Molecular evidence for a recent demographic expansion in the puma (Puma concolor (Mammalia, Felidae

Directory of Open Access Journals (Sweden)

Eunice M. Matte

2013-01-01

Full Text Available The puma is an iconic predator that ranges throughout the Americas, occupying diverse habitats. Previous phylogeographic analyses have revealed that it exhibits moderate levels of genetic structure across its range, with few of the classically recognized subspecies being supported as distinct demographic units. Moreover, most of the species' molecular diversity was found to be in South America. To further investigate the phylogeographic structure and demographic history of pumas we analyzed mtDNA sequences from 186 individuals sampled throughout their range, with emphasis on South America. Our objectives were to refine the phylogeographic assessment within South America and to investigate the demographic history of pumas using a coalescent approach. Our results extend previous phylogeographic findings, reassessing the delimitation of historical population units in South America and demonstrating that this species experienced a considerable demographic expansion in the Holocene, ca. 8,000 years ago. Our analyses indicate that this expansion occurred in South America, prior to the hypothesized re-colonization of North America, which was therefore inferred to be even more recent. The estimated demographic history supports the interpretation that pumas suffered a severe demographic decline in the Late Pleistocene throughout their distribution, followed by population expansion and re-colonization of the range, initiating from South America.

The apoptotic response in HCT116BAX-/- cancer cells becomes rapidly saturated with increasing expression of a GFP-BAX fusion protein

Directory of Open Access Journals (Sweden)

Semaan Sheila J

2010-10-01

Full Text Available Abstract Background Many chemotherapeutic agents promote tumor cell death by activating the intrinsic pathway of apoptosis. Intrinsic apoptosis involves permeabilization of the mitochondrial outer membrane and the release of cytochrome c, a process that is controlled by proteins of the BCL2 gene family. Chemoresistance is often associated with abnormalities in concentrations of BCL2 family proteins. Although stoichiometirc interactions between anti-apoptotic and BH3-only BCL2 family proteins have been well documented as affecting cell death, the association between changes in BAX concentration and intrinsic apoptosis are poorly understood. Methods Exogenous GFP-murine Bax fusion constructs were transfected into BAX-deficient HCT116 cells. To titrate the expression of the fusion protein, GFP-BAX was cloned into a tetracycline sensitive expression cassette and cotransfected with a plasmid expressing the rtTA transcription factor into HCT116BAX-/- cells. Linear expression of the fusion gene was induced with doxycycline and monitored by quantitative PCR and immunoblotting. Cell death was assayed by DAPI staining cells after exposure to indomethacin, and scoring nuclei for condensed chromatin and fragmented nuclei. Results HCT116BAX-/- cells were resistant to indomethacin, but susceptibility could be recovered in cells expressing a GFP-BAX fusion protein. Titration of GFP-BAX expression revealed that the concentration of BAX required to induce a saturating apoptosis response from baseline, was rapidly achieved. Increased levels of GFP-BAX were unable to stimulate higher levels of cell death. Examination of GFP-BAX distribution before and after indomethacin treatment indicated that BAX protein did not form aggregates when present at sub-lethal concentrations. Conclusion Within the limitations of this experimental system, BAX-dependent apoptosis in HCT116 cells exhibits an all-or-none response depending on the level of BAX protein present. The lack of

Livestock Predation by Puma (Puma concolor) in the Highlands of a Southeastern Brazilian Atlantic Forest.

Science.gov (United States)

Palmeira, Francesca Belem Lopes; Trinca, Cristiano Trapé; Haddad, Claudio Maluf

2015-10-01

We evaluated local opinion about reducing livestock losses to puma (Puma concolor) and the potential for conflict among livestock breeders inside a protected area in the highlands of a southeastern Brazilian Atlantic forest. We also quantified the number and type of livestock losses, and determined if predation by puma was correlated with property profile and landscape characteristics. We conducted semistructured interviews with 42 livestock breeders sampled in 36 rural properties. When asked how to reduce predation, 33% of livestock breeders refused to answer, 26% suggested improving livestock husbandry practices, 19% stated that there was no appropriate action, 17% favored removing the "problem" individual, and 5 % suggested killing the puma. Opinion on how to solve predation was independent of herd size and history of losses, and was correlated with respondent age class. Older respondents tended to suggest removing or killing pumas. Attitudes toward predation represented high potential for conflict among livestock breeders who demonstrated high discordance among responses. Horses were the most common prey (51%), followed by cattle (28%), sheep (17%), and goats (4%); totaling 47 animals attacked between 2004 and 2007. Annual predation was approximately 12 ± 5 animals, equivalent to 0.4% of the total livestock. Property elevation and distance from the urban center were the main predictors of predation probability. This survey used a novel approach that has not been addressed directly in other studies on livestock predation and demonstrated that the high potential for conflict among livestock breeders should be considered before implementing management actions.

Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737.

Science.gov (United States)

Renault, Thibaud T; Teijido, Oscar; Missire, Florent; Ganesan, Yogesh Tengarai; Velours, Gisèle; Arokium, Hubert; Beaumatin, Florian; Llanos, Raul; Athané, Axel; Camougrand, Nadine; Priault, Muriel; Antonsson, Bruno; Dejean, Laurent M; Manon, Stéphen

2015-07-01

Bax cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis. Bcl-xL is an important regulator of this event and was recently shown to promote the retrotranslocation of mitochondrial Bax to the cytosol. The present study identifies a new aspect of the regulation of Bax localization by Bcl-xL: in addition to its role in Bax inhibition and retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL expression levels led to an increase of Bax mitochondrial content. This finding was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by retrotranslocation, as we observed that Bcl-xLΔC, which is unable to promote Bax retrotranslocation, was more efficient than the full-length protein in stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT-737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes mitochondria to permeabilization and cytochrome c release. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nuisance ecology: do scavenging condors exact foraging costs on pumas in Patagonia?

Science.gov (United States)

Elbroch, L Mark; Wittmer, Heiko U

2013-01-01

Predation risk describes the energetic cost an animal suffers when making a trade off between maximizing energy intake and minimizing threats to its survival. We tested whether Andean condors (Vultur gryphus) influenced the foraging behaviors of a top predator in Patagonia, the puma (Puma concolor), in ways comparable to direct risks of predation for prey to address three questions: 1) Do condors exact a foraging cost on pumas?; 2) If so, do pumas exhibit behaviors indicative of these risks?; and 3) Do pumas display predictable behaviors associated with prey species foraging in risky environments? Using GPS location data, we located 433 kill sites of 9 pumas and quantified their kill rates. Based upon time pumas spent at a carcass, we quantified handling time. Pumas abandoned >10% of edible meat at 133 of 266 large carcasses after a single night, and did so most often in open grasslands where their carcasses were easily detected by condors. Our data suggested that condors exacted foraging costs on pumas by significantly decreasing puma handling times at carcasses, and that pumas increased their kill rates by 50% relative to those reported for North America to compensate for these losses. Finally, we determined that the relative risks of detection and associated harassment by condors, rather than prey densities, explained puma "giving up times" (GUTs) across structurally variable risk classes in the study area, and that, like many prey species, pumas disproportionately hunted in high-risk, high-resource reward areas.

A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection.

Science.gov (United States)

Niu, Xin; Brahmbhatt, Hetal; Mergenthaler, Philipp; Zhang, Zhi; Sang, Jing; Daude, Michael; Ehlert, Fabian G R; Diederich, Wibke E; Wong, Eve; Zhu, Weijia; Pogmore, Justin; Nandy, Jyoti P; Satyanarayana, Maragani; Jimmidi, Ravi K; Arya, Prabhat; Leber, Brian; Lin, Jialing; Culmsee, Carsten; Yi, Jing; Andrews, David W

2017-04-20

Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM. Small-molecule inhibition of Bax/Bak oligomerization allowed cells to evade apoptotic stimuli and rescued neurons from death after excitotoxicity, demonstrating that oligomerization of Bax is essential for MOMP. Our discovery of small-molecule Bax/Bak inhibitors provides novel tools for the investigation of the mechanisms leading to MOMP and will ultimately facilitate development of compounds inhibiting Bax/Bak in acute and chronic degenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

PUMAS: Practical Uses of Math And Science

Science.gov (United States)

Kahn, R. A.

2009-12-01

For more than ten years, PUMAS has provided a forum for disseminating peer-reviewed examples of Practical Uses of Math And Science, aimed at helping pre-college teachers enrich their presentation of math and science topics. Contributors include scientists, engineers, and content experts from many disciplines. The innovative ideas in PUMAS examples tend to be treasures, containing the ‘sparks’ of understanding that comes only from having real-life experience with the material. Examples can be essays, anecdotes, problems, demonstrations, or activities, and can be written in any style that serves the material well. They are keyed to the National Standards and Benchmarks, which provide the critical connection to K-12 curriculum guidelines, and the peer-review process involves at least one scientist with a relevant background, and at least one teacher at an appropriate grade level. The PUMAS Web Site has recently been upgraded. It is now a NASA-wide facility, recognized by both the National Science Teachers Association (NSTA) and the National Council of Teachers of Mathematics (NCTM). This presentation will describe and illustrate the operation of PUMAS, will highlight a few of our many treasures, and will appeal to scientists interested in contributing meaningfully to pre-college education to consider submitting examples to PUMAS.

