition, ectopic expression of RSF1 using Tet-off inducible SKOV3 cells significantly enhanced NF-?B–dependent gene expression and transcriptional activation of NF-?B. An RSF1 knockdown using short hairpin RNAs suppressed these same pathways. Moreover, pretreatment with NF-?B inhibitors or downregulation of NF-?B–regulated gene expression considerably enhanced paclitaxel sensitivity in RSF1-overexpressing OVCAR3 and/or RSF1-induced SKOV3 cells. A coimmunoprecipitation assay revealed that RSF1 interacts with NF-?B and CREB-binding protein, a ubiquitous coactivator for NF-?B. Recruitment of RSF1 to the NF-?B binding element in the PTGS2 and XIAP promoters was demonstrated by the chromatin immunoprecipitation assay. Furthermore, hSNF2H, a well-known binding partner of RSF1, was partially involved in the interaction between RSF1 and NF-?B. Taken together, these data suggest that RSF1 may function as a coactivator for NF-?B, consequently augmenting expression of genes necessary for the development of chemoresistance in ovarian cancer cells. PMID:24566868

Yang, Yeong-In; Ahn, Ji-Hye; Lee, Kyung-Tae; Shin, Ie-Ming; Choi, Jung-Hye

2015-01-01

318

Targeting granulocyte apoptosis: mechanisms, models, and therapies.  

PubMed

The inflammatory process is a complex series of tightly controlled cellular and biochemical events initiated by the immune system, which has evolved to eliminate or contain infectious agents and to repair damaged tissue. Apoptosis is essential for the clearance of potentially injurious inflammatory cells, such as neutrophils, eosinophils, and basophils, and the subsequent efficient resolution of inflammation. In this review, we aim to cover key features of the granulocyte life-cycle ranging from their differentiation within the bone marrow to their maturation and ultimate clearance, with a focus on granulocyte apoptosis and macrophage efferocytosis. We further aim to discuss current and emerging models of inflammation and suggest novel ways of terminating or resolving deleterious inflammatory responses with a specific view to the translation of these strategies into fully realized, pro-resolution therapies. PMID:20636806

Duffin, Rodger; Leitch, Andrew E; Fox, Sarah; Haslett, Chris; Rossi, Adriano G

2010-07-01

319

Apoptosis, Stem Cells, and Tissue Regeneration  

NSDL National Science Digital Library

Tissue regeneration after wounding or amputation generally requires cell proliferation. Work in several model organisms, including Drosophila, Hydra, Xenopus, and mouse, revealed a surprising function for caspases in cell proliferation after tissue damage, in addition to their known role in a form of cell death called apoptosis. In apoptotic cells, caspases can stimulate the production of secreted cytokines, such as Wnt, bone morphogenetic protein (BMP), transforming growth factor–? (TGF-?), Hedgehog family members, and prostaglandins, which in turn induce proliferation of neighboring cells, thus promoting tissue regeneration and homeostasis. These pathways can also contribute to tumorigenesis. This Review summarizes findings on this phenomenon, termed “apoptosis-induced compensatory proliferation,” and contains three figures and 110 references.

Andreas Bergmann (MD Anderson Cancer Center; Department of Biochemistry and Molecular Biology REV)

2010-10-26

320

An update to DNA ladder assay for apoptosis detection  

PubMed Central

Introduction: A growing interest in apoptosis, programmed cell death, in the last years is observed and leads to better understanding of molecular mechanisms during cell–cell signaling, cell-environment interaction and screening of drugs. This in turn results in emerging of new assays and development of more accurate kits for fast and early detection of apoptosis. However, their sensitivity and reliability have often been scrutinized. Here we introduce a rapid and improved method of DNA ladder apoptosis assay for evaluating apoptosis in mammalian cells. Methods: NIH-3T3 cell line was used in this study. After treatment of cells with apoptotic agent, 500 ?M H2O2 at 48 hours, DNA was extracted. Then an update protocol of DNA ladder assay was applied for detection of apoptosis. Flow cytometry and DAPI staining were performed to verify apoptosis. Results: Primary and late apoptosis in the H2O2-treated cells was determined by flow cytometry analysis. DAPI Staining used to show DNA damage and DNA ladder assay using 1.5% gel electrophoresis showed fragmentation in the DNA of treated cells. Conclusion: In this research we aimed to improve DNA ladder assay to the high quality detection of apoptosis in mammalian cells. In our strategy, employing a practical DNA extraction protocol, DNA ladder assay could be applied as an easy/fast method for apoptosis detection. This improved method is able to detect apoptosis in a cost effective/timely manner without need for commercial kits and special equipment.

Rahbar Saadat, Yalda; Saeidi, Nazli; Zununi Vahed, Sepideh; Barzegari, Abolfazl; Barar, Jaleh

2015-01-01

321

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma.  

PubMed

Apoptosis-associated tyrosine kinase 1 (AATK1) was initially identified as a protein that was dramatically overexpressed during growth arrest and apoptosis of 32Dcl myeloblastic leukemia cells. AATK is expressed in different regions of the brain and may have a role in normal nervous system development by its dual functions of enhancing apoptosis of mature granule cells and promoting terminal neuronal differentiation of developing neurons. However, its function in cancer has never been studied. Melanoma is a tumor composed of transformed cells within the melanocyte lineage deriving from the embryonic neural crest. It has been shown that developmental pathways in neural crest cells have a direct bearing on melanoma formation and human metastatic melanoma cells express a dedifferentiated phenotype. We found that the expression levels of AATK are lower in metastatic melanoma cell lines compared with primary melanoma cell lines and normal human melanocytes. We found that depletion of AATK mRNA in metastatic melanoma cell lines enhanced cell migration in cell line derived from metastatic melanomas. Overexpression of AATK inhibited cell proliferation, colony formation, and promoted apoptosis in melanoma cell lines derived from primary and metastatic melanomas. Signal transduction pathway analysis revealed that Src is involved in regulating AATK. Our results demonstrate for the first time that AATK inhibits cell proliferation, colony formation, and migration, and also promotes apoptosis in melanoma cells. PMID:24589855

Ma, Shuang; Rubin, Brian P

2014-04-01

322

Apoptosis in amphibian organs during metamorphosis  

Microsoft Academic Search

During amphibian metamorphosis, the larval tissues\\/organs rapidly degenerate to adapt from the aquatic to the terrestrial\\u000a life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs\\u000a to ensure timely removal of larval organs\\/tissues and the development of adult ones for the survival of the individuals. Thus,\\u000a amphibian metamorphosis provides us a good

Atsuko Ishizuya-Oka; Takashi Hasebe; Yun-Bo Shi

2010-01-01

323

Noninvasive imaging of apoptosis in cardiovascular disease  

Microsoft Academic Search

Recent advances in molecular imaging have permitted the noninvasive imaging of apoptosis, a critical process underlying the\\u000a pathogenesis of many diseases of the cardiovascular system including atherosclerotic vascular disease, myocardial ischemia\\u000a and reperfusion injury, chronic heart failure, myocarditis, and cardiac allograft rejection. Multiple molecular targets including\\u000a phosphatidylserine, phosphatidylinositol 3-kinase, and caspases have been targeted by a variety of imaging agents

Ethan Chauncey Korngold; Farouc Amin Jaffer; Ralph Weissleder; David Edwin Sosnovik

2008-01-01

324

HIV-1 protease-induced apoptosis  

PubMed Central

Background Apoptosis is one of the presumptive causes of CD4+ T cell depletion during HIV infection and progression to AIDS. However, the precise role of HIV-1 in this process remains unexplained. HIV-1 protease (PR) has been suggested as a possible factor, but a direct link between HIV-1 PR enzymatic activity and apoptosis has not been established. Results Here, we show that expression of active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial apoptotic pathway. This conclusion is based on in vivo observations of the direct localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis. Moreover, we observed an HIV-1 PR concentration-dependent decrease in mitochondrial membrane potential and the role of HIV-1 PR in activation of caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22, VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two-hybrid screening, we also identified a new HIV-1 PR interaction partner, breast carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53 transcriptional activity on the bax promoter, thus elevating the cellular level of pro-apoptotic Bax protein. Conclusion In summary, our results describe the involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect of HIV-1 PR on mitochondrial membrane integrity or by its interaction with cellular protein BCA3. PMID:24886575

2014-01-01

325

Autophagy and apoptosis dysfunction in neurodegenerative disorders.  

PubMed

Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders. PMID:24211851

Ghavami, Saeid; Shojaei, Shahla; Yeganeh, Behzad; Ande, Sudharsana R; Jangamreddy, Jaganmohan R; Mehrpour, Maryam; Christoffersson, Jonas; Chaabane, Wiem; Moghadam, Adel Rezaei; Kashani, Hessam H; Hashemi, Mohammad; Owji, Ali A; ?os, Marek J

2014-01-01

326

BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS  

Microsoft Academic Search

? Abstract Caspase activation plays a central role in the execution of apoptosis. The key components,of the biochemical,pathways,of caspase activation have been recently elucidated. In this review, we focus on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway,and the mitochondria- initiated pathway. In the cell surface death receptor pathway, activation of caspase-8 following its

Imawati Budihardjo; Holt Oliver; Michael Lutter; Xu Luo; Xiaodong Wang

1999-01-01

327

Apoptosis and its functional significance in molluscs  

Microsoft Academic Search

Programmed cell death leading to apoptosis is essential for normal development and homeostasis in plants and throughout the\\u000a animal kingdom. Although there are differences in apoptotic mechanisms between lower animals and vertebrates, crucial biochemical\\u000a components of the programmed cell death pathways remained remarkably conserved throughout evolution. Despite decades of studies\\u000a on the neurobiology and development of mollusks, comparatively little is

Tibor Kiss

2010-01-01

328

Ionizing radiation sensitizes bone cells to apoptosis  

Microsoft Academic Search

Osteoradionecrosis is a common sequelae of radiation therapy for head and neck cancer. To test the hypothesis that radiation induces osteoradionecrosis by induction of bone cell apoptosis, we exposed MC3T3-E1 osteoblast-like cells to ?-radiation and evaluated cell viability. Twenty-four hours postirradiation, measurement of osteoblast dehydrogenase activity suggested that there was a small decrease in cell viability. However, TUNEL and flow

K. H Szymczyk; I. M Shapiro; C. S Adams

2004-01-01

329

Control of apoptosis by asymmetric cell division.  

PubMed

Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well. PMID:18399720

Hatzold, Julia; Conradt, Barbara

2008-04-01

330

Resistance of Actin to Cleavage during Apoptosis  

NASA Astrophysics Data System (ADS)

A small number of cellular proteins present in the nucleus, cytosol, and membrane fraction are specifically cleaved by the interleukin-1? -converting enzyme (ICE)-like family of proteases during apoptosis. Previous results have demonstrated that one of these, the cytoskeletal protein actin, is degraded in rat PC12 pheochromocytoma cells upon serum withdrawal. Extracts from etoposide-treated U937 cells are also capable of cleaving actin. It was assumed that cleavage of actin represented a general phenomenon, and a mechanism coordinating proteolytic, endonucleolytic, and morphological aspects of apoptosis was proposed. We demonstrate here that actin is resistant to degradation in several different human cells induced to undergo apoptosis in response to a variety of stimuli, including Fas ligation, serum withdrawal, cytotoxic T-cell killing, and DNA damage. On the other hand, cell-free extracts from these cells and the ICE-like protease CPP32 were capable of cleaving actin in vitro. We conclude that while actin contains cleavage sites for ICE-like proteases, it is not degraded in vivo in human cells either because of lack of access of these proteases to actin or due to the presence of other factors that prevent degradation.

Song, Qizhong; Wei, Tie; Lees-Miller, Susan; Alnemri, Emad; Watters, Dianne; Lavin, Martin F.

1997-01-01

331

Ion channels and apoptosis in cancer  

PubMed Central

Humans maintain a constant cell number throughout their lifespan. This equilibrium of cell number is accomplished when cell proliferation and cell death are kept balanced, achieving a steady-state cell number. Abnormalities in cell growth or cell death can lead to an overabundance of cells known as neoplasm or tumours. While the perception of cancer is often that of an uncontrollable rate of cell growth or increased proliferation, a decrease in cell death can also lead to tumour formation. Most cells when detached from their normal tissue die. However, cancer cells evade cell death, tipping the balance to an overabundance of cell number. Therefore, overcoming this resistance to cell death is a decisive factor in the treatment of cancer. Ion channels play a critical role in cancer in regards to cell proliferation, malignant angiogenesis, migration and metastasis. Additionally, ion channels are also known to be critical components of apoptosis. In this review, we discuss the modes of cell death focusing on the ability of cancer cells to evade apoptosis. Specifically, we focus on the role ion channels play in controlling and regulating life/death decisions and how they can be used to overcome resistance to apoptosis in the treatment of cancer. PMID:24493752

Bortner, Carl D.; Cidlowski, John A.