PuMA: the Porous Microstructure Analysis software

Science.gov (United States)

Ferguson, Joseph C.; Panerai, Francesco; Borner, Arnaud; Mansour, Nagi N.

2018-01-01

The Porous Microstructure Analysis (PuMA) software has been developed in order to compute effective material properties and perform material response simulations on digitized microstructures of porous media. PuMA is able to import digital three-dimensional images obtained from X-ray microtomography or to generate artificial microstructures. PuMA also provides a module for interactive 3D visualizations. Version 2.1 includes modules to compute porosity, volume fractions, and surface area. Two finite difference Laplace solvers have been implemented to compute the continuum tortuosity factor, effective thermal conductivity, and effective electrical conductivity. A random method has been developed to compute tortuosity factors from the continuum to rarefied regimes. Representative elementary volume analysis can be performed on each property. The software also includes a time-dependent, particle-based model for the oxidation of fibrous materials. PuMA was developed for Linux operating systems and is available as a NASA software under a US & Foreign release.

Ppr - Puma: a successful acquisition?

OpenAIRE

M. Buongiorno; B. Rovetta

2010-01-01

The PPR-Puma case explores the issue of evaluating the acquisition of Puma by the PPR group. Starting from the assessment of the business strategy and the analysis of the competitive scenario and firm-specific positioning, the case moves to a sound financial analysis and company valuation to be carried out with the objective to assess the actual value of the target company and the potential synergies to be achieved by the bidder. PPR is a very well-known player in the retail and luxury busine...

PUMA: An Operating System for Massively Parallel Systems

Directory of Open Access Journals (Sweden)

Stephen R. Wheat

1994-01-01

Full Text Available This article presents an overview of PUMA (Performance-oriented, User-managed Messaging Architecture, a message-passing kernel for massively parallel systems. Message passing in PUMA is based on portals – an opening in the address space of an application process. Once an application process has established a portal, other processes can write values into the portal using a simple send operation. Because messages are written directly into the address space of the receiving process, there is no need to buffer messages in the PUMA kernel and later copy them into the applications address space. PUMA consists of two components: the quintessential kernel (Q-Kernel and the process control thread (PCT. Although the PCT provides management decisions, the Q-Kernel controls access and implements the policies specified by the PCT.

Models of regional habitat quality and connectivity for pumas (Puma concolor) in the southwestern United States.

Science.gov (United States)

Dickson, Brett G; Roemer, Gary W; McRae, Brad H; Rundall, Jill M

2013-01-01

The impact of landscape changes on the quality and connectivity of habitats for multiple wildlife species is of global conservation concern. In the southwestern United States, pumas (Puma concolor) are a well distributed and wide-ranging large carnivore that are sensitive to loss of habitat and to the disruption of pathways that connect their populations. We used an expert-based approach to define and derive variables hypothesized to influence the quality, location, and permeability of habitat for pumas within an area encompassing the entire states of Arizona and New Mexico. Survey results indicated that the presence of woodland and forest cover types, rugged terrain, and canyon bottom and ridgeline topography were expected to be important predictors of both high quality habitat and heightened permeability. As road density, distance to water, or human population density increased, the quality and permeability of habitats were predicted to decline. Using these results, we identified 67 high quality patches across the study area, and applied concepts from electronic circuit theory to estimate regional patterns of connectivity among these patches. Maps of current flow among individual pairs of patches highlighted possible pinch points along two major interstate highways. Current flow summed across all pairs of patches highlighted areas important for keeping the entire network connected, regardless of patch size. Cumulative current flow was highest in Arizona north of the Colorado River and around Grand Canyon National Park, and in the Sky Islands region owing to the many small habitat patches present. Our outputs present a first approximation of habitat quality and connectivity for dispersing pumas in the southwestern United States. Map results can be used to help target finer-scaled analyses in support of planning efforts concerned with the maintenance of puma metapopulation structure, as well as the protection of landscape features that facilitate the dispersal

Models of regional habitat quality and connectivity for pumas (Puma concolor in the southwestern United States.

Directory of Open Access Journals (Sweden)

Brett G Dickson

Full Text Available The impact of landscape changes on the quality and connectivity of habitats for multiple wildlife species is of global conservation concern. In the southwestern United States, pumas (Puma concolor are a well distributed and wide-ranging large carnivore that are sensitive to loss of habitat and to the disruption of pathways that connect their populations. We used an expert-based approach to define and derive variables hypothesized to influence the quality, location, and permeability of habitat for pumas within an area encompassing the entire states of Arizona and New Mexico. Survey results indicated that the presence of woodland and forest cover types, rugged terrain, and canyon bottom and ridgeline topography were expected to be important predictors of both high quality habitat and heightened permeability. As road density, distance to water, or human population density increased, the quality and permeability of habitats were predicted to decline. Using these results, we identified 67 high quality patches across the study area, and applied concepts from electronic circuit theory to estimate regional patterns of connectivity among these patches. Maps of current flow among individual pairs of patches highlighted possible pinch points along two major interstate highways. Current flow summed across all pairs of patches highlighted areas important for keeping the entire network connected, regardless of patch size. Cumulative current flow was highest in Arizona north of the Colorado River and around Grand Canyon National Park, and in the Sky Islands region owing to the many small habitat patches present. Our outputs present a first approximation of habitat quality and connectivity for dispersing pumas in the southwestern United States. Map results can be used to help target finer-scaled analyses in support of planning efforts concerned with the maintenance of puma metapopulation structure, as well as the protection of landscape features that facilitate

Involvement of PUMA in pericyte migration induced by methamphetamine.

Science.gov (United States)

Zhang, Yanhong; Zhang, Yuan; Bai, Ying; Chao, Jie; Hu, Gang; Chen, Xufeng; Yao, Honghong

2017-07-01

Mounting evidence indicates that methamphetamine causes blood-brain barrier damage, with emphasis on endothelial cells. The role of pericytes in methamphetamine-induced BBB damage remains unknown. Our study demonstrated that methamphetamine increased the migration of pericytes from the endothelial basement membrane. However, the detailed mechanisms underlying this process remain poorly understood. Thus, we examined the molecular mechanisms involved in methamphetamine-induced pericyte migration. The results showed that exposure of C3H/10T1/2 cells and HBVPs to methamphetamine increased PUMA expression via activation of the sigma-1 receptor, MAPK and Akt/PI3K pathways. Moreover, methamphetamine treatment resulted in the increased migration of C3H/10T1/2 cells and HBVPs. Knockdown of PUMA in pericytes transduced with PUMA siRNA attenuated the methamphetamine-induced increase in cell migration through attenuation of integrin and tyrosine kinase mechanisms, implicating a role of PUMA in the migration of C3H/10T1/2 cells and HBVPs. This study has demonstrated that methamphetamine-mediated pericytes migration involves PUMA up-regulation. Thus, targeted studies of PUMA could provide insights to facilitate the development of a potential therapeutic approach for alleviation of methamphetamine-induced pericyte migration. Copyright © 2017. Published by Elsevier Inc.

Table scraps: inter-trophic food provisioning by pumas.

Science.gov (United States)

Elbroch, L Mark; Wittmer, Heiko U

2012-10-23

Large carnivores perform keystone ecological functions through direct predation, or indirectly, through food subsidies to scavengers or trophic cascades driven by their influence on the distributions of their prey. Pumas (Puma concolor) are an elusive, cryptic species difficult to study and little is known about their inter-trophic-level interactions in natural communities. Using new GPS technology, we discovered that pumas in Patagonia provided 232 ± 31 kg of edible meat/month/100 km(2) to near-threatened Andean condors (Vultur gryphus) and other members of a diverse scavenger community. This is up to 3.1 times the contributions by wolves (Canis lupus) to communities in Yellowstone National Park, USA, and highlights the keystone role large, solitary felids play in natural systems. These findings are more pertinent than ever, for managers increasingly advocate controlling pumas and other large felids to bolster prey populations and mitigate concerns over human and livestock safety, without a full understanding of the potential ecological consequences of their actions.

Harwell hardens Staeubli Puma

International Nuclear Information System (INIS)

Watson, C.J.H.

1992-01-01

The Remote Handling and Robotics Department at Harwell, has argued that it ought to be possible to combine all the advantages of the industrial robot - its off-the-shelf availability, low cost and high reliability - with the specific requirements of the nuclear industry, by subjecting an industrial robot to a programme of ''nuclear engineering''. After a careful evaluation, they selected the Staubli Unimation Puma 760 robot as the first candidate for this programme. Three years, and several Pound 100,000s later, they have launched on the market the world's first Nuclear Engineered Advanced Telerobot, or NEATER, as it is called. The device is manufactured by Staubli Unimation, to the same mechanical and QA standards as a standard PUMA, but with all the non-metallic components replaced by radiation tolerant materials. These were chosen by Harwell, after extensive radiation testing and design work, to ensure that the whole robot can tolerate up to 100 MRads - i.e. the highest radiation dose that a robot is likely to experience in a normal nuclear facility. It is controlled, like a normal PUMA, by a VAL 2 industrial robot controller, but this is ''front-ended'' by the Harwell Telerobotic Controller, a PC-based controller, which takes human commands from mechanical ''Input Device'' and translates these into VAL commands, which can then be interpreted by the VAL 2 controller in the normal way. (Author)

The PUMA test program and data analysis

International Nuclear Information System (INIS)

Han, J.T.; Morrison, D.L.

1997-01-01

The PUMA test program is sponsored by the U.S. Nuclear Regulatory Commission to provide data that are relevant to various Boiling Water Reactor phenomena. The author briefly describes the PUMA test program and facility, presents the objective of the program, provides data analysis for a large-break loss-of-coolant accident test, and compares the data with a RELAP5/MOD 3.1.2 calculation

Diet of pumas (Puma concolor) in Sonora, Mexico, as determined by GPS kill sites and molecular identified scat, with comments on jaguar (Panthera onca) diet

Science.gov (United States)

Cassaigne, Ivonne; Medellin, Rodrigo A.; Thompson, Ron W.; Culver, Melanie; Ochoa, Alexander; Vargas, Karla; Childs, Jack L.; Sanderson, Jim; List, Rurik; Torres-Gomez, Armando

2016-01-01

We documented puma (Puma concolor) and jaguar (Panthera onca) prey consumption in northeastern Sonora, Mexico, by investigating global positioning system cluster sites (n = 220), and conducting molecular analyses of scat (n = 116) collected between 2011 and 2013. We used camera trap data (n = 8,976 camera days) to estimate relative abundances of pumas and jaguars. Deer (Odocoileus virginianus) was the most frequent prey for puma found at kill sites (67%) and identified from scat (74%), although based on relative numbers of prey consumed, deer represented 45% and lagomorphs 20% of the proportion of all individuals eaten. A variety of small prey (weighing Sonora.

Therapeutic Response to Non-genotoxic Activation of p53 by Nutlin3a Is Driven by PUMA-Mediated Apoptosis in Lymphoma Cells

Directory of Open Access Journals (Sweden)

Liz J. Valente

2016-03-01

Full Text Available Nutlin3a is a small-molecule antagonist of MDM2 that promotes non-genotoxic activation of p53 through p53 protein stabilization and transactivation of p53 target genes. Nutlin3a is the forerunner of a class of cancer therapeutics that have reached clinical trials. Using transgenic and gene-targeted mouse models lacking the critical p53 target genes, p21, Puma, and Noxa, we found that only loss of PUMA conferred profound protection against Nutlin3a-induced killing in both non-transformed lymphoid cells and Eμ-Myc lymphomas in vitro and in vivo. CRISPR/Cas9-mediated targeting of the PUMA gene rendered human hematopoietic cancer cell lines markedly resistant to Nutlin3a-induced cell death. These results demonstrate that PUMA-mediated apoptosis, but not p21-mediated cell-cycle arrest or senescence, is a critical determinant of the therapeutic response to non-genotoxic p53 activation by Nutlin3a. Importantly, in human cancer, PUMA expression may predict patient responses to treatment with MDM2 antagonists.

Inhibition of p38 MAPK enhances ABT-737-induced cell death in melanoma cell lines: novel regulation of PUMA.

Science.gov (United States)

Keuling, Angela M; Andrew, Susan E; Tron, Victor A

2010-06-01

The mitogen-activated protein kinase (MAPK) pathway is constitutively activated in the majority of melanomas, promoting cell survival, proliferation and migration. In addition, anti-apoptotic Bcl-2 family proteins Mcl-1, Bcl-xL and Bcl-2 are frequently overexpressed, contributing to melanoma's well-documented chemoresistance. Recently, it was reported that the combination of MAPK pathway inhibition by specific MEK inhibitors and Bcl-2 family inhibition by BH3-mimetic ABT-737 synergistically induces apoptotic cell death in melanoma cell lines. Here we provide the first evidence that inhibition of another key MAPK, p38, synergistically induces apoptosis in melanoma cells in combination with ABT-737. We also provide novel mechanistic data demonstrating that inhibition of p38 increases expression of pro-apoptotic Bcl-2 protein PUMA. Furthermore, we demonstrate that PUMA can be cleaved by a caspase-dependent mechanism during apoptosis and identify what appears to be the PUMA cleavage product. Thus, our findings suggest that the combination of ABT-737 and inhibition of p38 is a promising, new treatment strategy that acts through a novel PUMA-dependent mechanism.

Biosynthesized Silver Nanoparticles Used in Preservative Solutions for Chrysanthemum cv. Puma

Directory of Open Access Journals (Sweden)

Luis M. Carrillo-López

2016-01-01

Full Text Available The use of pulse solutions containing antimicrobials has been reported, but more research is necessary. To increase vase life and to study their effect on opening inflorescences, silver nanoparticles were used in vase solutions for cv. Puma Chrysanthemum stems. The nanoparticles were synthesized biologically using Chenopodium ambrosioides L. applied at concentrations of 0.01, 0.05, 0.1, 0.5, 1, and 5 mM and compared with a control. Treatments were replicated five times. The stems were cut to 50 cm and observed until the end of their vase life. Low concentrations of silver nanoparticles promoted inflorescence opening and leaf yellowing, while the control leaves remained green, but there was a lower degree of inflorescence opening. High concentrations of silver nanoparticles (0.5, 1, and 5 mM caused senescence due to low water uptake through the stems. Statistical differences in inflorescence opening and diameter, bacterial growth (CFU mL−1 in vase solutions, fresh weight, water uptake, and vase life were found among treatments. Longer vase life and less weight loss were observed in the stems exposed to low concentrations of silver nanoparticles. Low concentrations of silver nanoparticles promoted inflorescence opening and increased vase life of Chrysanthemum cv. Puma.

Jaguar interactions with pumas and prey at the northern edge of jaguars’ range

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Carmina E. Gutiérrez-González

2017-01-01

Full Text Available We present the first study that evaluates jaguar-puma interactions in the arid lands of northern Mexico, where jaguars have their northernmost breeding population and both predators are persecuted for livestock depredation. We tested whether jaguars are the dominant species in this unique ecosystem, where: (1 pumas outnumber jaguars, (2 pumas are better adapted to arid environments, and (3 jaguars and pumas are of similar size. We analyzed four years of data with two approaches; a two species conditional occupancy model and an activity patterns analysis. We used camera location and prey presence as covariates for jaguar and puma detection and presence probabilities. We also explored overlap in activities of predators and prey. Where both species were detected, peccary presence was positively correlated with both jaguar and puma presence, whereas in areas where jaguars were detected but pumas were not, deer presence explained the probability of jaguar presence. We found that both predators were more likely to co-occur together than to be found independently, and so we rejected the hypothesis that jaguars were the dominant species in our study area. Predators were mainly nocturnal and their activity patterns overlapped by 60%. Jaguar, as compared with puma, overlapped more with deer and calves; puma overlapped with calves more than with other prey, suggesting a preference. We believe exploring predator relationships at different scales may help elucidate mechanisms that regulate their coexistence.

Budování sportovní značky PUMA

OpenAIRE

Lečková, Veronika

2015-01-01

Title: PUMA branding Objective: The aim of diploma thesis is to get improvement proposal which could be used for further building of PUMA brand. The research will be carried out on two samples of respondents. The first sample will be Generation Y which is defined by Bergh (2012). A second sample of respondents are employees of the company PUMA. Methods: The entire thesis is focused and based on standardized method of the brand personality from J. L. Aaker (1997), adapted by the authors Geuens...

Anti-cancer effect of novel PAK1 inhibitor via induction of PUMA-mediated cell death and p21-mediated cell cycle arrest.

Science.gov (United States)

Woo, Tae-Gyun; Yoon, Min-Ho; Hong, Shin-Deok; Choi, Jiyun; Ha, Nam-Chul; Sun, Hokeun; Park, Bum-Joon

2017-04-04

Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner. Indeed, in PUMA-deficient cells, this chemical did not show anti-proliferating effect. This chemical possessed very strong PAK1 inhibition activity that it suppressed BAD (Bcl-2-asoociated death promoter) phosphorylation and meta-phase arrest via Aurora kinase inactivation in lower concentration than that of previous PAK1 kinase, FRAX486 and AG879. Moreover, our chemical obviously induced p21/WAF1/CIP1 (Cyclin-dependent kinase inhibitor 1A) expression by releasing from Bcl-2 (B-cell lymphoma-2) and by inhibition of AKT-mediated p21 suppression. Considering our result, IPP-14 and its derivatives would be possible candidates for PAK1 and p21 induction targeted anti-cancer drug.