2014-01-01

332

Lithium protects ethanol-induced neuronal apoptosis  

SciTech Connect

Lithium is widely used for the treatment of bipolar disorder. Recent studies have demonstrated its neuroprotective effect. Ethanol is a potent neurotoxin that is particularly harmful to the developing nervous system. In this study, we evaluated lithium's neuroprotection against ethanol-induced apoptosis. Transient exposure of infant mice to ethanol caused apoptotic cell death in brain, which was prevented significantly by administering a low dose of lithium 15 min later. In cultured cerebellar granule neurons, ethanol-induced apoptosis and activation of caspase-3/9, both of which were prevented by lithium. However, lithium's protection is not mediated by its commonly known inhibition of glycogen synthase3{beta}, because neither ethanol nor lithium has significant effects on the phosphorylation of Akt (ser473) or GSK3{beta} (ser9). In addition, the selective GSK-3{beta} inhibitor SB-415286 was unable to prevent ethanol-induced apoptosis. These data suggest lithium may be used as a potential preventive measure for ethanol-induced neurological deficits.

Zhong Jin [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)]. E-mail: jizhong@iupui.edu; Yang Xianlin [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Yao Weiguo [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Lee Weihua [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)

2006-12-01

333

HIV increases HCV-induced hepatocyte apoptosis  

PubMed Central

Background and Aims HCV related liver disease is one of the most important complications in persons with HIV, with accelerated fibrosis progression in coinfected persons compared to those with HCV alone. We hypothesized that HIV coinfection increases HCV related hepatocyte apoptosis and that HCV and HIV influence TRAIL signaling in hepatocytes. Methods We analyzed the effect of HIV on JFH1-infected Huh 7.5.1 cells. Apoptosis was measured by Caspase-Glo 3/7 assay and Western blot for cleaved PARP. TRAIL, TRAIL receptor 1 (DR4) and 2 (DR5) mRNA and protein levels were assessed by real-time PCR and Western blot. We also investigated activation of caspase pathways using caspase inhibitors and assessed expression of Bid and cytochrome C. Results We found increased caspase 3/7 activity and cleaved PARP in JFH1 HCV-infected Huh7.5.1 cells in the presence of heat-inactivated HIV compared to Huh7.5.1 cells infected with JFH1 or exposed to heat-inactivated HIV alone. Both DR4 and DR5 mRNA and protein expression were increased in JFH1-infected cells in the presence of inactivated HIV compared to Huh7.5.1 cells infected with JFH1 or exposed to heat-inactivated HIV alone. Pancaspase, Caspase-8, and caspase-9 inhibition blocked apoptosis induced by HCV, inactivated HIV and HCV plus inactivated HIV. A caspase-9 inhibitor blocked apoptosis induced by HCV, HIV and HCV-HIV comparably to pancaspase and caspase-8 inhibitors. HCV induced the activation of Bid cleavage and cytochrome C release. The addition of HIV substantially augmented this induction. Conclusions Our findings indicate that hepatocyte apoptosis is increased in the presence of HCV and HIV compared to HCV or HIV alone, and that this increase is mediated by DR4 and DR5 up-regulation. They provide an additional mechanism for the observed accelerated liver disease progression observed in HCV-HIV coinfection. PMID:21146890

Jang, Jae Young; Shao, Run-Xuan; Lin, Wenyu; Weinberg, Ethan; Chung, Woo Jin; Tsai, Wei Lun; Zhao, Hong; Goto, Kaku; Zhang, Leiliang; Mendez-Navarro, Jorge; Jilg, Nikolaus; Peng, Lee F.; Brockman, Mark A.; Chung, Raymond T.

2010-01-01

334

Artesunate induces AIF-dependent apoptosis in A549 cells  

NASA Astrophysics Data System (ADS)

Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. It has been shown that ART induces cancer cells death through apoptosis pathway. This study investigated whether ART treatment induced reactive oxygen species (ROS)-dependent cell death in the apoptosis fashion in human lung adenocarconoma A549 cell line and the proapoptotic protein apoptosis inducing factor (AIF) is involved in ART-induced apoptosis. Cells treated with ART exhibited typical apoptotic morphology as chromatin condensation, margination and shrunken nucleus. ART treatment also induced a loss of mitochondrial membrane potential and AIF release from mitochondria. Silencing AIF can remarkable attenuated ART-induced apoptosis. Collectively, ART induces apoptosis by caspase-independent intrinsic pathway in A549 cells.

Zhou, Chen-juan; Chen, Tong-Sheng

2012-03-01

335

Apoptosis as a Mechanism for Liver Disease Progression  

PubMed Central

Hepatocyte injury is ubiquitous in clinical practice, and the mode of cell death associated with this injury is often apoptosis, especially by death receptors. Information from experimental systems demonstrates that hepatocyte apoptosis is sufficient to cause liver hepatic fibrogenesis. The mechanisms linking hepatocyte apoptosis to hepatic fibrosis remain incompletely understood, but likely relate to engulfment of apoptotic bodies by professional phagocytic cells and stellate cells, and release of mediators by cells undergoing apoptosis. Inhibition of apoptosis with caspase inhibitors has demonstrated beneficial effects in murine models of hepatic fibrosis. Recent studies implicating Toll-like receptor 9 (TLR9) in liver injury and fibrosis are also of particular interest. Engulfment of apoptotic bodies is one mechanism by which the TLR9 ligand (CpG DNA motifs) could be delivered to this intracellular receptor. These concepts suggest therapy focused on interrupting the cellular mechanisms linking apoptosis to fibrosis would be useful in human liver diseases. PMID:20960379

Guicciardi, Maria Eugenia; Gores, Gregory J.

2011-01-01

336

Paraquat Induces Apoptosis through Cytochrome C Release and ERK Activation  

PubMed Central

Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells. PMID:25489417

Seo, Hong Joo; Choi, Sang Joon; Lee, Jung-Hee

2014-01-01

337

Orally Administered Fructose Increases the Numbers of Peripheral Lymphocytes Reduced by Exposure of Mice to Gamma or SPE-like Proton Radiation.  

PubMed

Exposure of the whole body or a major portion of the body to ionizing radiation can result in Acute Radiation Sickness (ARS), which can cause symptoms that range from mild to severe, and include death. One of the syndromes that can occur during ARS is the hematopoietic syndrome, which is characterized by a reduction in bone marrow cells as well as the number of circulating blood cells. Doses capable of causing this syndrome can result from conventional radiation therapy and accidental exposure to ionizing radiation. It is of concern that this syndrome could also occur during space exploration class missions in which astronauts could be exposed to significant doses of solar particle event (SPE) radiation. Of particular concern is the reduction of lymphocytes and granulocytes, which are major components of the immune system. A significant reduction in their numbers can compromise the immune system, causing a higher risk for the development of infections which could jeopardize the success of the mission. Although there are no specific countermeasures utilized for the ARS resulting from exposure to space radiation(s), granulocyte colony-stimulating factor (G-CSF) has been proposed as a countermeasure for the low number of neutrophils caused by SPE radiation, but so far no countermeasure exists for a reduced number of circulating lymphocytes. The present study demonstrates that orally administered fructose significantly increases the number of peripheral lymphocytes reduced by exposure of mice to 2 Gy of gamma- or SPE-like proton radiation, making it a potential countermeasure for this biological end-point. PMID:25360417

Romero-Weaver, A L; Ni, J; Lin, L; Kennedy, A R

2014-07-01

338

Signs of apoptosis of immunocompetent cells in patients with depression  

Microsoft Academic Search

A total of 26 patients with depression and 20 healthy subjects were studied. Measures of apoptosis of peripheral blood lymphocytes\\u000a and serum cortisol concentrations were determined. A significant increase in lymphocyte apoptosis was found in patients with\\u000a depression, resulting in an increase in the proportion of lymphocytes expressing the FAS receptor; cells with morphological\\u000a signs characteristic of apoptosis (nuclear condensation,

S. A. Ivanova; V. Ya. Semke; T. P. Vetlugina; N. M. Rakitina; T. A. Kudyakova; G. G. Simutkin

2007-01-01

339

A Novel Protein Expressed in Mammalian Cells Undergoing Apoptosis  

Microsoft Academic Search

Human and rodent cells undergoing apoptosis were observed to express high levels of a novel 45,000 Mr protein. The protein, which we have termed apoptosis specific protein (ASP), was found in Burkitt lymphoma (BL) cells and in adenovirus-transformed human and rat embryo cells induced into apoptosis by a variety of stimuli, including serum deprivation, exposure to the Ca2+ ionophore, ionomycin,

Roger J. A. Grand; Anne E. Milner; Tracey Mustoe; Gerald D. Johnson; Darerca Owen; Michael L. Grant; Christopher D. Gregory

1995-01-01

340

Fate of the Nuclear Lamina during Caenorhabditis elegans Apoptosis  

Microsoft Academic Search

Invertebrates and in Drosophila, lamins and lamin-associated proteins are primary targets for cleavage by caspases. Eliminating mammalian lamins causes apoptosis, whereas expressing mutant lamins that cannot be cleaved by caspase-6 delay apoptosis. Caenorhabditis elegans has a single lamin protein, Ce-lamin, and a caspase, CED-3, that is responsible for most if not all somatic apoptosis. In this study we show that

Yonatan B. Tzur; Bradley M. Hersh; H. Robert Horvitz; Yosef Gruenbaum

2002-01-01

341

Rybp interacts with Hippi and enhances Hippi-mediated apoptosis  

Microsoft Academic Search

Rybp (DEDAF) has been shown to interact with DED-containing proteins and to encode pro-apoptotic functions. Here we characterize\\u000a a novel interaction between Rybp and Hippi, a protein implicated in neuronal apoptosis as well as in the pathogenesis of Huntington’s\\u000a disease. Rybp can synergize with Hippi to enhance Caspase 8-mediated apoptosis and also appears to be essential for Hippi-mediated\\u000a apoptosis. Moreover,

Sasha E. Stanton; Jennifer K. Blanck; Joseph Locker; Nicole Schreiber-Agus

2007-01-01

342

Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells  

PubMed Central

Homeostasis of the gastrointestinal epithelium is dependent upon a balance between cell proliferation and apoptosis. Cyclin-dependent kinases (Cdks) are well known for their role in cell proliferation. Previous studies from our group have shown that polyamine-depletion of intestinal epithelial cells (IEC-6) decreases cyclin-dependent kinase 2 (Cdk2) activity, increases p53 and p21Cip1 protein levels, induces G1 arrest, and protects cells from camptothecin (CPT)-induced apoptosis. Although emerging evidence suggests that members of the Cdk family are involved in the regulation of apoptosis, their roles directing apoptosis of IEC-6 cells are not known. In this study, we report that inhibition of Cdk1, 2, and 9 (with the broad range Cdk inhibitor, AZD5438) in proliferating IEC-6 cells triggered DNA damage, activated p53 signaling, inhibited proliferation, and induced apoptosis. By contrast, inhibition of Cdk2 (with NU6140) increased p53 protein and activity, inhibited proliferation, but had no effect on apoptosis. Notably, AZD5438 sensitized, whereas, NU6140 rescued proliferating IEC-6 cells from CPT-induced apoptosis. However, in colon carcinoma (Caco2) cells with mutant p53, treatment with either AZD5438 or NU6140 blocked proliferation, albeit more robustly with AZD5438. Both Cdk inhibitors induced apoptosis in Caco2 cells in a p53-independent manner. In serum starved quiescent IEC-6 cells, both AZD5438 and NU6140 decreased TNF- /CPT-induced activation of p53 and, consequently, rescued cells from apoptosis, indicating that sustained Cdk activity is required for apoptosis of quiescent cells. Furthermore, AZD5438 partially reversed the protective effect of polyamine depletion whereas NU6140 had no effect. Together, these results demonstrate that Cdks possess opposing roles in the control of apoptosis in quiescent and proliferating cells. In addition, Cdk inhibitors uncouple proliferation from apoptosis in a p53-dependent manner. PMID:24242917

Bhattacharya, Sujoy; Ray, Ramesh M.; Johnson, Leonard R.

2014-01-01

343

Implication of Polyamines in Apoptosis of Immunoresponse Cells  

Microsoft Academic Search

In many diseases, including host response to pathogens, dysregulation of the immune system is a hallmark. An important component\\u000a of such events is alterations in apoptosis of immune cells. This may include failure of apoptosis, but most commonly involves\\u000a loss of immune function from death of immune cells. We will review the role of polyamines in immune cell apoptosis and

Rupesh Chaturvedi; Keith T. Wilson

344

Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells.  