Melatonin promotes Bax sequestration to mitochondria reducing cell susceptibility to apoptosis via the lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid

KAUST Repository

Radogna, Flavia

2015-03-01

Extra-neurological functions of melatonin include control of the immune system and modulation of apoptosis. We previously showed that melatonin inhibits the intrinsic apoptotic pathway in leukocytes via stimulation of high affinity MT1/MT2 receptors, thereby promoting re-localization of the anti-apoptotic Bcl-2 protein to mitochondria. Here we show that Bcl-2 sequesters pro-apoptotic Bax into mitochondria in an inactive form after melatonin treatment, thus reducing cell propensity to apoptosis. Bax translocation and the anti-apoptotic effect of melatonin are strictly dependent on the presence of Bcl-2, and on the 5-lipoxygenase (5-LOX) metabolite 5-hydroxyeicosatetraenoic acid (5-HETE), which we have previously shown to be produced as a consequence of melatonin binding to its low affinity target calmodulin. Therefore, the anti-apoptotic effect of melatonin requires the simultaneous, independent interaction with high (MT1/MT2) and low (calmodulin) affinity targets, eliciting two independent signal transduction pathways converging into Bax sequestration and inactivation. MT1/MT2 vs. lipoxygenase pathways are activated by 10-9 vs. 10-5M melatonin, respectively; the anti-apoptotic effect of melatonin is achieved at 10-5M, but drops to 10-9M upon addition of exogenous 5-HETE, revealing that lipoxygenase activation is the rate-limiting pathway. Therefore, in areas of inflammation with increased 5-HETE levels, physiological nanomolar concentrations of melatonin may suffice to maintain leukocyte viability.

Variability in assays used for detection of lentiviral infection in bobcats (Lynx rufus), pumas (Puma concolor), and ocelots (Leopardus pardalis)

Science.gov (United States)

Franklin, S.P.; Troyer, J.L.; TerWee, J.A.; Lyren, L.M.; Kays, R.W.; Riley, S.P.D.; Boyce, W.M.; Crooks, K.R.; VandeWoude, S.

2007-01-01

Although lentiviruses similar to feline immunodeficiency virus (FIV) are known to infect numerous felid species, the relative utility of assays used for detecting lentiviral infection has not been compared for many of these hosts. We tested bobcats (Lynx rufus), pumas (Felis concolor), and ocelots (Leopardus pardalis) for exposure to lentivirus using five different assays: puma lentivirus (PLV), African lion lentivirus (LLV), and domestic cat FIV-based immunoblots, a commercially available enzyme-linked immunosorbent assay (ELISA) kit, and nested polymerase chain reaction (PCR). Puma lentivirus immunoblots identified more seropositive individuals than the other antibody-detection assays. The commercial ELISA provided a fair ability to recognize seropositive samples when compared with PLV immunoblot for screening bobcats and ocelots, but not pumas. Polymerase chain reaction identified fewer positive samples than PLV immunoblot for all three species. Immunoblot results were equivalent whether the sample tested was serum, plasma, or whole blood. The results from this study and previous investigations suggest that the PLV immunoblot has the greatest ability to detect reactive samples when screening wild felids of North America and is unlikely to produce false positive results. However, the commercial ELISA kit may provide ap adequate alternative for screening of some species and is more easily adapted to field conditions. ?? Wildlife Disease Association 2007.

Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

Shukla, Shatrunajay [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Sharma, Ankita [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Pandey, Vivek Kumar [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India); Raisuddin, Sheikh [Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Kakkar, Poonam, E-mail: kakkarp59@gmail.com [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India)

2016-01-15

Post-translational modifications i.e. phosphorylation and acetylation are pivotal requirements for proper functioning of eukaryotic proteins. The current study aimed to decode the impact of acetylation/deacetylation of non-histone targets i.e. FoxO1/3a and p53 of sirtuins (NAD{sup +} dependent enzymes with lysine deacetylase activity) in berberine treated human hepatoma cells. Berberine (100 μM) inhibited sirtuins significantly (P < 0.05) at transcriptional level as well as at translational level. Combination of nicotinamide (sirtuin inhibitor) with berberine potentiated sirtuins inhibition and increased the expression of FoxO1/3a and phosphorylation of p53 tumor suppressor protein. As sirtuins deacetylate non-histone targets including FoxO1/3a and p53, berberine increased the acetylation load of FoxO1/3a and p53 proteins. Acetylated FoxO and p53 proteins transcriptionally activate BH3-only proteins Bim and PUMA (3.89 and 3.87 fold respectively, P<0.001), which are known as direct activator of pro-apoptotic Bcl-2 family protein Bax that culminated into mitochondria mediated activation of apoptotic cascade. Bim/PUMA knock-down showed no changes in sirtuins' expression while cytotoxicity induced by berberine and nicotinamide was curtailed up to 28.3% (P < 0.001) and it restored pro/anti apoptotic protein ratio in HepG2 cells. Sirtuins inhibition was accompanied by decline in NAD{sup +}/NADH ratio, ATP generation, enhanced ROS production and decreased mitochondrial membrane potential. TEM analysis confirmed mitochondrial deterioration and cell damage. SRT-1720 (1–10 μM), a SIRT-1 activator, when pre-treated with berberine (25 μM), reversed sirtuins expression comparable to control and significantly restored the cell viability (P < 0.05). Thus, our findings suggest that berberine mediated sirtuins inhibition resulting into FoxO1/3a and p53 acetylation followed by BH3-only protein Bim/PUMA activation may in part be responsible for mitochondria

PUMA Version 6 Multiplatform with Facilities to be coupled with other Simulation Models

International Nuclear Information System (INIS)

Grant, Carlos

2013-01-01

PUMA is a code for nuclear reactor calculation used in all nuclear installations in Argentina for simulation of fuel management, power cycles and transient events by means of spatial kinetic diffusion theory in 3D. For the versions used up to now the WINDOWS platform was used with very good results. Nowadays PUMA must work in different operative systems, LINUX among others, and must also have facilities to be coupled with other models. For this reason this new version was reprogrammed in ADA, language oriented to a safe programming and be found in any operative system. In former versions PUMA was executed through macro instructions written in LOGO. For this version it is possible to use also PYTHON, which makes also possible the access in execution time to internal data of PUMA. The use of PYTHON allows a easy way to couple PUMA with other codes. The possibilities of this new version of PUMA are shown by means of examples of input data and process control using PYTHON and LOGO. It is discussed the implementation of this methodology in other codes to be coupled with PUMA for versions run in WINDOWS and LINUX. (author)

Explaining reported puma-related behaviors and behavioral intentions among northern Arizona residents

Science.gov (United States)

Mattson, David J.; Ruther, Elizabeth J.

2012-01-01

Management of pumas in the American West is typified by conflict among stakeholders plausibly rooted in life experiences and worldviews. We used a mail questionnaire to assess demographics, nature-views, puma-related life experiences and behaviors, and support for puma-related policies among residents of northern Arizona. Data from the questionnaire (n = 693 respondents) were used to model behaviors and support for policies. Compared to models based on nature-views and life experiences, those based on demographics had virtually no support from the data. The Utilitarian/Dominionistic nature-view had the strongest effect of any variable in six of seven models, and was associated with firearms and opposition to policies that would limit killing pumas. The Humanistic/Moralistic nature-view was positively associated with non-lethal behaviors and policies in five models. Gender had the strongest effect of any demographic variable. Compared to demographics alone, our results suggest that worldviews provide a more meaningful explanation of reported human behaviors and behavioral intentions regarding pumas.

Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis.

Science.gov (United States)

Renault, Thibaud T; Floros, Konstantinos V; Elkholi, Rana; Corrigan, Kelly-Ann; Kushnareva, Yulia; Wieder, Shira Y; Lindtner, Claudia; Serasinghe, Madhavika N; Asciolla, James J; Buettner, Christoph; Newmeyer, Donald D; Chipuk, Jerry E

2015-01-08

Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size. Complementary biochemical, cellular, in vivo, and ex vivo studies reveal that Mfn1, a GTPase involved in mitochondrial fusion, establishes a mitochondrial size that is permissive for proapoptotic BCL-2 family function. Cells with hyperfragmented mitochondria, along with size-restricted OMM model systems, fail to support BAX-dependent membrane association and permeabilization due to an inability to stabilize BAXα9·membrane interactions. This work identifies a mechanistic contribution of mitochondrial size in dictating BAX activation, MOMP, and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Hábitos alimentarios del Puma concolor (Carnivora: Felidae en el Parque Nacional Natural Puracé, Colombia

Directory of Open Access Journals (Sweden)

Andrés Hernández-Guzmán

2011-09-01

Full Text Available La dieta de Puma concolor es ampliamente conocida a lo largo de su distribución, sin embargo, en Colombia no se ha realizado ningún estudio sobre sus hábitos alimentarios. Entre 2007-2009, la dieta de puma fue analizada en el Parque-Nacional-Natural-Puracé, sur occidente de los Andes colombianos. Ítems alimenticios de cinco especies presa fueron identificadas en su dieta; el venado conejo (Pudu mephistophiles es la presa más importante. Como herramienta complementaria para la identificación de huesos y pelos contenidos en heces (n=60, se instalaron seis cámarastrampa en lugares estratégicos, para registrar la presencia de pumas y presas potenciales. El descubrimiento de la dependencia de los pumas con el pudú sugiere una única adaptación de los pumas de paramo a la disponibilidad de presas y resalta su importancia como reguladores de las poblaciones presa. Estos resultados contribuyen a incrementar el poco conocimiento sobre la ecología de pumas de los Andes, de sus presas y de las especies en su conjunto en Colombia. Obtener información sobre el grupo de presas de pumas en diferentes ecosistemas, es esencial para entender los requerimientos regionales para su supervivencia y diseñar acciones de conservación que permitan seguir/evaluar las necesidades particulares de áreas protegidas en toda su distribución.Food habits of Puma concolor (Carnivora: Felidae in the Parque Nacional Natural Puracé,Colombia. Neotropical puma (Puma concolor diet is scarcely known, in particular that of mountain dwelling individuals from Northern South America. This is the first study on pumas from the paramo and the first puma diet analysis for Colombia. The puma diet was studied from 2007 to 2009 in the Puracé National Park in the South Colombian Andes. Paramos are unique neotropical high altitude ecosystems which store and regulate water, and are currently threatened by agricultural expansion and climate change. Seven latrines were monitored for

Direct adaptive control of a PUMA 560 industrial robot

Science.gov (United States)

Seraji, Homayoun; Lee, Thomas; Delpech, Michel

1989-01-01

The implementation and experimental validation of a new direct adaptive control scheme on a PUMA 560 industrial robot is described. The testbed facility consists of a Unimation PUMA 560 six-jointed robot and controller, and a DEC MicroVAX II computer which hosts the Robot Control C Library software. The control algorithm is implemented on the MicroVAX which acts as a digital controller for the PUMA robot, and the Unimation controller is effectively bypassed and used merely as an I/O device to interface the MicroVAX to the joint motors. The control algorithm for each robot joint consists of an auxiliary signal generated by a constant-gain Proportional plus Integral plus Derivative (PID) controller, and an adaptive position-velocity (PD) feedback controller with adjustable gains. The adaptive independent joint controllers compensate for the inter-joint couplings and achieve accurate trajectory tracking without the need for the complex dynamic model and parameter values of the robot. Extensive experimental results on PUMA joint control are presented to confirm the feasibility of the proposed scheme, in spite of strong interactions between joint motions. Experimental results validate the capabilities of the proposed control scheme. The control scheme is extremely simple and computationally very fast for concurrent processing with high sampling rates.

Interfacing models of wildlife habitat and human development to predict the future distribution of puma habitat

Science.gov (United States)

Burdett, Christopher L.; Crooks, Kevin R.; Theobald, David M.; Wilson, Kenneth R.; Boydston, Erin E.; Lyren, Lisa A.; Fisher, Robert N.; Vickers, T. Winston; Morrison, Scott A.; Boyce, Walter M.

2010-01-01

The impact of human land uses on ecological systems typically differ relative to how extensively natural conditions are modified. Exurban development is intermediate-intensity residential development that often occurs in natural landscapes. Most species-habitat models do not evaluate the effects of such intermediate levels of human development and even fewer predict how future development patterns might affect the amount and configuration of habitat. We addressed these deficiencies by interfacing a habitat model with a spatially-explicit housing-density model to study the effect of human land uses on the habitat of pumas (Puma concolor) in southern California. We studied the response of pumas to natural and anthropogenic features within their home ranges and how mortality risk varied across a gradient of human development. We also used our housing-density model to estimate past and future housing densities and model the distribution of puma habitat in 1970, 2000, and 2030. The natural landscape for pumas in our study area consisted of riparian areas, oak woodlands, and open, conifer forests embedded in a chaparral matrix. Pumas rarely incorporated suburban or urban development into their home ranges, which is consistent with the hypothesis that the behavioral decisions of individuals can be collectively manifested as population-limiting factors at broader spatial scales. Pumas incorporated rural and exurban development into their home ranges, apparently perceiving these areas as modified, rather than non-habitat. Overall, pumas used exurban areas less than expected and showed a neutral response to rural areas. However, individual pumas that selected for or showed a neutral response to exurban areas had a higher risk of mortality than pumas that selected against exurban habitat. Exurban areas are likely hotspots for puma-human conflict in southern California. Approximately 10% of our study area will transform from exurban, rural, or undeveloped areas to suburban or

The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax

Czech Academy of Sciences Publication Activity Database

Lidman, M.; Pokorná, Šárka; Dingeldein, A. P. G.; Sparrman, T.; Wallgren, M.; Šachl, Radek; Hof, Martin; Gröbner, G.

2016-01-01

Roč. 1858, č. 6 (2016), s. 1288-1297 ISSN 0005-2736 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388955 Keywords : Apoptosis * Bax-protein * Calorimetry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2016

Counterpart experimental study of ISP-42 PANDA tests on PUMA facility

International Nuclear Information System (INIS)

Yang, Jun; Choi, Sung-Won; Lim, Jaehyok; Lee, Doo-Yong; Rassame, Somboon; Hibiki, Takashi; Ishii, Mamoru

2013-01-01

Highlights: ► Counterpart tests were performed on two large-scale BWR integral facilities. ► Similarity of post-LOCA system behaviors observed between two tests. ► Passive core and containment cooling systems work as design in both tests. -- Abstract: A counterpart test to the Passive Nachwärmeabfuhr und Druckabbau Test Anlage (Passive Decay Heat Removal and Depressurization Test Facility, PANDA) International Standard Problem (ISP)-42 test was conducted at the Purdue University Multi-Dimensional Integral Test Assembly (PUMA) facility. Aimed to support code validation on a range of light water reactor (LWR) containment issues, the ISP-42 test consists of six sequential phases (Phases A–F) with separately defined initial and boundary conditions, addressing different stages of anticipated accident scenario and system responses. The counterpart test was performed from Phases A to D, which are within the scope of the normal integral tests performed on the PUMA facility. A scaling methodology was developed by using the PANDA facility as prototype and PUMA facility as test model, and an engineering scaling has been applied to the PUMA facility. The counterpart test results indicated that functions of passive safety systems, such as passive containment cooling system (PCCS) start-up, gravity-driven cooling system (GDCS) discharge, PCCS normal operation and overload function were confirmed in both the PANDA and PUMA facilities with qualitative similarities

PUMA and NF-kB Are Cell Signaling Predictors of Reovirus Oncolysis of Breast Cancer.

Science.gov (United States)

Thirukkumaran, Chandini; Shi, Zhong-Qiao; Thirukkumaran, Ponnampalam; Luider, Joanne; Kopciuk, Karen; Spurrell, Jason; Elzinga, Kate; Morris, Don

2017-01-01

Reovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour. In the present study global gene expression profiling was utilized as a preliminary roadmap to tease-out pivotal molecules involved in reovirus induced apoptosis in breast cancer. Reovirus treated HTB133 and MCF7 breast cancer cells revealed transcriptional alteration of a defined subset of apoptotic genes and members of the nuclear factor-kappa B (NF-kB) family and p53 upregulated modulator of apoptosis (PUMA) were prominent. Since NF-kB can paradoxically suppress or promote apoptosis in cancer, the significance of NF-kB in reovirus oncolysis of breast cancer was investigated. Real time PCR analysis indicated a 2.9-4.3 fold increase in NF-kB p65 message levels following reovirus infection of MCF7 and HTB133, respectively. Nuclear translocation of NF-kB p65 protein was also dramatically augmented post reovirus treatment and correlated with enhanced DNA binding. Pharmacologic inhibition of NF-kB lead to oncolytic protection and significant down regulation of PUMA message levels. PUMA down regulation using siRNA suppressed reovirus oncolysis via significantly repressed apoptosis in p53 mutant HTB133 cells. This study demonstrates for the first time that a prominent pathway of reovirus oncolysis of breast cancer is mediated through NF-kB and that PUMA upregulation is dependent on NF-kB activation. These findings represent potential therapeutic indicators of reovirus treatment in future clinical trials.

PUMAS (Practical Uses of Math And Science) - Low Cost, High Impact

Science.gov (United States)

Kahn, R. A.