PubMed

Homeostasis of the gastrointestinal epithelium is dependent upon a balance between cell proliferation and apoptosis. Cyclin-dependent kinases (Cdks) are well known for their role in cell proliferation. Previous studies from our group have shown that polyamine-depletion of intestinal epithelial cells (IEC-6) decreases cyclin-dependent kinase 2 (Cdk2) activity, increases p53 and p21Cip1 protein levels, induces G1 arrest, and protects cells from camptothecin (CPT)-induced apoptosis. Although emerging evidence suggests that members of the Cdk family are involved in the regulation of apoptosis, their roles directing apoptosis of IEC-6 cells are not known. In this study, we report that inhibition of Cdk1, 2, and 9 (with the broad range Cdk inhibitor, AZD5438) in proliferating IEC-6 cells triggered DNA damage, activated p53 signaling, inhibited proliferation, and induced apoptosis. By contrast, inhibition of Cdk2 (with NU6140) increased p53 protein and activity, inhibited proliferation, but had no effect on apoptosis. Notably, AZD5438 sensitized, whereas, NU6140 rescued proliferating IEC-6 cells from CPT-induced apoptosis. However, in colon carcinoma (Caco-2) cells with mutant p53, treatment with either AZD5438 or NU6140 blocked proliferation, albeit more robustly with AZD5438. Both Cdk inhibitors induced apoptosis in Caco-2 cells in a p53-independent manner. In serum starved quiescent IEC-6 cells, both AZD5438 and NU6140 decreased TNF-?/CPT-induced activation of p53 and, consequently, rescued cells from apoptosis, indicating that sustained Cdk activity is required for apoptosis of quiescent cells. Furthermore, AZD5438 partially reversed the protective effect of polyamine depletion whereas NU6140 had no effect. Together, these results demonstrate that Cdks possess opposing roles in the control of apoptosis in quiescent and proliferating cells. In addition, Cdk inhibitors uncouple proliferation from apoptosis in a p53-dependent manner. PMID:24242917

Bhattacharya, Sujoy; Ray, Ramesh M; Johnson, Leonard R

2014-03-01

345

Fully automated trace level determination of parent and alkylated PAHs in environmental waters by online SPE-LC-APPI-MS/MS.  

PubMed

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous compounds that enter the environment from natural and anthropogenic sources, often used as markers to determine the extent, fate, and potential effects on natural resources after a crude oil accidental release. Gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction (LLE+GC-MS) has been extensively used to isolate and quantify both parent and alkylated PAHs. However, it requires labor-intensive extraction and cleanup steps and generates large amounts of toxic solvent waste. Therefore, there is a clear need for greener, faster techniques with enough reproducibility and sensitivity to quantify many PAHs in large numbers of water samples in a short period of time. This study combines online solid-phase extraction followed by liquid chromatography (LC) separation with dopant-assisted atmospheric pressure photoionization (APPI) and tandem MS detection, to provide a one-step protocol that detects PAHs at low nanograms per liter with almost no sample preparation and with a significantly lower consumption of toxic halogenated solvents. Water samples were amended with methanol, fortified with isotopically labeled PAHs, and loaded onto an online SPE column, using a large-volume sample loop with an auxiliary LC pump for sample preconcentration and salt removal. The loaded SPE column was connected to an UPLC pump and analytes were backflushed to a Thermo Hypersil Green PAH analytical column where a 20-min gradient separation was performed at a variable flow rate. Detection was performed by a triple-quadrupole MS equipped with a gas-phase dopant delivery system, using 1.50 mL of chlorobenzene dopant per run. In contrast, LLE+GC-MS typically use 150 mL of organic solvents per sample, and methylene chloride is preferred because of its low boiling point. However, this solvent has a higher environmental persistence than chlorobenzene and is considered a carcinogen. The automated system is capable of performing injection, online SPE, inorganic species removal, LC separation, and MS/MS detection in 28 min. Selective reaction monitoring was used to detect 28 parent PAHs and 15 families of alkylated PAHs. The methodology is comparable to traditional GC-MS and was tested with surface seawater, rainwater runoff, and a wastewater treatment plant effluent. Positive detections above reporting limits are described. The virtual absence of sample preparation could be particularly advantageous for real-time monitoring of discharge events that introduce PAHs into environmental compartments, such as accidental releases of petroleum derivates and other human-related events. This work covers optimization of APPI detection and SPE extraction efficiency, a comparison with LLE+GC-MS in terms of sensitivity and chromatographic resolution, and examples of environmental applications. PMID:24217946

Ramirez, Cesar E; Wang, Chengtao; Gardinali, Piero R

2014-01-01

346

Quantitative analysis of six polyynes and one polyene in Oplopanax horridus and Oplopanax elatus by pressurized liquid extraction and on-line SPE–HPLC  

Microsoft Academic Search

A pressurized liquid extraction and on-line SPE–HPLC method was developed for simultaneous determination of six polyynes, including falcarindiol, oplopandiol, (11S,16S,9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate, oplopandiol acetate, oplopantriol A, oplopantriol B, and one polyene, (S,E)-nerolidol, in Oplopanax horridus and Oplpanax elatus. The analysis was conducted on a Grace Prevail C18 column (3?m, 7mm×33mm) with gradient elution of acetonitrile and water after the sample loaded and

Weihua Huang; Jing Yang; Jing Zhao; Chong-zhi Wang; Chun-su Yuan; Shao-ping Li

2010-01-01

347

Apoptosis in vascular cells induced by cold atmospheric plasma treatment  

NASA Astrophysics Data System (ADS)

Apoptosis is a natural mechanism of cellular self-destruction. It can be triggered by moderate, yet irreversible damage. Apoptosis plays a major role in tissue renewal. Artificial apoptosis induction will become a novel therapy that meets all requirements for tissue-saving surgery. Diseased tissues can disappear without inflammation and scarring. This is particularly important in treatment of blockages in body tracts (e.g. cardiovascular diseases). Artificial induction of apoptosis can be achieved by means of cold plasma treatment. In this work an atmospheric micro-plasma operated in helium/air has been used to induce apoptosis in vascular cells. Parametric studies of apoptosis induction have been conducted; the efficiency is almost 100%. The apoptotic factors are ROS/RNS (reactive oxygen and nitrogen species). Their densities in the plasma have been measured by mass spectrometry. For apoptosis induction, RNS seem to be more important than ROS, because of their relative abundance. Moreover, addition of a ROS scavenger (ascorbic acid) to the cell culture medium does not reduce the occurrence of apoptosis. Cold plasma is a very efficient tool for fundamental studies of apoptosis, and later, for controlled tissue removal in vivo.

Sladek, Raymond; Stoffels, Eva

2006-10-01

348

Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.  

PubMed

The present studies investigated the effects of tacrine, a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H(2)O(2))-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H(2)O(2) (100 microM) triggered typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed upregulated p53 and bax mRNA levels with H(2)O(2) treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with tacrine significantly attenuated H(2)O(2)-induced injury, prevented the cells from apoptosis and attenuated H(2)O(2)-induced overexpression of bax and p53. The present findings suggest that tacrine exert significant protection against H(2)O(2)-induced apoptosis possibly through inhibiting expression of pro-apoptosis genes. PMID:12414117

Wang, Rui; Zhou, Jin; Tang, Xi Can

2002-10-30

349

CHEMOSENSITIZATION BY A NON-APOPTOGENIC HEAT SHOCK PROTEIN 70-BINDING APOPTOSIS INDUCING FACTOR MUTANT  

EPA Science Inventory

Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis inducing factor mutant Abstract HSP70 inhibits apoptosis by neutralizing the caspase activator Apaf-1 and by interacting with apoptosis inducing factor (AIF), a mitochondrial flavoprotein wh...

350

Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic T-Lymphocyte-Induced Apoptosis  

Microsoft Academic Search

Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the \\

KEITH R. JEROME; JONATHAN F. TAIT; DAVID M. KOELLE; LAWRENCE COREY

1998-01-01

351

Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor of apoptosis  

E-print Network

Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor protein Grim abrogated human caspase suppression by SfIAP and CpIAP, imply- ing evolutionary conservation for their antiapoptotic function in insect cells. Cellular IAP homologs are found in many animal species, including

Hammock, Bruce D.

352

Measuring and Modeling Apoptosis in Single Cells  

PubMed Central

Cell death plays an essential role in the development of tissues and organisms, the etiology of disease, and the responses of cells to therapeutic drugs. Here we review progress made over the last decade in using mathematical models and quantitative, often single-cell, data to study apoptosis. We discuss the delay that follows exposure of cells to prodeath stimuli, control of mitochondrial outer membrane permeabilization, switch-like activation of effector caspases, and variability in the timing and probability of death from one cell to the next. Finally, we discuss challenges facing the fields of biochemical modeling and systems pharmacology. PMID:21414484

Spencer, Sabrina L.; Sorger, Peter K.

2011-01-01

353

Tumor Necrosis Factor ?-induced Inflammation Is Increased but Apoptosis Is Inhibited by Common Food Additive Carrageenan*  

PubMed Central

Tumor necrosis factor (TNF)-?, a homotrimeric, pleiotropic cytokine, is secreted in response to inflammatory stimuli in diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-? mediates both apoptosis and inflammation, stimulating an inflammatory cascade through the non-canonical pathway of NF-?B activation, leading to increased nuclear RelB and p52. In contrast, the common food additive carrageenan (CGN) stimulates inflammation through both the canonical and non-canonical pathways of NF-?B activation and utilizes the adaptor molecule BCL10 (B-cell leukemia/lymphoma 10). In a series of experiments, colonic epithelial cells and mouse embryonic fibroblasts were treated with TNF-? and carrageenan in order to simulate the possible effects of exposure to dietary CGN in the setting of a TNF-?-mediated inflammatory disease process. A marked increase in secretion of IL-8 occurred, attributable to synergistic effects on phosphorylated NF-?B-inducing kinase (NIK) in the non-canonical pathway. TNF-? induced the ubiquitination of TRAF2 (TNF receptor-associated factor 2), which interacts with NIK, and CGN induced phosphorylation of BCL10, leading to increased NIK phosphorylation. These results suggest that TNF-? and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of the non-canonical pathway of NF-?B activation. In contrast, the apoptotic effects of TNF-?, including activation of caspase-8 and PARP-1 (poly(ADP-ribose) polymerase 1) fragmentation, were markedly reduced in the presence of CGN, and CGN caused reduced expression of Fas. These findings demonstrate that exposure to CGN drives TNF-?-stimulated cells toward inflammation rather than toward apoptotic cell death and suggest that CGN exposure may compromise the effectiveness of anti-TNF-? therapy. PMID:20937806

Bhattacharyya, Sumit; Dudeja, Pradeep K.; Tobacman, Joanne K.

2010-01-01

354

SPE coupled with dispersive liquid-liquid microextraction followed by GC with flame ionization detection for the determination of ultra-trace amounts of benzodiazepines.  

PubMed

SPE combined with dispersive liquid-liquid microextration was used for the extraction of ultra-trace amounts of benzodiazepines (BZPs) including, diazepam, midazolam, and alprazolam, from ultra-pure water, tap water, fruit juices, and urine samples. The analytes were adsorbed from large volume samples (60 mL) onto octadecyl silica SPE columns. After the elution of the desired compounds from sorbents with 2.0 mL acetone, 0.5 mL of eluent containing 40.0 ?L chloroform was injected rapidly into 4.5 mL pure water. After extraction and centrifugation, 2 ?L of the sedimented phase was injected into a GC equipped with a flame ionization detector. Several parameters affecting this process were investigated and optimized. Under the optimal conditions, LODs ranged from 0.02 to 0.05 ?g/L, a linear dynamic range of 0.1-100 ?g/L and relative SDs in the range of 4.4-10.7% were attained. Very high preconcentration factors ranging from 3895-7222 were achieved. The applicability of the method for the extraction of BZPs from different types of complicated matrices, such as tap water, fruit juices, and urine samples, was studied. The obtained results reveal that the proposed method is a good technique for the extraction and determination of BZPs in complex matrices. PMID:24243833

Ghobadi, Masoomeh; Yamini, Yadollah; Ebrahimpour, Behnam

2014-02-01

355

The SpeX Prism Library: 1000+ low-resolution, near-infrared spectra of ultracool M, L, T and Y dwarfs  

NASA Astrophysics Data System (ADS)

The SpeX Prism Library (SPL) is a uniform compilation of low-resolution (?/?? ? 75-120), near-infrared (0.8--2.5 ?m) spectra spanning a decade of observations with the IRTF SpeX spectrograph. Primarily containing ultracool M, L, T and Y dwarfs, this spectral library has been used in over 100 publications to date, facilitating a broad range of science on low mass stars, exoplanets, high redshift sources and instrument/survey design. I summarize the contents of the SPL and highlight a few of the key scientific results that have made use of this resource, as well as applications in education, outreach and art. I also outline the future plans of the SPL, which include a reanalysis of early data, better integration and dissemination of source and spectral metadata, conversion to Virtual Observatory formats, development of a Python software package for community analysis, and a design for a node-based visual programming platform that can facilitate citizen science and project-based learning in stellar spectroscopy. http://www.browndwarfs.org/spexprism

Burgasser, Adam J.

356

Simultaneous determination of isoflavones and resveratrols for adulteration detection of soybean and peanut oils by mixed-mode SPE LC-MS/MS.  