2004-12-01

PUMAS is an on-line journal, aimed at giving pre-college teachers brief examples showing how math and science topics taught in K-12 classes can be used in interesting settings, including everyday life. The concept is a simple one - (1) ask scientists, engineers, and other content experts to write up their favorite examples of practical uses, (2) ask the authors to key their examples to the National Standards and Benchmarks, so the material is grade-appropriate and useful in the classroom, (3) have each example peer-reviewed by at least one scientist with a relevant background, and at least one teacher at an appropriate grade level, helping keep an emphasis on quality, and (4) disseminate the examples widely and inexpensively through the PUMAS Web Site (http://pumas.jpl.nasa.gov). PUMAS examples may be activities, anecdotes, descriptions of "neat ideas," formal exercises, puzzles, or demonstrations; each one is a gem, written in the voice of its author. The PUMAS site also provides opportunities for feedback on individual examples and on the journal as a whole. As with most scientific journals, the writing, reviewing, and editing efforts are volunteered; they leverage the "community service" offered by so many teachers and scientists. We have streamlined all aspects of the example submission, review, and search processes so participants can contribute at a high level, with a minimum of extraneous effort. The primary PUMAS operating expenses cover Web Site technical maintenance and computer security. The PUMAS site receives several thousand unique queries per week, and publishes an average of about one new example per month. Maintaining a strong user base has been helped by endorsements from such organizations as the NSTA and NCTM. To contributors we offer an avenue for making a real impact on pre-college education with a relatively small time commitment, and the opportunity for peer-reviewed publication. We are always looking for good examples of the Practical Uses

Bax regulates neuronal Ca2+ homeostasis.

Science.gov (United States)

D'Orsi, Beatrice; Kilbride, Seán M; Chen, Gang; Perez Alvarez, Sergio; Bonner, Helena P; Pfeiffer, Shona; Plesnila, Nikolaus; Engel, Tobias; Henshall, David C; Düssmann, Heiko; Prehn, Jochen H M

2015-01-28

Excessive Ca(2+) entry during glutamate receptor overactivation ("excitotoxicity") induces acute or delayed neuronal death. We report here that deficiency in bax exerted broad neuroprotection against excitotoxic injury and oxygen/glucose deprivation in mouse neocortical neuron cultures and reduced infarct size, necrotic injury, and cerebral edema formation after middle cerebral artery occlusion in mice. Neuronal Ca(2+) and mitochondrial membrane potential (Δψm) analysis during excitotoxic injury revealed that bax-deficient neurons showed significantly reduced Ca(2+) transients during the NMDA excitation period and did not exhibit the deregulation of Δψm that was observed in their wild-type (WT) counterparts. Reintroduction of bax or a bax mutant incapable of proapoptotic oligomerization equally restored neuronal Ca(2+) dynamics during NMDA excitation, suggesting that Bax controlled Ca(2+) signaling independently of its role in apoptosis execution. Quantitative confocal imaging of intracellular ATP or mitochondrial Ca(2+) levels using FRET-based sensors indicated that the effects of bax deficiency on Ca(2+) handling were not due to enhanced cellular bioenergetics or increased Ca(2+) uptake into mitochondria. We also observed that mitochondria isolated from WT or bax-deficient cells similarly underwent Ca(2+)-induced permeability transition. However, when Ca(2+) uptake into the sarco/endoplasmic reticulum was blocked with the Ca(2+)-ATPase inhibitor thapsigargin, bax-deficient neurons showed strongly elevated cytosolic Ca(2+) levels during NMDA excitation, suggesting that the ability of Bax to support dynamic ER Ca(2+) handling is critical for cell death signaling during periods of neuronal overexcitation. Copyright © 2015 the authors 0270-6474/15/351706-17$15.00/0.

Suberoyl bis-hydroxamic acid induces p53-dependent apoptosis of MCF-7 breast cancer cells

Institute of Scientific and Technical Information of China (English)

Zhi-gang ZHUANG; Fei FEI; Ying CHEN; Wei JIN

2008-01-01

Aim: To study the effects of suberoyl bis-hydroxamic acid (SBHA), an inhibitor of histone deacetylases, on the apoptosis of MCF-7 breast cancer cells. Meth-ods: Apoptosis in MCF-7 cells induced by SBHA was demonstrated by flow cytometric analysis, morphological observation, and DNA ladder. Mitochondrial membrane potential (△ψm) was measured using the fluorescent probe JC-1. The expressions of p53, p21, Bax, and PUMA were determined using RT-PCR or Western blotting analysis after the MCF-7 cells were treated with SBHA or p53 siRNA. Results: SBHA induced apoptosis in MCF-7 cells. The expressions of p53, p21, Bax, and PUMA were induced, and △ψm collapsed after treatment with SBHA. p53 siRNA abrogated the SBHA-induced apoptosis and the expressions of p53, p21, Bax, and PUMA. Conclusion: The activation of the p53 pathway is involved in SBHA-induced apoptosis in MCF-7 cells.

Using Species Distribution Models to Predict Potential Landscape Restoration Effects on Puma Conservation.

Science.gov (United States)

Angelieri, Cintia Camila Silva; Adams-Hosking, Christine; Ferraz, Katia Maria Paschoaletto Micchi de Barros; de Souza, Marcelo Pereira; McAlpine, Clive Alexander

2016-01-01

A mosaic of intact native and human-modified vegetation use can provide important habitat for top predators such as the puma (Puma concolor), avoiding negative effects on other species and ecological processes due to cascade trophic interactions. This study investigates the effects of restoration scenarios on the puma's habitat suitability in the most developed Brazilian region (São Paulo State). Species Distribution Models incorporating restoration scenarios were developed using the species' occurrence information to (1) map habitat suitability of pumas in São Paulo State, Southeast, Brazil; (2) test the relative contribution of environmental variables ecologically relevant to the species habitat suitability and (3) project the predicted habitat suitability to future native vegetation restoration scenarios. The Maximum Entropy algorithm was used (Test AUC of 0.84 ± 0.0228) based on seven environmental non-correlated variables and non-autocorrelated presence-only records (n = 342). The percentage of native vegetation (positive influence), elevation (positive influence) and density of roads (negative influence) were considered the most important environmental variables to the model. Model projections to restoration scenarios reflected the high positive relationship between pumas and native vegetation. These projections identified new high suitability areas for pumas (probability of presence >0.5) in highly deforested regions. High suitability areas were increased from 5.3% to 8.5% of the total State extension when the landscapes were restored for ≥ the minimum native vegetation cover rule (20%) established by the Brazilian Forest Code in private lands. This study highlights the importance of a landscape planning approach to improve the conservation outlook for pumas and other species, including not only the establishment and management of protected areas, but also the habitat restoration on private lands. Importantly, the results may inform environmental

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

Science.gov (United States)

Darling, Nicola J; Balmanno, Kathryn; Cook, Simon J

2017-01-01

Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

Directory of Open Access Journals (Sweden)

Nicola J Darling

Full Text Available Disruption of protein folding in the endoplasmic reticulum (ER causes ER stress. Activation of the unfolded protein response (UPR acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2 signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

Organic chemistry of cometary dust as derived from PUMA 1 data

Science.gov (United States)

Kissel, J.; Krueger, F. R.

1989-01-01

Onboard the Halley Fly-By spacecrafts Vega 1, Vega 2, and Giotto were the dust impact mass spectrometers PUMA 1, PUMA 2, and PIA respectively. PUMA 1 was the most sensitive instrument among them. From its data the occurrence of masslines greater than 60 Daltons could be shown to be statistically significant. An analysis of these masslines lead to a scenario, which could explain the masslines as fragment ions from larger molecules which characterize the chemical nature of cometary organic matter as: (1) highly unsaturated hydrocarbons; (2) some of them containing oxygen; (3) less containing nitrogen; and (4) a few containing oxygen and nitrogen as heteroatoms. From the properties of the spectrometer, also some physical parameters of the dust particles could be inferred, such as their density and structure.

Energetics and evasion dynamics of large predators and prey: pumas vs. hounds.

Science.gov (United States)

Bryce, Caleb M; Wilmers, Christopher C; Williams, Terrie M

2017-01-01

Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs ( Canis lupus familiaris , 26 kg, n  = 4-5 per chase) pursuing simultaneously instrumented solitary pumas ( Puma concolor , 60 kg, n  = 2). We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides) as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns) to increase their escape distance from the overall faster hounds (avg. 2.3× faster). These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg -1  min -1 , respectively). On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted [Formula: see text] and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids.

Energetics and evasion dynamics of large predators and prey: pumas vs. hounds

Directory of Open Access Journals (Sweden)

Caleb M. Bryce

2017-08-01

Full Text Available Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs (Canis lupus familiaris, 26 kg, n = 4–5 per chase pursuing simultaneously instrumented solitary pumas (Puma concolor, 60 kg, n = 2. We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns to increase their escape distance from the overall faster hounds (avg. 2.3× faster. These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg−1 min−1, respectively. On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted $\\dot {\\mathrm{V }}{\\mathrm{O}}_{2\\mathrm{MAX}}$ V ̇ O 2 MAX and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids.