PubMed

To ensure authenticity of vegetable oils, isoflavones (genistein, genistin, daidzein and daidzin) and resveratrols (cis-resveratrol and trans-resveratrol) were selected as the putative markers for adulteration of soybean and peanut oils. Firstly, mixed mode solid-phase extraction coupled with liquid chromatography tandem mass spectrometry (mixed-mode SPE LC-MS/MS) method was developed to analyze isoflavones and resveratrols in vegetable oils. The concentration of marker compounds in vegetable oils were 0.08-1.47mgkg(-1) for daidzein, ND-78.9?gkg(-1) for daidzin, 0.40-5.89mgkg(-1) for genistein, 1.2-114.9?gkg(-1) for genistin, 3.1-85.0?gkg(-1) for trans-resveratrol and 1.9-51.0?gkg(-1) for cis-resveratrol, which are compatible with the raw materials for oil press. Additionally, the applicability of this method has been successfully tested in thirteen vegetable oils from the market. Mixed-mode SPE LC-MS/MS method can simultaneously detect isoflavones and resveratrols in vegetable oils and assess adulteration and quality of soybean and peanut oils. PMID:25624257

Zhao, Xin; Ma, Fei; Li, Peiwu; Li, Guangming; Zhang, Liangxiao; Zhang, Qi; Zhang, Wen; Wang, Xiupin

2015-06-01

357

Semi-preparative LC-SPE-cryoflow NMR for impurity identifications: use of mother liquor as a better source of impurities.  

PubMed

Unambiguous structural elucidation of active pharmaceutical ingredients (API) impurities is a particularly challenging necessity of pharmaceutical development, particularly if the impurities are low level (0.1% level). In many cases, this requires acquiring high-quality NMR data on a pure sample of each impurity. High-quality, high signal-to-noise (S/N) one- and two-dimensional NMR data can be obtained using liquid chromatography-solid phase extraction-cryoflow NMR (LC-SPE-cryoflow NMR) with a combination of semi-preparative column for separation and mother liquor as a source of concentrated impurities. These NMR data, in conjunction with mass spectrometry data, allowed for quick and unambiguous structural elucidations of four impurities found at low level in the crystallized API but found at appreciable levels in the mother liquor that was used as the source for these impurities. These data show that semi-preparative columns can be used at lower than ideal flow rates to facilitate trapping of HPLC components for LC-SPE-cryoflow NMR analysis without compromising chromatographic resolution. Also, despite the complex chromatography encountered with the use of mother liquor as a source of impurities, acceptably pure analytes were obtained for acquiring NMR data for unambiguous structure elucidations. PMID:23788325

Rinaldi, Frank; Fan, Junying; Pathirana, Charles; Palaniswamy, Venkatapurim

2013-09-01

358

Measurement of bisphenol A, bisphenol A ß-d-glucuronide, genistein, and genistein 4?-ß-d-glucuronide via SPE and HPLC-MS/MS  

PubMed Central

Bisphenol A (BPA) is a synthetic industrial reactant used in the production of polycarbonate plastics, and genistein is a natural phytoestrogen abundant in the soybean. Current studies investigating the endocrinedisrupting effects of concomitant exposures to BPA and genistein have warranted the development of an analytical method for the simultaneous measurement of BPA and genistein, as well as their primary metabolites, bisphenol A ß-d-glucuronide (BPA gluc) and genistein 4?-ß-d-glucuronide (genistein gluc), respectively. All four analytes were extracted from rat plasma via solid phase extraction (SPE). Three SPE cartridges and four elution schemes were tested. Plasma extraction using Bond Elut Plexa cartridges with sequential addition of ethyl acetate, methanol, and acetonitrile yielded optimal average recoveries of 98.1±1.8% BPA, 94.9±8.0% genistein, 91.4±6.1% BPA gluc, and 103±6.1% genistein gluc. Identification and quantification of the four analytes were performed by a validated HPLC-MS/MS method using electrospray ionization and selective reaction monitoring. This novel analytical method should be applicable to the measurement of BPA, genistein, BPA gluc, and genistein gluc in urine, cultures, and tissue following in vivo exposures. While reports of the determination of BPA and genistein independently exist, the simultaneous optimized extraction and detection of BPA, genistein, BPA gluc, and genistein gluc have not previously been reported. PMID:21667348

Coughlin, Janis L.; Winnik, Bozena

2015-01-01

359

The SpeX Prism Library: 1000+ Low-resolution, Near-infrared Spectra of Ultracool M, L, T and Y Dwarfs  

E-print Network

The SpeX Prism Library (SPL) is a uniform compilation of low-resolution (R ~ 75-120), near-infrared (0.8-2.5 micron) spectra spanning a decade of observations with the IRTF SpeX spectrograph. Primarily containing ultracool M, L, T and Y dwarfs, this spectral library has been used in over 100 publications to date, facilitating a broad range of science on low mass stars, exoplanets, high redshift sources and instrument/survey design. I summarize the contents of the SPL and highlight a few of the key scientific results that have made use of this resource, as well as applications in education, outreach and art. I also outline the future plans of the SPL, which include a reanalysis of early data, better integration and dissemination of source and spectral metadata, conversion to Virtual Observatory formats, development of a Python software package for community analysis, and a design for a node-based visual programming platform that can facilitate citizen science and project-based learning in stellar spectroscopy.

Burgasser, Adam J

2014-01-01

360

On-line SPE-UHPLC method using fused core columns for extraction and separation of nine illegal dyes in chilli-containing spices.  

PubMed

The presented work describes the development of a simple, fast and effective on-line SPE-UHPLC-UV/vis method using fused core particle columns for extraction, separation and quantitative analysis of the nine illegal dyes, most frequently found in chilli-containing spices. The red dyes Sudan I-IV, Sudan Red 7B, Sudan Red G, Sudan Orange G, Para Red, and Methyl Red were separated and analyzed in less than 9 min without labor-consuming pretreatment procedure. The chromatographic separation was performed on Ascentis Express RP-Amide column with gradient elution using mixture of acetonitrile and water, as a mobile phase at a flow rate of 1.0 mL min(-1) and 55°C of temperature. As SPE sorbent for cleanup and pre-concentration of illegal dyes short guard fused core column Ascentis Express F5 was used. The applicability of proposed method was proven for three different chilli-containing commercial samples. Recoveries for all compounds were between 90% and 108% and relative standard deviation ranged from 1% to 4% for within- and from 2% to 6% for between-day. Limits of detection showed lower values than required by European Union regulations and were in the range of 3.3-10.3 µg L(-1) for standard solutions, 5.6-235.6 µg kg(-1) for chilli-containing spices. PMID:25159432

Khalikova, Maria A; Satínský, Dalibor; Smidrkalová, Tereza; Solich, Petr

2014-12-01

361

Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria.  

PubMed

Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 pro?cient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status. PMID:25395275

Zhang, Xiali; Lu, Hongfei; Wang, Yibing; Liu, Chunju; Zhu, Weifeng; Zheng, Shuangyan; Wan, Fusheng

2015-01-01

362

Determination of pesticide residues in fish tissues by modified QuEChERS method and dual-d-SPE clean-up coupled to gas chromatography-mass spectrometry.  

PubMed

The aim of this research was to modify the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method for the determination of organochlorine and organophosphate pesticides in fatty animal matrices such as fish muscle tissues of carp and sturgeon collected from Carp Valley, Lesser Poland. Pesticides extraction effectiveness was evaluated at 0.030 mg kg(-1) spiking level and efficiency of the dispersive-solid-phase extraction (d-SPE) clean-up step was evaluated by comparison testing two different d-SPE clean-up stages, first the addition of the d-SPE sorbent combination (PSA?+?SAX?+?NH2), and secondly the addition of C18 after extracts enrichment with the d-SPE sorbent combination (PSA?+?SAX?+?NH2), introducing a novel concept of clean-up named dual-d-SPE clean-up. Analysis of pesticide residues was performed by Gas Chromatography Quadrupole Mass Spectrometry (GC/Q-MS) working in selected-ion monitoring (SIM) mode. Linear relation was observed from 0 to 200 ng mL(-1) and determination coefficient R(2)?>?0.997 in all instances for all target analytes. Better recoveries and cleanliness of extracts in both samples, carp and sturgeon tissues, were obtained after C18 addition during the dual-d-SPE clean-up step. Recoveries were in the range 70-120%, with relative standard deviation lower than 10% at 0.030 mg kg(-1) spiking level for most pesticides. LODs ranged 0.001-0.003 mg kg(-1), while LOQs ranged 0.004-0.009 mg kg(-1). The proposed method was successfully applied analyzing pesticide residues in real carp and sturgeon muscle samples; detectable pesticide residues were observed, but in all of the cases contamination level was lower than the default maximum residue levels (MRLs) set by the European Union (EU), Regulation (EC) N 396/2005. PMID:25074831

Molina-Ruiz, Juan Manuel; Cieslik, Ewa; Cieslik, Iwona; Walkowska, Izabela

2015-01-01

363

FAS Expression and Apoptosis in the Fish Parasite Ichthyophthirus  

Technology Transfer Automated Retrieval System (TEKTRAN)

Fish that survive an infection by Ichthyophthirius multifiliis (Ich) develop antibodies that immobilize and kill Ich theronts. Apoptosis of I. multifiliis theronts was caused by cutaneous antibody from channel catfish immune to Ich. The mechanism for cutaneous antibody to induce apoptosis of theron...

364

Increased Apoptosis During Neonatal Brain Development Underlies the Adult Behavioral  

E-print Network

apoptosis pathway. Peg3 inactivation in neuronal cell culture lines inhibits P53 mediated apoptosis, which in a number of developing hypothalamic and basal forebrain struc- tures and is a component of the P53 and maternal behaviors, oxytocin neuron number, metabolic homeo- stasis and growth. Peg3 is expressed

Champagne, Frances A.

365

Interferon-? Primes Macrophages for Lipopolysaccharide-Induced Apoptosis  

Microsoft Academic Search

Apoptosis plays an important role in generating and maintaining an effective immune system. Many pathogens can perturb the homeostasis of the immune system by either inducing or suppressing cell death of immune cells. Using bovine macrophages as a model, we found that interferon-?, one of the host?s responses to viral infection, can prime macrophages for activation-induced apoptosis. Exposure of bovine

B. Adler; H. Adler; T. W. Jungi; E. Peterhans

1995-01-01

366

Mitochondrion-mediated apoptosis induced by photofrin-PDT  

NASA Astrophysics Data System (ADS)

Apoptosis is an important cellular event that plays a key role in pathogeny and therapy of many diseases. The mechanisms of the initiation and regulation of PDT-induced apoptosis are complex. Some PDT-associated apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum (ER). In order to determine the apoptosis pathway induced by Photofrin-PDT, we used fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to monitor the dynamics of caspase-3 activation after PDT treatment and also measured caspase-8 activity. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes after PDT treatment. This was followed by mitochondrial membrane potential (??m), cytochrome c release, caspase-9 activity, caspase-3 activity and apoptosis. After PDT treatment, caspase-3 was activated rapidly while caspase-8 remained inactivated. Our results indicated that PDT-induced apoptosis was initiated from mitochondria pathway and independent of caspase-8 activation. The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. PDT-induced apoptosis is directly initiated from mitochondria pathway and not involved in the death receptors-dependent pathway. Our results demonstrated that FRET could be an effective tool to determine PDT-induced apoptosis and other cell death mechanism.

Wu, Yunxia; Xing, Da

2007-05-01

367

Apoptosis, programmed cell death and the hypersensitive response  

Microsoft Academic Search

Apoptosis is typically a morphologically identifiable form of programmed cell death in mammals that is regulated by genes with homologues in other animal Phyla. Although both plants and fungal plant pathogens exhibit forms of developmental programmed cell death, demonstrated morphological or genetic homologies with mammalian apoptosis are still generally lacking. Because of its ubiquity and the involvement of signal transduction

Michèle C. Heath

1998-01-01

368

Shear stress inhibits apoptosis of human endothelial cells  

Microsoft Academic Search

Physiological levels of shear stress alter the genetic program of cultured endothelial cells and reduce endothelial cell turnover in vivo. To test the hypothesis that shear stress interferes with programmed cell death, apoptosis was induced in human umbilical venous endothelial cells by growth factor withdrawal or incubation with tumor necrosis factor ?(TNF?) for 18 h. Apoptosis was quantified by ELISA

Stefanie Dimmeler; Judith Haendeler; Volker Rippmann; Michael Nehls; Andreas M. Zeiher

1996-01-01

369

The triterpenoid CDDO induces apoptosis in refractory CLL B cells  

Microsoft Academic Search

Chronic lymphocytic leukemia (CLL) cells develop chemo-resistance over time. Most anticancer agents function through induc- tion of apoptosis, and therefore resis- tance against these agents is likely to be caused by selection for CLL cells with defects in the particular apoptosis path- way that is triggered by these drugs. Anticancer agents that function through alternative apoptotic pathways might therefore be

Irene M. Pedersen; Shinichi Kitada; Aaron Schimmer; Youngsoo Kim; Juan M. Zapata; Lula Charboneau; Laura Rassenti; Michael Andreeff; Frank Bennett; Michael B. Sporn; Lance D. Liotta; Thomas J. Kipps; John C. Reed

2002-01-01

370

Constitutive apoptosis in equine peripheral blood neutrophils in vitro  

PubMed Central

The aim of this study was to characterise constitutive apoptosis in equine peripheral blood neutrophils, including assessment of factors that potentially modulate neutrophil survival through alteration of the rate of constitutive apoptosis. Cells underwent spontaneous time-dependent constitutive apoptosis when aged in culture for up to 36?h, developing the structural and functional features of apoptosis observed in many cell types, including human neutrophils. Neutrophils undergoing apoptosis also had diminished zymosan activated serum (ZAS)-stimulated chemiluminescence, but maintained responsiveness to phorbol myristate acetate (PMA). The constitutive rate of equine neutrophil apoptosis was promoted by lipopolysaccharide (LPS), tumour necrosis factor ? and phagocytosis of opsonised ovine erythrocytes, while it was inhibited by dexamethasone and ZAS (a source of C5a). Formyl-Met-Leu-Phe, leukotriene B4, platelet activating factor and PMA had no demonstrable effect on equine neutrophil apoptosis. There was a difference between equine and human neutrophil apoptosis in response to LPS and the time-dependence of the response to dexamethasone. PMID:25239298

Brazil, Timothy J.; Dixon, Padraic M.; Haslett, Christopher; Murray, Joanna; McGorum, Bruce C.

2014-01-01

371

Patterns of Proliferation and Apoptosis during Murine Hair Follicle Morphogenesis  

Microsoft Academic Search

In this study, we have correlated cutaneous apoptosis and proliferation in neonatal mice during hair follicle morphogenesis. We have applied a novel triple- staining technique that uses Ki67 immunoreactivity as a marker of proliferation as well as TUNEL and Hoechst 33342 staining as apoptosis markers. We have also assessed the immunoreactivity of interleukin-1?-converting enzyme, caspase 1, a key enzyme in

Markus Magerl; Desmond J. Tobin; Sven Müller-Röver; Evelin Hagen; Gerd Lindner; Ian A. McKay; Ralf Paus

2001-01-01

372

The mitochondrion in apoptosis: how Pandora's box opens  

Microsoft Academic Search

There is widespread agreement that mitochondria have a function in apoptosis, but the mechanisms behind their involvement remain controversial. Here we suggest that opening of a multiprotein complex called the mitochondrial permeability transition pore complex is sufficient (and, usually, necessary) for triggering apoptosis.

Naoufal Zamzami; Guido Kroemer

2001-01-01

373

Caspases in apoptosis and beyond J Li and J Yuan  

E-print Network

of the Caenorhabditis elegans programmed cell death gene product, CED-3, with human caspase-1 in 1993 triggered; programmed cell death Overview of apoptosis The term `apoptosis' was coined by Kerr, Wyllie and Currie the knowledge obtained from the studies of programmed cell death in the nematode Caenorhabditis elegans first

374

Molecular failure of apoptosis: inappropriate cell survival and mutagenesis?  

PubMed

Since cell death by apoptosis is achieved through complex interactions between numerous molecular components, cells may fail to die when stimulated because of molecular abnormalities in the apoptosis pathway or in its control mechanisms. Such inappropriate cell survival is well established when apoptosis is suppressed by elevated expression of bcl-2, at least for some cell types. Many cells undergo apoptosis at moderate levels of DNA damage and suppression of such apoptosis might be expected to increase the rate of mutation because of the persistence of cells with damaged DNA. We and others have now confirmed this prediction in bcl-2 transfected cells. Suppression of the apoptosis pathway can only lead to inappropriate cell survival if it relates to events before the cell becomes committed to die. We have analyzed this question for agents that inhibit the caspases, the site-specific proteases which form the biochemical core of the process of apoptosis. We have shown that inhibition of certain caspases does lead to the survival of Jurkat human T-cells induced to undergo Fas-mediated apoptosis. PMID:10022300

Williams, G T; Critchlow, M R; Hedge, V L; O'Hare, K B

1998-12-28

375

Changes in apoptosis of human polymorphonuclear granulocytes with aging  

Microsoft Academic Search

Many alterations with aging occur at the cellular and organic levels in the immune system ultimately leading to a decrease in the immune response. Our aim in the present work was to study apoptosis of polymorphonuclear granulocytes (PMN) with aging under various stimulations since apoptosis might play an important role in several pathologies encountered with aging. The PMN of healthy

T Fülöp Jr; C Fouquet; P Allaire; N Perrin; G Lacombe; J Stankova; M Rola-Pleszczynski; D Gagné; J. R Wagner; A Khalil; G Dupuis

1997-01-01

376

Serial killers: ordering caspase activation events in apoptosis  

Microsoft Academic Search

Caspases participate in the molecular control of apoptosis in several guises; as triggers of the death machinery, as regulatory elements within it, and ultimately as a subset of the effector elements of the machinery itself. The mammalian caspase family is steadily growing and currently contains 14 members. At present, it is unclear whether all of these proteases participate in apoptosis.

EA Slee; C Adrain; SJ Martin

1999-01-01

377

Osteocyte Apoptosis Is Mechanically Regulated and Induces Angiogenesis In Vitro  

E-print Network

Osteocyte Apoptosis Is Mechanically Regulated and Induces Angiogenesis In Vitro Wing-Yee Cheung,1 online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jor.21283 ABSTRACT: Osteocyte associationbetweenfluidflow andosteocyte apoptosis,osteocyte-like MLO-Y4 cellsweresubjectedto either oscillatoryfluidflow (10

Simmons, Craig A.

378

Helicobacter pylori vacuolating toxin A and apoptosis  

PubMed Central

VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to the sphingomyelin of lipid rafts. At least partially, binding to the cells is facilitated by different receptor proteins. VacA is internalized by a clathrin-independent mechanism and initially accumulates in GPI-anchored proteins-enriched early endosomal compartments. Together with early endosomes, VacA is distributed inside the cells. Most of the VacA is eventually contained in the membranes of vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low conductivity with a preference for chloride ions. In parallel, a significant fraction of VacA can be transferred from endosomes to mitochondria in a process involving direct endosome-mitochondria juxtaposition. Inside the mitochondria, VacA accumulates in the mitochondrial inner membrane, probably forming similar chloride channels as observed in the vacuoles. Import into mitochondria is mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of the mitochondrial membrane potential, recruitment of Bax and Bak, and release of cytochrome c. PMID:22044628

2011-01-01

379

Evolution of the Animal Apoptosis Network  

PubMed Central

The number of available eukaryotic genomes has expanded to the point where we can evaluate the complete evolutionary history of many cellular processes. Such analyses for the apoptosis regulatory networks suggest that this network already existed in the ancestor of the entire animal kingdom (Metazoa) in a form more complex than in some popular animal model organisms. This supports the growing realization that regulatory networks do not necessarily evolve from simple to complex and that the relative simplicity of these networks in nematodes and insects does not represent an ancestral state, but is the result of secondary simplifications. Network evolution is not a process of monotonous increase in complexity, but a dynamic process that includes lineage-specific gene losses and expansions, protein domain reshuffling, and emergence/reemergence of similar protein architectures by parallel evolution. Studying the evolution of such networks is a challenging yet interesting subject for research and investigation, and such studies on the apoptosis networks provide us with interesting hints of how these networks, critical in so many human diseases, have developed. PMID:23457257

Zmasek, Christian M.; Godzik, Adam

2013-01-01

380

Apoptosis: Calling Time on Apoptosome Activity  

NSDL National Science Digital Library

Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a “molecular timer” that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may enable cells to prevent low amounts of apoptosome activation from spiraling out of control unless sufficient numbers of apoptosomes are assembled within a particular time window, which would drive full-blown caspase activation and apoptosis.

Colin Adrain (Cambridge; Medical Research Council Laboratory of Molecular Biology REV)

2009-10-06

381

Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis  

PubMed Central

AIM: To assess the anti-cancer effect of lobaplatin on human gastric cancer cells, and to explore the underlying molecular mechanisms. METHODS: The human gastric cancer cell lines MKN-28, AGS and MKN-45 were used. The cytotoxicity of lobaplatin was detected using an MTS cell proliferation assay. Flow cytometry was used to detect cell apoptosis using Annexin V-FITC Apoptosis Detection Kit. The expression of apoptosis-regulated genes was examined at the protein level using Western blot. RESULTS: Lobaplatin inhibited the proliferation of human gastric cancer cells and induced apoptosis, which may be associated with the up-regulation of Bax expression, poly(ADP-ribose) polymerase (PARP) cleavage, p53 expression and the reduction of Bcl-2 expression. CONCLUSION: The cytotoxicity of lobaplatin may be due to its ability of inducing apoptosis of gastric cancer cells, which would support the potential use of lobaplatin for the therapy of gastric cancer. PMID:25516654

Yin, Chu-Yang; Lin, Xiao-Lin; Tian, Lei; Ye, Ming; Yang, Xin-Ying; Xiao, Xiu-Ying

2014-01-01

382

Melanocytorrhagy and apoptosis in vitiligo: connecting jigsaw pieces.  

PubMed

Vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and follicular reservoir. The mechanism of melanocyte disappearance has never been clearly understood. This review discussed the data supporting the theory of melanocytorrhagy and apoptosis as one of the primary defects underlying melanocyte loss. Theory of melanocytorrhagy proposes that non-segmental vitiligo is a primary melanocytorrhagic disorder with altered melanocyte responses to friction and possibly other types of stress, inducing their detachment and subsequent transepidermal loss. Melanocytes detachment induces apoptosis whereas adherence to basement membrane suppresses apoptosis. The study of apoptosis, mechanisms of its induction, and the ways to block apoptosis is one possible way to find both the causes of depigmentation and medications to prevent its progression. PMID:22199056

Kumar, Ravinder; Parsad, Davinder

2012-01-01

383

microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway.  

PubMed

microRNA-29b (miR-29b) is known to be associated with TGF-?-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 induced-fibrogenesis, concomitant with decreased expression of ?-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3'UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed ?-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b. PMID:25356754

Wang, Jia; Chu, Eagle S H; Chen, Hai-Yong; Man, Kwan; Go, Minnie Y Y; Huang, Xiao Ru; Lan, Hui Yao; Sung, Joseph J Y; Yu, Jun

2015-03-30

384

Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis.  

PubMed

Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. Infection with high-risk human papillomaviruses (HPV) leads to development of cervical carcinoma, predominantly through the action of viral oncoproteins E6 and E7. The present study aims at analyzing the antitumor and antiviral properties of curcumin, on HPV associated cervical cancer cells. Our findings indicate curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent and time-dependent manner. The cytotoxic activity was selectively more in HPV16 and HPV18 infected cells compared to non-HPV infected cells. Balance between tumor cell proliferation and spontaneous cell death via apoptosis had an important role in regulation of tumor cell growth. Curcumin-induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin also selectively inhibited expression of viral oncogenes E6 and E7, evident from RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin. Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a gene regulated by NFkappaB. Binding of AP-1, an indispensable component for efficient epithelial tissue-specific gene expression of HPV was also selectively down regulated by curcumin. These results provide attractive data for the possible use of curcumin in the management of HPV associated tumors. PMID:16526022

Divya, Chandrasekhar S; Pillai, M Radhakrishna

2006-05-01

385

Lymphocytes apoptosis in patients with acute exacerbation of asthma.  

PubMed Central

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum. Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anti-cytokine antibodies. Anti-TNF-alpha antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-alpha acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation. PMID:10704078

Hamzaoui, A; Hamzaoui, K; Salah, H; Chabbou, A

1999-01-01

386

Modulation of apoptosis by mitochondrial uncouplers: apoptosis-delaying features despite intrinsic cytotoxicity  

Microsoft Academic Search

Disruption of mitochondrial electron transport and opening of the so-called mitochondrial permeability transition pores (PTPs) are early events in apoptotic cell death and may be caused by the uncoupler of mitochondrial oxidation and phosphorylation, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). We investigated the cellular toxicity of FCCP in HL60 and CCRF-CEM cells alone or in combination with the known apoptosis inducers such

Oliver J Stoetzer; Alexei Pogrebniak; Renate Pelka-Fleischer; Max Hasmann; Wolfgang Hiddemann; Volkmar Nuessler

2002-01-01

387

Enzymatic assays for probing mitochondrial apoptosis.  