Radiosensitization effect of recombinant adenoviral-mediated PUMA gene on pancreatic carcinoma cells

International Nuclear Information System (INIS)

Zhu Dongming; Zhang Kejun; Li Dechun; Zhu Xuefeng; Yang Yong

2009-01-01

Objective: To study the effect of PUMA gene mediated by recombinant adenovirus vector combined with radiation on the pancreatic carcinoma. Methods: The PANC-1 cells were infected with Ad- PUMA (MOI=10, 50 and 100, respectively) for 48 h. The expression of PUMA mRNA and protein was detected by RT-PCR and Western blot, respectively. PANC-1 cells were divided into 4 groups: control group, transfection group, irradiation group and combined treatment group. The cell growth inhibition rate and apoptotic rate of PANC-1 cells were assessed by MTT assay and flow cytometry. Human pancreatic carcinomas were transplanted subcutaneously in nude mice, which were randomized into 4 groups: control group, transfection group, irradiation group and combined treatment group. Tumor growth rate and apoptotic index at different time points were recorded in 35 days. Results: The expression of PUMA mRNA and protein was increased with the increase of MOI of Ad-PUMA, which was does-dependant (MOI=10, mRNA=0.46± 0.02, protein=0.75± 0.09; MOI=50, mRNA=1.12±0.09, protein=1.01±0.18; MOI=100, mRNA=1.50±0.08, protein= 1.80±0.15; P 3 , (39.5±9.23)mm 3 , (33.6±10.3)mm 3 and (52.0±11.43)mm 3 , respectively, P<0.05]. And the apoptotic index was increased in the same manner (AI=0.43±0.05, 0.29±0.10, 0.24±0.05 and 0.00±0.00, respectively, P<0.05). Conclusions: Recombinant adenoviral-mediated PUMA gene combined with irradiation could increase the cell-killing effect on pancreatic carcinoma. It is better than that of either one kind of therapy. (authors)

The Perception of the PUMA Brand in the Czech Market

OpenAIRE

Martínková, Kateřina

2017-01-01

The ambition of this master thesis is to provide a deeper insight into a marketing strategy of the multinational company PUMA applied in the Czech Republic. Specifically, the thesis includes a survey of customers designed to examine the perception of the PUMA brand in the Czech market within the target group of people from 16 to 26 years old. One of the essential requirements of this thesis is to provide a very important theoretical background of the marketing field, explaining the basic mark...

Marketingový výzkum hodnoty značky Puma

OpenAIRE

Lhota, Filip

2011-01-01

My thesis introduces a problem of value identification concerning the brand Puma in the Czech Republic. The main objective of this thesis is to find out how is Puma perceived by the Czech population as well as how satisfied and familiar is the Czech population with its products. The theoretical part of the thesis will deal with obtaining information and defining terms in field of marketing research, brand value and propagation. The practical part will include data collection and its processin...

Analýza vývoje sportovních značek (Adidas a Puma)

OpenAIRE

Cajzl, Jan

2014-01-01

Title: Analysis of development of sports brands Adidas and Puma Objectives: The main aim of this thesis is to compile, describe and analyze informations about history and development of sports brands Adidas and Puma. Methods: The main informations obout historical development of Adidas and Puma were processed by direct historical method, method of deduction and progressive method. Research through the comparative method was used marginally. Results: The results show the direction in which the...

Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.

Science.gov (United States)

Xiong, Hui; Zhang, Jiangnan

2017-12-01

The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (PATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

A New Tool for CME Arrival Time Prediction using Machine Learning Algorithms: CAT-PUMA

Science.gov (United States)

Liu, Jiajia; Ye, Yudong; Shen, Chenglong; Wang, Yuming; Erdélyi, Robert

2018-03-01

Coronal mass ejections (CMEs) are arguably the most violent eruptions in the solar system. CMEs can cause severe disturbances in interplanetary space and can even affect human activities in many aspects, causing damage to infrastructure and loss of revenue. Fast and accurate prediction of CME arrival time is vital to minimize the disruption that CMEs may cause when interacting with geospace. In this paper, we propose a new approach for partial-/full halo CME Arrival Time Prediction Using Machine learning Algorithms (CAT-PUMA). Via detailed analysis of the CME features and solar-wind parameters, we build a prediction engine taking advantage of 182 previously observed geo-effective partial-/full halo CMEs and using algorithms of the Support Vector Machine. We demonstrate that CAT-PUMA is accurate and fast. In particular, predictions made after applying CAT-PUMA to a test set unknown to the engine show a mean absolute prediction error of ∼5.9 hr within the CME arrival time, with 54% of the predictions having absolute errors less than 5.9 hr. Comparisons with other models reveal that CAT-PUMA has a more accurate prediction for 77% of the events investigated that can be carried out very quickly, i.e., within minutes of providing the necessary input parameters of a CME. A practical guide containing the CAT-PUMA engine and the source code of two examples are available in the Appendix, allowing the community to perform their own applications for prediction using CAT-PUMA.

Hábitos alimentarios del Puma concolor (Carnivora: Felidae en el Parque Nacional Natural Puracé, Colombia

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Andrés Hernández-Guzmán

2011-09-01

Full Text Available La dieta de Puma concolor es ampliamente conocida a lo largo de su distribución, sin embargo, en Colombia no se ha realizado ningún estudio sobre sus hábitos alimentarios. Entre 2007-2009, la dieta de puma fue analizada en el Parque-Nacional-Natural-Puracé, sur occidente de los Andes colombianos. Ítems alimenticios de cinco especies presa fueron identificadas en su dieta; el venado conejo (Pudu mephistophiles es la presa más importante. Como herramienta complementaria para la identificación de huesos y pelos contenidos en heces (n=60, se instalaron seis cámarastrampa en lugares estratégicos, para registrar la presencia de pumas y presas potenciales. El descubrimiento de la dependencia de los pumas con el pudú sugiere una única adaptación de los pumas de paramo a la disponibilidad de presas y resalta su importancia como reguladores de las poblaciones presa. Estos resultados contribuyen a incrementar el poco conocimiento sobre la ecología de pumas de los Andes, de sus presas y de las especies en su conjunto en Colombia. Obtener información sobre el grupo de presas de pumas en diferentes ecosistemas, es esencial para entender los requerimientos regionales para su supervivencia y diseñar acciones de conservación que permitan seguir/evaluar las necesidades particulares de áreas protegidas en toda su distribución.

Evaluating public participation exercises - PUMA findings

International Nuclear Information System (INIS)

Vergez, Christian; )

2003-01-01

A programme of work was undertaken under the auspices of the PUMA (Public Management Project) Working Group on Strengthening Government-Citizen Connections during 1999-2000. Two comparative surveys were conducted among 23 OECD member countries and the European Union, and eight in-depth country cases were performed; the results were discussed in five meetings and published as 'OECD PUMA, 2001'. While the benefits of engaging citizens in policy-making may be considerable, governments should not underestimate the risks associated with poorly designed and inadequate measures for information, consultation and active participation. They may seek to inform, consult and encourage active participation by citizens in order to enhance the quality, credibility and legitimacy of their policy decisions. However the opposite effect may be achieved if citizens discover that their efforts to be informed, provide feedback and actively participate are ignored or have no impact at all on the decisions reached. To reduce the risk of rapid disillusionment and further erosion of citizens' trust, governments must ensure that: - information is complete, objective, reliable, relevant, easy to find and understand; - consultation is conducted with clear goals and according to unambiguous rules which clearly state the limits of the exercise and government's obligation to account for the use made of citizens' input; - participation provides sufficient time and flexibility to allow for the emergence of new ideas and proposals on the part of citizens and a mechanism for their integration into government's policy-making process. Yet the comparative study performed by PUMA found that evaluation was often overlooked. There is a striking imbalance between the amount of time, money and energy which OECD Member countries invest in strengthening government-citizen connections and their efforts to evaluate the effectiveness of these measures and their impact on public policy-making

Juan Puma, el hijo del oso. Cuento quechua de La Jalca, Chachapoyas

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1997-01-01

Full Text Available JUAN PUMA, LE FILS DE L'OURS . CONTE QUECHUA DE LA JALCA, CHACHAPOYAS. Une des fêtes les plus importantes de la communauté de La Jalca, Province de Chachapoyas, Amazonas, est celle de la Saint-Pierre où l’on exécute une danse de l’ours très semblable à celle des ukukus du sud péruvien. Le narrateur du récit que nous publions ici assimile ce rite à l’histoire de Juan Oso (Jean de l’Ours très connue dans le monde andin. L’importance de l’ours dans cette culture des hautes terres amazoniennes est fondamentale. En quechua local, l’ours s’appelle “puma” et partage avec le puma de la forêt les caractéristiques de puissance effrayante et de pouvoirs surnaturels. Le fils de l’ours, Juan, évoque les relations ambiguës liant les “chrétiens” des hautes terres d’Amazonas et les “sauvages” de la forêt. Una de las fiestas más importantes de la comunidad de La Jalca, Provincia de Chachapoyas, Amazonas, es la de San Pedro en la que se representa un baile del oso muy semejante al baile de los ukukus del sur peruano. El narrador del cuento que publicamos aquí asimila este rito a la historia de Juan Oso, muy conocido en el mundo andino. La importancia del oso en esta cultura de la ceja de selva alta es fundamental. En quechua local, el oso se llama “puma” y comparte con el puma de la selva las características de fuerza temible y poderes sobrenaturales. El hijo del oso, Juan, evoca las relaciones ambiguas existentes entre los “cristianos” de la serranía de Amazonas y los “chunchos” de la selva. JUAN PUMA, THE BEAR'S SON. A QUECHUA TALE FROM LA JALCA, CHACHAPOYAS. One of the most important feasts of the community of La Jalca, Province of Amazonas, is that of Saint Peter in which a bear dance similar to the southern Peruvian dance of the ukukus is performed. In the story published here, the narrator assimilates this rite with the tale of Juan Oso, another story which is well known throughout the Andes. The importance of bears

BAX protein expression and clinical outcome in epithelial ovarian cancer.