PubMed

Isolated mitochondria are an invaluable analytical tool to probe mitochondrial function and evaluate apoptosis induction via the so-called mitochondrial pathway. Irrespective of their tissue origin (e.g., heart, liver, muscle, brain), these organelles participate actively to cell and life decision by producing energy for cell metabolism, but also by undergoing a lethal and irreversible mitochondrial membrane permeabilization (MMP) in stress and pathological conditions. MMP consequences consist, at least in part, in loss of mitochondrial transmembrane potential (??m), matrix swelling, arrest of respiration and ATP production, and cytochrome c release from the intermembrane space to the cytosol. These parameters can be evaluated in vitro via several miniaturized assays, which have tremendous applications in the field of pharmacology, toxicology, diagnosis, as well as drug discovery. PMID:25634292

Wang, Zhenyu; Nicolas, Claire; Fischmeister, Rodolphe; Brenner, Catherine

2015-01-01

388

CARD games in apoptosis and immunity  

PubMed Central

A bewildering array of proteins containing the caspase recruitment domain (CARD) have now been identified. Previously, CARD–CARD interactions have been shown to be involved in the assembly of protein complexes that promote caspase processing and activation in the context of apoptosis. However, as the family of CARD-containing proteins has grown, it has become apparent that the majority of these proteins do not recruit caspases or promote caspase activation. Instead, many participate in NF-?B signalling pathways associated with innate or adaptive immune responses. Here, we suggest a simplified classification of the CARD proteins based upon their domain structures and discuss the divergent roles of these proteins in the context of host defence. PMID:12101092

Bouchier-Hayes, Lisa; Martin, Seamus J.

2002-01-01

389

The Tangled Circuitry of Metabolism and Apoptosis  

PubMed Central

For single cell organisms, nutrient uptake and metabolism are at the crux of their most basic decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate within multicellular organisms is also influenced by metabolism; recent studies, triggered in part be an interest tumor metabolism, are beginning to illuminate the mechanisms through which proliferation, death, and metabolism are intertwined. In particular, work on Bcl-2 family proteins suggests that the signaling pathways governing metabolism and apoptosis are inextricably linked. Here, we review the crosstalk between these pathways, emphasizing recent work that illustrates the emerging dual nature of several core apoptotic proteins in regulating both metabolism and cell death. PMID:23395270

Andersen, Joshua L.; Kornbluth, Sally

2013-01-01

390

Vasopressin decreases neuronal apoptosis during cardiopulmonary resuscitation  

PubMed Central

The American Heart Association and the European Resuscitation Council recently recommended that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopulmonary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Jun N-terminal kinase and p38 expression were significantly decreased in the hippocampus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation. PMID:25206865

Ma, Chi; Zhu, Zhe; Wang, Xu; Zhao, Gang; Liu, Xiaoliang; Li, Rui

2014-01-01

391

Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor  

PubMed Central

Background Nasopharyngeal carcinoma (NPC) has a high incidence rate in Southern China. Although there are conventional therapies, the side effects and toxicities are not always tolerable for patients. Recently, the tumoricidal effect of ginsenosides on different cancer cells has been studied. This study aims to investigate the anti-cancer effect of ginsenosides on NPC cells and their underlying mechanism. Methods The cytotoxicity of ginsenosides on NPC cell line HK-1 was measured by MTT assay. Apoptosis was detected by propidium iodide staining followed by flow cytometry. A xenograft tumor model was established by injecting nude mice with HK-1 cells. The activation of caspases and apoptosis-inducing factor (AIF) were evaluated by Western blot analysis. Nuclear translocation of AIF was also studied by immunofluorescence staining. Mitochondrial membrane potential was measured by JC-1 dye using flow cytometry. Results Four ginsenosides, 20 (S)-Rh2, compound K (CK), panaxadiol (PD) and protopanaxadiol (PPD), induced apoptotic cell death in HK-1 cells in a concentration-dependent manner. CK inhibited HK-1 xenograft tumor growth most extensively and depleted mitochondrial membrane potential depolarization and induced translocation of AIF from cytoplasm to nucleus in HK-1 cells. In addition, depletion of AIF by siRNA abolished CK-induced HK-1 cell death. Conclusion Ginsenoside CK-induced apoptosis of HK-1 cells was mediated by the mitochondrial pathway and could significantly inhibit tumor growth in vivo. PMID:24690317

2014-01-01

392

Apoptosis and the systolic dysfunction in congestive heart failure. Story of apoptosis interruptus and zombie myocytes.  

PubMed

Although previously it was believed that apoptosis could not occur in the terminally differentiated tissue, such as adult heart muscle cells, recent studies in endomyocardial biopsies from patients with dilated cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histologic evidence of apoptosis. Whereas neurohormonal activation during heart failure leads to compensatory hemodynamic alterations, coupled with ventricular dilatation, it induces transcription factors and myocyte hypertrophy. Persistent growth stimulation in terminally differentiated cells may lead paradoxically to apoptotic cell death. The apoptosis in cardiomyopathic hearts is associated with cytochrome c release from mitochondria to cytoplasm and activation of proteolytic caspase-8 and -3. Although the caspases are duly processed, the fragmentation of the nuclear proteins (including DNA) is completed less frequently, and only a variable degree of fragmentation of cytoplasmic proteins (including contractile proteins) is observed. It is hypothesized that release of cytochrome c from mitochondria should interfere with energy production and lead to functional impairment and variable loss of contractile proteins in a living heart muscle cell should contribute to systolic dysfunction. Because a nuclear blueprint is retained, however, the dysfunctional cell may continue to exist and in favorable conditions, such as with LVAD support, the apoptotic process may subside. Potential feasibility of reversal of heart failure should renew efforts to develop more targeted pharmaceutical intervention within the apoptotic cascade and allow newer paradigm for the management of heart failure. PMID:11787805

Narula, J; Arbustini, E; Chandrashekhar, Y; Schwaiger, M

2001-02-01

393

Retinoids induce Nur77-dependent apoptosis in mouse thymocytes.  

PubMed

Nur77 is a transcription factor, which plays a determinant role in mediating T cell receptor-induced cell death of thymocytes. In addition to regulation of transcription, Nur77 contributes to apoptosis induction by targeting mitochondria, where it can convert Bcl-2, an anti-apoptotic protein into a proapoptotic molecule. Previous studies have demonstrated that retinoids are actively produced in the mouse thymus and can induce a transcription-dependent apoptosis in mouse thymocytes. Here we show that retinoic acids induce the expression of Nur77, and retinoid-induced apoptosis is completely dependent on Nur77, as retinoids were unable to induce apoptosis in Nur77 null thymocytes. In wild-type thymocytes retinoids induced enhanced expression of the apoptosis-related genes FasL, TRAIL, NDG-1, Gpr65 and Bid, all of them in a Nur77-dependent manner. The combined action of these proteins led to Caspase 8-dependent Bid cleavage in the mitochondria. In addition, we could demonstrate the Nur77-dependent induction of STAT1 leading to enhanced Bim expression, and the mitochondrial translocation of Nur77 leading to the exposure of the Bcl-2/BH3 domain. The retinoid-induced apoptosis was dependent on both Caspase 8 and STAT1. Our data together indicate that retinoids induce a Nur77-dependent cell death program in thymocytes activating the mitochondrial pathway of apoptosis. PMID:25576519

Kiss, Beáta; Tóth, Katalin; Sarang, Zsolt; Garabuczi, Éva; Szondy, Zsuzsa

2015-03-01

394

Apoptosis of human intestinal epithelial cells after bacterial invasion.  

PubMed Central

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers. PMID:9819367

Kim, J M; Eckmann, L; Savidge, T C; Lowe, D C; Witthöft, T; Kagnoff, M F

1998-01-01

395

Viruses, apoptosis, and neuroinflammation--a double-edged sword.  

PubMed

Apoptosis, or programmed cell death, is a fundamental and widespread cell biological process that is distinct from cell necrosis and can be induced by a wide variety of stimuli including viral infections. Apoptosis may occur via either the intrinsic or extrinsic pathways and confers several advantages to the virally infected host including the prevention of further viral propagation and the potential inhibition and resolution of inflammatory processes. Several viruses have been shown to have the capacity to induce apoptosis in susceptible cells including herpes simplex virus, Varicella-zoster virus, rabies virus, human immunodeficiency virus, and reovirus. Apoptosis has also been observed in human African trypanosomiasis which is an infection caused by a protozoan parasite. The mechanisms leading to apoptosis may differ depending on the type of infection. Apoptosis has been reported in several neurodegenerative diseases and also psychiatric disorders but the true clinical significance of such observations is not certain, and, though interesting, it is very difficult to ascribe causation in these conditions. The presence of inflammation in the central nervous system in any neurological condition, including those associated with a viral infection, is not necessarily an absolute marker of serious disease and the notion of 'good' versus 'bad' inflammation is considered to be valid in some circumstances. The precise relationship between viruses, apoptosis, and inflammation is viewed as a complex one requiring further investigation to unravel and understand its nature. PMID:25604493

Kennedy, Peter G E

2015-02-01

396

Role of Siglec-7 in Apoptosis in Human Platelets  

PubMed Central

Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on ? granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (??m) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

2014-01-01

397

Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis  

PubMed Central

Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression. PMID:22567408

Chakraborty, Jayashree Bagchi; Oakley, Fiona; Walsh, Meagan J.

2012-01-01

398

Lysine methyltransferase Smyd2 suppresses p53-dependent cardiomyocyte apoptosis.  

PubMed

Apoptosis, or programmed cell death, is an essential physiological process for proper embryogenesis as well as for homeostasis during aging. In addition, apoptosis is one of the major mechanisms causing cell loss in pathophysiological conditions such as heart failure. Thus, inhibition of apoptosis is an important approach for preventive and therapeutic strategies. Here we show that the histone 3 lysine 4- and lysine 36-specific methyltransferase Smyd2 acts as an endogenous antagonistic player of p53-dependent cardiomyocyte apoptosis. Smyd2 protein levels were significantly decreased in cardiomyocytes upon cobalt chloride-induced apoptosis or myocardial infarction, while p53 expression was enhanced. siRNA-mediated knockdown of Smyd2 in cultured cardiomyocytes further enhanced cobalt chloride-induced cardiomyocyte apoptosis. In contrast, Smyd2 overexpression resulted in marked methylation of p53 and prevented its accumulation as well as apoptotic cell death in an Hsp90-independent manner. Moreover, overexpression, of Smyd2, but not Smyd2Y240F lacking a methyl transferase activity, significantly rescued CoCl2-induced apoptosis in H9c2 cardioblasts. Finally, Smyd2 cardiomyocyte-specific deletion in vivo promoted apoptotic cell death upon myocardial infarction, which correlated with enhanced expression of p53 and pro-apoptotic Bax. Collectively, our data indicate Smyd2 as a cardioprotective protein by methylating p53. PMID:25014164

Sajjad, Amna; Novoyatleva, Tatyana; Vergarajauregui, Silvia; Troidl, Christian; Schermuly, Ralph T; Tucker, Haley O; Engel, Felix B

2014-11-01

399

Recovering Drug-Induced Apoptosis Subnetwork from Connectivity Map Data  

PubMed Central

The Connectivity Map (CMAP) project profiled human cancer cell lines exposed to a library of anticancer compounds with the goal of connecting cancer with underlying genes and potential treatments. Since the therapeutic goal of most anticancer drugs is to induce tumor-selective apoptosis, it is critical to understand the specific cell death pathways triggered by drugs. This can help to better understand the mechanism of how cancer cells respond to chemical stimulations and improve the treatment of human tumors. In this study, using CMAP microarray data from breast cancer cell line MCF7, we applied a Gaussian Bayesian network modeling approach and identified apoptosis as a major drug-induced cellular-pathway. We then focused on 13 apoptotic genes that showed significant differential expression across all drug-perturbed samples to reconstruct the apoptosis network. In our predicted subnetwork, 9 out of 15 high-confidence interactions were validated in the literature, and our inferred network captured two major cell death pathways by identifying BCL2L11 and PMAIP1 as key interacting players for the intrinsic apoptosis pathway and TAXBP1 and TNFAIP3 for the extrinsic apoptosis pathway. Our inferred apoptosis network also suggested the role of BCL2L11 and TNFAIP3 as “gateway” genes in the drug-induced intrinsic and extrinsic apoptosis pathways.

Yu, Jiyang; Putcha, Preeti; Silva, Jose M.

2015-01-01

400

Apoptosis of circulating lymphocytes during pediatric cardiac surgery  

NASA Astrophysics Data System (ADS)

There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.

2006-02-01

401

Rapid isolation and identification of minor natural products by LC-MS, LC-SPE-NMR and ECD: isoflavanones, biflavanones and bisdihydrocoumarins from Ormocarpum kirkii.  

PubMed

The combination of the hyphenated techniques LC-MS and LC-SPE-NMR constitutes a powerful platform for the rapid isolation and identification of minor components from natural sources. Electronic circular dichroism (ECD) is a useful tool to determine the absolute configuration of small quantities of chiral molecules. In order to search for minor constituents present in an Ormocarpum kirkii extract, these techniques were applied for the separation and structure elucidation of a series of isoflavanones, biflavanones and biscoumarins. After optimization of chromatographic conditions and subsequent isolation, MS and 1D and 2D NMR data were collected. Experimental and calculated ECD spectra were used in conjunction with NMR data to confirm the absolute configuration of these compounds. Eight compounds were identified for the first time and six have been previously reported. The present approach offers a strategy for accelerating research on natural products. PMID:22575670

Xu, Yong-Jiang; Foubert, Kenn; Dhooghe, Liene; Lemière, Filip; Maregesi, Sheila; Coleman, Christina M; Zou, Yike; Ferreira, Daneel; Apers, Sandra; Pieters, Luc

2012-07-01

402

HPLC-SPE-NMR characterization of major metabolites in Salvia fruticosa Mill. extract with antifungal potential: relevance of carnosic acid, carnosol, and hispidulin.  

PubMed

Plant pathogenic fungi are considered of significant economic importance for adversely affecting both quantitatively and qualitatively fresh and processed produce. Extracts of Salvia fruticosa were initially screened for their antifungal activity, and the ethyl acetate fraction, being the most active, was further analyzed using HPLC-SPE-NMR hyphenation. The methoxylated flavones hispidulin, salvigenin, and cirsimaritin and the diterpenes carnosic acid, carnosol, and 12-methoxycarnosic acid were identified as the major components of the extract. In addition, the concentration levels of all identified components were determined using q-NMR. The antifungal activity of the crude extract and selected phytochemicals was estimated against the fungal species Aspergillus tubingensis, Botrytis cinerea, and Penicillium digitatum. The estimated MIC and MFC values of the ethyl acetate extract of S. fruticosa, as well as three of its major constituents, carnosic acid, carnosol, and hispidulin, support their antifungal activity, especially against B. cinerea and P. digitatum, suggesting their potential use in food and agricultural systems. PMID:25537192

Exarchou, Vassiliki; Kanetis, Loukas; Charalambous, Zenovia; Apers, Sandra; Pieters, Luc; Gekas, Vassilis; Goulas, Vlasios

2015-01-21

403

Development, validation, and uncertainty measurement of multi-residue analysis of organochlorine and organophosphorus pesticides using pressurized liquid extraction and dispersive-SPE techniques.  

PubMed

Simple and efficient multi-residue analytical methods were developed and validated for the determination of 13 organochlorine and 17 organophosphorous pesticides from soil, spinach and eggplant. Techniques namely accelerated solvent extraction and dispersive SPE were used for sample preparations. The recovery studies were carried out by spiking the samples at three concentration levels (1 limit of quantification (LOQ), 5 LOQ, and 10 LOQ). The methods were subjected to a thorough validation procedure. The mean recovery for soil, spinach and eggplant were in the range of 70-120% with median CV (%) below 10%. The total uncertainty was evaluated taking four main independent sources viz., weighing, purity of the standard, GC calibration curve and repeatability under consideration. The expanded uncertainty was well below 10% for most of the pesticides and the rest fell in the range of 10-20%. PMID:21210211

Sanyal, Doyeli; Rani, Anita; Alam, Samsul; Gujral, Seema; Gupta, Ruchi

2011-11-01

404

Development of a SPE-UHPLC-MS/MS methodology for the determination of non-steroidal anti-inflammatory and analgesic pharmaceuticals in seawater.  

PubMed

An analytical methodology for the simultaneous determination of seven pharmaceuticals and two metabolites belonging to the non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics therapeutic groups was developed based on off-line solid-phase extraction and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (SPE-UHPLC-MS/MS). Extraction conditions were optimized taking into account parameters like sorbent material, sample volume and sample pH. Method detection limits (MDLs) ranging from 0.02 to 8.18ng/L were obtained. This methodology was successfully applied to the determination of the selected pharmaceuticals in seawater samples of Atlantic Ocean in the Northern Portuguese coast. All the pharmaceuticals have been detected in the seawater samples, with pharmaceuticals like ibuprofen, acetaminophen, ketoprofen and the metabolite hydroxyibuprofen being the most frequently detected at concentrations that can reach some hundreds of ng/L. PMID:25002040

Paíga, Paula; Loli?, Aleksandar; Hellebuyck, Floris; Santos, Lúcia H M L M; Correia, Manuela; Delerue-Matos, Cristina

2015-03-15

405

1 S.R. REEVES, D.G. HILL, R.L. TINER, P.A. BASTIAN, M.W. CONWAY & S. MOHAGHEGH SPE 55627 Copyright 1999, Society of Petroleum Engineers Inc.  

E-print Network

1999, Society of Petroleum Engineers Inc. This paper was prepared for presentation at the 1999 SPE by the author(s). Contents of the paper, as presented, have not been reviewed by the Society of Petroleum reflect any position of the Society of Petroleum Engineers, its officers, or members. Papers presented

Mohaghegh, Shahab

406

Page 352 Courses: Nursing (NURS) Sonoma State University 2010-2011 Catalog nurS 313 BACCAlAureAte nurSinG perSpeCtiVeS ii (4)  

E-print Network

Page 352 Courses: Nursing (NURS) Sonoma State University 2010-2011 Catalog nurS 313 BACCAlAureAte nurSinG perSpeCtiVeS ii (4) Seminar, 4 hours. Application of baccalaureate nursing perspectives in childbearing and child-rearing families. Preventive and therapeutic aspects of nursing care for the pregnant

Ravikumar, B.

407

Courses: Nursing (NURS) Page 367Sonoma State University 2013-2014 Catalog nurS 313 BACCALAureAte nurSing perSpeCtiVeS ii (4)  

E-print Network

Courses: Nursing (NURS) Page 367Sonoma State University 2013-2014 Catalog nurS 313 BACCALAureAte nurSing perSpeCtiVeS ii (4) This course expands knowledge about the role of the professional nurse in society by exploring leadership and advocacy as integral components of professional nursing. It examines

Ravikumar, B.

408

spe433-02 page 27 Ernst, W.G., Hacker, B.R., and Liou, J.G., 2007, Petrotectonics of ultrahigh-pressure crustal and upper-mantle rocks--Implications for Phanerozoic collisional  

E-print Network

spe433-02 page 27 27 Ernst, W.G., Hacker, B.R., and Liou, J.G., 2007, Petrotectonics of ultrahigh of Geological and Environmental Sciences, Stanford University, Stanford, California 94305-2115, USA B.R. Hacker

Hacker, Bradley R.

409

SPE Combined with HPLC-APCI-MS Analysis of Pesticides in Water: Method Performance and Application in a Reconnaissance Survey of Residues in Drinking Water in Greater Cairo (Egypt)  

Technology Transfer Automated Retrieval System (TEKTRAN)

The portability, ease of use, and potential to enhance analyte stability makes solid-phase extraction (SPE) an attractive technique for extracting water samples collected for pesticide residue analysis prior to their shipment to analytical laboratories. The technique is especially valuable when samp...

410

Human cytomegalovirus IE1 and IE2 proteins block apoptosis.  

PubMed Central

Human cytomegalovirus-infected fibroblasts are resistant to the induction of apoptosis by superinfection with a mutant adenovirus unable to produce the viral E1B 19-kDa protein that normally causes an E1A protein-mediated apoptotic response. Two cytomegalovirus gene products that block apoptosis were identified. The IE1 and IE2 proteins each inhibit the induction of apoptosis by tumor necrosis factor alpha or by the E1B 19-kDa-protein-deficient adenovirus but not by irradiation with UV light. Our results suggest a new physiological role for the IE1 and IE2 proteins in the human cytomegalovirus replication cycle. PMID:7494309

Zhu, H; Shen, Y; Shenk, T

1995-01-01

411

Automated determination of venlafaxine in human plasma by on-line SPE-LC-MS/MS. Application to a bioequivalence study.  

PubMed

A new automated SPE-LC-ESI-MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction-monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25-200 ng/mL (r >0.997). The between-run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between-run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth-Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off-line liquid-liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6-103.4% for AUC(0-48 h) and 102.2-112.6% for C(max). Since both 90% CI for AUC(0-48 h) and C(max) were included in the 80-125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption. PMID:19212975

Suenaga, Eunice Mayumi; Ifa, Demian R; Cruz, Alessandro Carvalho; Pereira, Renata; Abib, Eduardo; Tominga, Mineko; Nakaie, Clovis Ryuichi

2009-02-01

412

Two novel zeolitic imidazolate frameworks (ZIFs) as sorbents for solid-phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples.  

PubMed

In this work, two novel zeolitic imidazolate framework (ZIF) materials, ZIF-7 and ZIF-11, were firstly introduced as solid-phase extraction (SPE) sorbents for PAHs efficient extraction and highly sensitive analysis in environmental water samples with high performance liquid chromatography (HPLC) coupled with fluorescence detection. ZIF-7 and ZIF-11 were successfully synthesized and characterized with SEM, FTIR, XRD and water contact angels, exhibiting unique and excellent stability, spatial structure and chemical composition, promising for environmental PAHs efficient enrichment through hydrophobic, ?-? and ?-complexation interactions. The topology effect on PAHs extraction was compared between ZIF-7 and ZIF-11, considering they have the same composition in metal ion (Zn(2+)) and organic linker, but differing spatial structures: ZIF-7 has a cubic structure, while ZIF-11 is a rhombic dodecahedron. At last, ZIF-11 with markedly better extraction efficiencies was selected for subsequent analysis. Under optimum extraction conditions such as sample volume, extraction time, desorption conditions, volume of organic modifier and salt concentration, a robust and highly efficient method based on ZIF-11 as a novel SPE sorbent has been successfully developed for environmental PAHs analysis. Satisfactory precision and accuracy ranging from 1-2.4 × 10(3) ng L(-1) as well as ultrasensitive detection limits of 0.08-1.6 ng L(-1) have been successfully achieved. Moreover, ZIF-11 extraction also exhibited high recoveries of 82.4-112.7% with relative standard deviations (RSDs) being less than 9% for PAHs in the environmental water samples. Therefore, our novel, convenient and efficient extraction method based on ZIF-11 as a sorbent is promising for applications in future trace-level environmental PAHs analyses. PMID:25209546

Hu, Huiping; Liu, Shengquan; Chen, Chunyan; Wang, Jianping; Zou, Ying; Lin, Lihua; Yao, Shouzhuo

2014-11-21

413

GCR and SPE organ doses in deep space with different shielding: Monte Carlo simulations based on the FLUKA code coupled to anthropomorphic phantoms  

NASA Astrophysics Data System (ADS)

Astronauts' exposure to space radiation is of high concern for long-term missions, especially for those in deep space such as possible travels to Mars. In these cases shielding optimization is a crucial issue, and simulations based on radiation transport codes and anthropomorphic model phantoms can be of great help. In this work the FLUKA Monte Carlo code was coupled with two anthropomorphic phantoms (a mathematical model and a "voxel" model) to calculate organ-averaged dose, dose equivalent and "biological dose" in the various tissues and organs following exposure to the August 1972 Solar Particle Event and to Galactic Cosmic Rays under different shielding conditions. The "biological dose" was characterized by the average number of induced "Complex Lesions" (CLs) per cell in a given organ or tissue, where CLs are clustered DNA breaks which can play an important role in chromosome aberration induction. Separate calculation of the contributions from secondary hadrons - in particular neutrons - with respect to primary particles allowed us to quantify the role played by nuclear interactions occurring in the shield and in the human body. Specifically for GCR, the contributions from the different components of the incident primary spectra were calculated separately as well. As expected, the SPE doses showed a dramatic decrease with increasing Al shielding. Furthermore, for SPEs internal organs received much lower doses with respect to skin, and nuclear interactions were found to be of minor importance. A 10 g/cm 2 Al storm shelter turned out to be sufficient to respect the NCRP limits for 30-days LEO missions in case of a SPE similar to the August 1972 event. In contrast with SPEs, GCR absorbed doses remained roughly constant with increasing Al shielding. The organ-averaged dose equivalent and biological dose showed a (slight) decrease starting from a shield thickness of 2 g/cm 2, probably due the lower LET of projectile fragments.

Ballarini, F.; Battistoni, G.; Cerutti, F.; Fassò, A.; Ferrari, A.; Gadioli, E.; Garzelli, M. V.; Mairani, A.; Ottolenghi, A.; Paretzke, H. G.; Parini, V.; Pelliccioni, M.; Pinsky, L.; Sala, P. R.; Scannicchio, D.; Trovati, S.; Zankl, M.

414

Stratospheric hydrogen peroxide (H2O2): Comparison between MIPAS observations and KASIMA model results with focus on the SPE 2003  

NASA Astrophysics Data System (ADS)

H, OH and HO2 (collectively called HOx) are fast-reacting radicals in the middle atmosphere. These radicals are efficient catalysts for destroying ozone and play an important role in atmospheric chemistry. An important reservoir gas for HOx is Hydrogen Peroxide (H2O2). For all these important species at the moment only few measurements exist, e.g. in-situ measurements in the troposphere, balloon and rocket measurements, few HOx measurements by aircraft, and global satellite measurements of OH and HO2 by Aura/MLS since 2005. We present results for H2O2 for global day and night measurements with the MIPAS instrument on the ESA satellite ENVISAT. We find is a strong annual cycle with high values for H2O2 in polar summer consitent with the strong coupling to HOx chemistry. We investigated in more detail the Solar Proton Event (SPE) that occurred in October/November 2003. During SPEs, precipitation of energetic protons into the polar atmosphere produces ions in the middle atmosphere which form, partly via ion-cluster-reactions, odd hydrogen (HOx ) and odd nitrogen (NOx ). Increased levels of HOx and NOx, in turn, depletes the ozone in the polar stratosphere and mesosphere. We present the results of our retrievals of H2O2 for this event and compare the observations with results of the KASIMA model which has been upgraded to handle the ionization of the atmosphere due to the SPE and subsequent chemical reactions due to the NOx/HOx enhancements.

Versick, S.

2009-04-01

415

Alymphoplasia ( aly )-type Nuclear Factor k B-inducing Kinase (NIK) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-associated Lymphatic Tissue System  

Microsoft Academic Search

Alymphoplasia ( aly ) mice, which carry a point mutation in the nuclear factor k B-inducing ki- nase (NIK) gene, are characterized by the systemic absence of lymph nodes and Peyer's patches, disorganized splenic and thymic architectures, and immunodeficiency. Another unique feature of aly\\/aly mice is that their peritoneal cavity contains more B1 cells than normal and aly\\/ 1 mice.

Sidonia Fagarasan; Reiko Shinkura; Tadashi Kamata; Fumiaki Nogaki; Koichi Ikuta; Kei Tashiro; Tasuku Honjo

416

High-throughput analytical techniques for multiresidue, multiclass determination of 653 pesticides and chemical pollutants in tea--Part III: Evaluation of the cleanup efficiency of an SPE cartridge newly developed for multiresidues in tea.  

PubMed

A comparative study was conducted over three stages on the cleanup efficiency of SPE cartridge Cleanert TPT, newly developed for multigroups of pesticide residues in tea. In Stage I, different SPE cartridges C18, graphite carbon black (GCB), primary secondary amine (PSA), and amino (NH2) were purchased and combined into 12 different sequences. Through the comparative test on cleanup efficiency of 84 representative pesticides in tea, Envi-Carb GCB + PSA with a good cleanup effect was selected. In Stage II, GC/MS test results from the comparative study of the extraction efficiency of 201 pesticides spiked into green tea and Woolong tea with Cleanert TPT and Envi-Carb + PSA SPE showed that average recoveries fell within 70-110% and RSD <20% for 193 and 184 pesticides, respectively, for green tea, accounting for 96.0 and 91.0% of the total number, respectively. GC/MS/MS test results also found 193 and 184 pesticides, respectively, meeting the recovery and RSD conditions, accounting for 96.0 and 91.5%, respectively, of the total number. For Woolong tea samples, GC/MS results showed that with Cleanert TPT and Envi-Carb + PSA SPE for cleanup, there were 192 and 177 pesticides, respectively, meeting the conditions, accounting for 95.5 and 88.1% of the total number, respectively. GC/MS/MS results demonstrated that there were 195 and 184 pesticides, respectively, meeting the conditions, accounting for 97.0 and 91.5% of the total number, respectively. It was seen that Cleanert TPT was superior to Envi-Carb + PSA in cleanup efficiency, whether for green or Woolong tea samples, or GC/MS or GC/MS/MS determination. In Stage III, 61104 results of the average content value of pesticides and RSD (two teas xtwo Youden pair concentrations x two kinds of SPE cartridges x two instruments x 19 tests x 201 pesticides) were derived from the 19 times stability tests over 3 months by paralleling three samples every 5 days via two instruments with two kinds of SPE cartridges for cleanup, respectively, against Youden Pair samples of the 201 incurred pesticides from green and Woolong teas. The statistical analysis found that detected values from the target pesticides of the incurred Youden pair samples showed no marked differences with cleanup by either Cleanert TPT or Envi-Carb + PSA, whether for green or Woolong tea, or G/IMS or G/IM/IMS. The test results using the two aforementioned kinds of SPE cleanup for above 93% pesticides had a tolerance less than 15%, which testifies that both cartridge cleanups met the requirement for pesticide residue analysis. PMID:24000765

Pang, Guo-Fang; Fan, Chun-Lin; Chang, Qiao-Ying; Li, Yan; Kang, Jian; Wang, Wen-Wen; Cao, Jing; Zhao, Yan-Bing; Li, Nan; Li, Zeng-Yin; Chen, Zong-Mao; Luo, Feng-Jian; Lou, Zheng-Yun

2013-01-01

417

Bench-to-bedside review: Apoptosis/programmed cell death triggered by traumatic brain injury  

PubMed Central

Apoptosis, or programmed cell death, is a physiological form of cell death that is important for normal embryologic development and cell turnover in adult organisms. Cumulative evidence suggests that apoptosis can also be triggered in tissues without a high rate of cell turnover, including those within the central nervous system (CNS). In fact, a crucial role for apoptosis in delayed neuronal loss after both acute and chronic CNS injury is emerging. In the current review we summarize the growing evidence that apoptosis occurs after traumatic brain injury (TBI), from experimental models to humans. This includes the identification of apoptosis after TBI, initiators of apoptosis, key modulators of apoptosis such as the Bcl-2 family, key executioners of apoptosis such as the caspase family, final pathways of apoptosis, and potential therapeutic interventions for blocking neuronal apoptosis after TBI. PMID:15693986

Zhang, Xiaopeng; Chen, Yaming; Jenkins, Larry W; Kochanek, Patrick M; Clark, Robert SB

2005-01-01

418

Caenorhabditis elegans caspase homolog CSP2 inhibits CED3 autoactivation and apoptosis in germ cells  

Microsoft Academic Search

In Caenorhabditis elegans, apoptosis in germ cells is mediated by the same core apoptotic machinery that controls apoptosis in somatic cells. These include the CED-3 caspase, the CED-3 activator CED-4, and the cell death inhibitor CED-9. However, germline apoptosis also differs from somatic apoptosis in its regulation. We found that CSP-3, a caspase homolog that blocks CED-3 autoactivation and apoptosis

X Geng; Q H Zhou; E Kage-Nakadai; Y Shi; N Yan; S Mitani; D Xue

2009-01-01

419

Mitochondrial apoptosis: killing cancer using the enemy within  

PubMed Central

Apoptotic cell death inhibits oncogenesis at multiple stages, ranging from transformation to metastasis. Consequently, in order for cancer to develop and progress, apoptosis must be inhibited. Cell death also plays major roles in cancer treatment, serving as the main effector function of many anti-cancer therapies. In this review, we discuss the role of apoptosis in the development and treatment of cancer. Specifically, we focus upon the mitochondrial pathway of apoptosis—the most commonly deregulated form of cell death in cancer. In this process, mitochondrial outer membrane permeabilisation or MOMP represents the defining event that irrevocably commits a cell to die. We provide an overview of how this pathway is regulated by BCL-2 family proteins and describe ways in which cancer cells can block it. Finally, we discuss exciting new approaches aimed at specifically inducing mitochondrial apoptosis in cancer cells, outlining their potential pitfalls, while highlighting their considerable therapeutic promise. PMID:25742467

Lopez, J; Tait, S W G

2015-01-01

420

CONFOCAL LASER SCANNING MICROSCOPY OF APOPTOSIS IN WHOLE MOUSE OVARIES  

EPA Science Inventory

Confocal Laser Scanning Microscopy of Apoptosis in Whole Mouse Ovaries. Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle...

421

PRECLINICAL STUDIES Cluvenone induces apoptosis via a direct target  

E-print Network

PRECLINICAL STUDIES Cluvenone induces apoptosis via a direct target in mitochondria: a possible Drive, La Jolla, San Diego, CA 92093, USA e-mail: abatova@ucsd.edu A. L. Yu The Genomics Research Center

Theodorakis, Emmanuel

422

Early induction of calpains in rotenone-mediated neuronal apoptosis  

Microsoft Academic Search

Rotenone is an inhibitor of mitochondrial complex I that produces a model of Parkinson's disease (PD), where neurons undergo apoptosis by caspase-dependent and\\/or caspase-independent pathways. Inhibition of calpains has recently been shown to attenuate neuronal apoptosis. This study aims to establish for the first time, the time-point of calpain activation with respect to the caspase activation and the possibility of

Minghui Jessica Chen; Yann Wan Yap; Meng Shyan Choy; Chor Hui Vivien Koh; Sze Jee Seet; Wei Duan; Matthew Whiteman; Nam Sang Cheung

2006-01-01

423

Drug-induced reactivation of apoptosis abrogates HIV-1 infection.  

PubMed

HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients. PMID:24086341

Hanauske-Abel, Hartmut M; Saxena, Deepti; Palumbo, Paul E; Hanauske, Axel-Rainer; Luchessi, Augusto D; Cambiaghi, Tavane D; Hoque, Mainul; Spino, Michael; D'Alliessi Gandolfi, Darlene; Heller, Debra S; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M; Tricta, Fernando; Connelly, John; Popowicz, Anthony M; Cone, Richard A; Holland, Bart; Pe'ery, Tsafi; Mathews, Michael B

2013-01-01

424

Accelerated Apoptosis Contributes to Aging-Related Hyperinflammation in Endotoxemia  

PubMed Central

Sepsis is associated with an increase in circulating levels of bacterial endotoxin. Sepsis is a particularly serious problem in the geriatric population due to the high mortality associated with it. However, it remains unknown whether this phenomenon is related to an increase of apoptosis in splenic cells. To study this, male Fischer-344 rats (young: 3-months old; aged: 24-months old) were subjected to endotoxemia by injection of LPS. Splenic samples were collected 4 h thereafter. Apoptosis was determined by cleaved caspase-3 levels and TUNEL staining. The levels of 3 pro-inflammatory mediators, TNF-?, IL-6 and high mobility group box -1 (HMGB-1), were also measured. Our results showed that while splenic cell apoptosis increased in both young and aged rats with endotoxemia, aged animals had much higher levels of apoptotic cell death. The elevated expression of cell cycle inhibitory protein P21 was also observed in aged animals after treatment with LPS. Moreover, endotoxemia significantly increased TNF-?, IL-6 and HMGB-1. The accelerated apoptosis in aged animals was correlated with significantly higher levels of TNF-?, IL-6 and HMGB-1. It is possible that this accelerated rate of apoptosis contributes to age-related hyperinflammation in endotoxemia. To investigate the factors involving accelerated apoptosis in aged animals, we analyzed the Fas/Fas ligand (Fas-L) pathway. Our results showed that Fas and Fas-L gene expression were markedly higher in the spleen in aged animals after LPS. Similarly, cleaved caspase-8 expression, a downstream element of Fas and Fas-L, was also significantly higher in aged rats after LPS. Fas-L neutralizing antibodies markedly decreased apoptosis and proinflammatory cytokines in aged animals after endotoxemia. Thus, there is substantial evidence that the Fas/Fas-L pathway may play an important role in LPS-induced accelerated apoptosis in aged animals. PMID:20428798

Zhou, Mian; Wu, Rongqian; Dong, Weifeng; Leong, Jennifer; Wang, Ping

2010-01-01

425

Increased apoptosis of germ cells in patients with AZFc deletions  

Microsoft Academic Search

Purpose  AZFc deletions are associated with variable testicular histology ranging from the Sertoli cell only to spermatogenic arrest\\u000a and hypospermatogenesis. Such variable phenotypes may be explained by progressive germ cell regression over time. Increased\\u000a apoptosis is likely responsible for progressive regression of spermatogenic potential. This study evaluated germ cell apoptosis\\u000a as a cause of the progressive decrease in the number of

Kyoko Yamada; Kazuyuki Fujita; Jinhua Quan; Masayuki Sekine; Katsunori Kashima; Tetsuro Yahata; Kenichi Tanaka

2010-01-01

426

BH3-only proteins in apoptosis and beyond: an overview  

Microsoft Academic Search

BH3-only BCL-2 family proteins are effectors of canonical mitochondrial apoptosis. They discharge their pro-apoptotic functions through BH1–3 pro-apoptotic proteins such as BAX and BAK, while their activity is suppressed by BH1–4 anti-apoptotic BCL-2 family members. The precise mechanism by which BH3-only proteins mediate apoptosis remains unresolved. The existing data are consistent with three mutually non-exclusive models (1) displacement of BH1–3

E Lomonosova; G Chinnadurai

2008-01-01

427

On the role of galectin-3 in cancer apoptosis  

Microsoft Academic Search

Galectin-3, a member of the ß-galactoside-binding gene family, is a multifunctional protein implicated in a variety of biological functions, including tumor cell adhesion, proliferation, differentiation, angiogenesis, cancer progression and metastasis. Recent studies revealed that intracellular galectin-3 exhibits the activity to suppress drug induced apoptosis and anoikis (apoptosis induced by the loss of cell anchorage) that contribute to cell survival. Resistance

S. Nakahara; N. Oka; A. Raz

2005-01-01

428