Science.gov (United States)

Tai, Y T; Lee, S; Niloff, E; Weisman, C; Strobel, T; Cannistra, S A

1998-08-01

Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer. BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed. BAX protein was expressed at high levels (defined as > or = 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P = .036). After a median follow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P = .0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified. The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel.

PUMAS: The On-line journal of Math and Science Examples for Pre-College Education

Science.gov (United States)

Trainer, Melissa G.; Kahn, Ralph A.

2015-11-01

PUMAS - “Practical Uses of Math And Science” - is an on-line collection of brief examples showing how math and science topics taught in K-12 classes can be used in interesting settings, including every day life. The examples are written primarily by scientists, engineers, and other content experts having practical experience with the material. They are aimed mainly at classroom teachers to enrich their presentation of math and science topics. The goal of PUMAS is to capture, for the benefit of pre-college education, the flavor of the vast experience that working scientists have with interesting and practical uses of math and science. There are currently over 80 examples in the PUMAS collection, and they are organized by curriculum topics and tagged with relevant grade levels and curriculum topic benchmarks. The published examples cover a wide range of subject matter: from demonstrating why summer is hot, to describing the fluid dynamics of a lava lamp, to calculating the best age to collect Social Security Benefits. The examples are available to all interested parties via the PUMAS web site: http://pumas.nasa.gov/.We invite the community to participate in the PUMAS collection. We seek scientists and scientific thinkers to provide innovative examples of practical uses for teachers to use to enrich the classroom experience, and content experts to participate in peer-review. We also seek teachers to review examples for originality, accuracy of content, clarity of presentation, and grade-level appropriateness. Finally, we encourage teachers to mine this rich repository for real-world examples to demonstrate the value of math in science in everyday life.

miR-34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA.

Science.gov (United States)

Zhang, Qing-An; Yang, Xu-Hai; Chen, Dong; Yan, Xiang; Jing, Fu-Chun; Liu, Hong-Qian; Zhang, Ronghua

2018-01-01

miR-34 was deregulated in tumor tissues compared with corresponding noncancerous tissue samples. Furthermore, miR-34 may contribute to cancer-stromal interaction associated with cancer progression. However, whether miR-34 could decrease chemoresistance of cancer cells to chemotherapeutic agent remains unclear. In our study, we examined whether overexpression of miR-34 could sensitize gemcitabine -mediated apoptosis in human pancreatic cancer PANC-1 cells. We found that miR-34 markedly induced gemcitabine -mediated apoptosis in PANC-1 cells. miR-34 induced down-regulation of Slug expression and upregulation of p53 up-regulated modulator of apoptosis (PUMA) expression. The over-expression of Slug or downregulation of PUMA by Slug cDNA or PUMA siRNA transfection markedly blocked miR-34-induced gemcitabine sensitization. Furthermore, miR-34 induced PUMA expression by downregulation of Slug. Taken together, our study demonstrates that miR-34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.

Mitochondrial ceramide-rich macrodomains functionalize Bax upon irradiation.

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Hyunmi Lee

Full Text Available Evidence indicates that Bax functions as a "lipidic" pore to regulate mitochondrial outer membrane permeabilization (MOMP, the apoptosis commitment step, through unknown membrane elements. Here we show mitochondrial ceramide elevation facilitates MOMP-mediated cytochrome c release in HeLa cells by generating a previously-unrecognized mitochondrial ceramide-rich macrodomain (MCRM, which we visualize and isolate, into which Bax integrates.MCRMs, virtually non-existent in resting cells, form upon irradiation coupled to ceramide synthase-mediated ceramide elevation, optimizing Bax insertion/oligomerization and MOMP. MCRMs are detected by confocal microscopy in intact HeLa cells and isolated biophysically as a light membrane fraction from HeLa cell lysates. Inhibiting ceramide generation using a well-defined natural ceramide synthase inhibitor, Fumonisin B1, prevented radiation-induced Bax insertion, oligomerization and MOMP. MCRM deconstruction using purified mouse hepatic mitochondria revealed ceramide alone is non-apoptogenic. Rather Bax integrates into MCRMs, oligomerizing therein, conferring 1-2 log enhanced cytochrome c release. Consistent with this mechanism, MCRM Bax isolates as high molecular weight "pore-forming" oligomers, while non-MCRM membrane contains exclusively MOMP-incompatible monomeric Bax.Our recent studies in the C. elegans germline indicate that mitochondrial ceramide generation is obligate for radiation-induced apoptosis, although a mechanism for ceramide action was not delineated. Here we demonstrate that ceramide, generated in the mitochondrial outer membrane of mammalian cells upon irradiation, forms a platform into which Bax inserts, oligomerizes and functionalizes as a pore. We posit conceptualization of ceramide as a membrane-based stress calibrator, driving membrane macrodomain organization, which in mitochondria regulates intensity of Bax-induced MOMP, and is pharmacologically tractable in vitro and in vivo.

Driving p53 Response to Bax Activation Greatly Enhances Sensitivity to Taxol by Inducing Massive Apoptosis

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Paola De Feudis

2000-05-01

Full Text Available The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3 were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53

Science.gov (United States)

Charvet, Céline; Wissler, Manuela; Brauns-Schubert, Prisca; Wang, Shang-Jui; Tang, Yi; Sigloch, Florian C.; Mellert, Hestia; Brandenburg, Martin; Lindner, Silke E.; Breit, Bernhard; Green, Douglas R.; McMahon, Steven B.; Borner, Christoph; Gu, Wei; Maurer, Ulrich

2011-01-01

Summary Activation of p53 by DNA damage results in either cell cycle arrest, allowing DNA repair and cell survival, or induction of apoptosis. As these opposite outcomes are both mediated by p53 stabilization, additional mechanisms to determine this decision must exist. Here we show that glycogen synthase kinase-3 (GSK-3) is required for the p53-mediated induction of the pro-apoptotic BH3 only-protein PUMA, an essential mediator of p53-induced apoptosis. Inhibition of GSK-3 protected from cell death induced by DNA damage and promoted increased long-term cell survival. We demonstrate that GSK-3 phosphorylates serine 86 of the p53-acetyltransferase Tip60. A Tip60S86A mutant was less active to induce p53 K120 acetylation, Histone 4 acetylation and expression of PUMA. Our data suggest that GSK-3 mediated Tip60S86-phosphorylation provides a link between PI3K signaling and the choice for or against apoptosis induction by p53. PMID:21658600

p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis.

Science.gov (United States)

Wang, Wei; Liu, Haijun; Dai, Xiaoniu; Fang, Shencun; Wang, Xingang; Zhang, Yingming; Yao, Honghong; Zhang, Xilong; Chao, Jie

2015-11-18

Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and PUMA protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and PUMA expression; and 3) RNA interference targeting p53 and PUMA prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/PUMA expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/PUMA in the development of novel therapeutic strategies for silicosis treatment.

CSR och politisk konsumtion : - en studie av Nikes och Pumas CSR- rapporter

OpenAIRE

Björling, Ameli

2010-01-01

“CSR and political consumption – a study of Nike’s and Puma’s CSR-reports” The purpose of this dissertation is to examine if political consumption has influenced multinational corporations to improve their Corporate Social Responsibility reports and policies more, than a company who has not been a target for political consumption. This dissertation is a content analysis of Nike’s and Puma’s first (Nike 2001, Puma 2001) and latest (Nike 2007/09, Puma 2007/08) CSR- reports. Archie Carroll’s mod...

Puma and Trail/Dr5 Pathways Control Radiation-Induced Apoptosis in Distinct Populations of Testicular Progenitors

International Nuclear Information System (INIS)

Coureuil, M.; Tavernier, M.; Barroca, V.; Fouchet, P.; Allemand, I.; Ugolin, N.; Chevillard, S.

2010-01-01

Spermatogonia- stem cells and progenitors of adult spermatogenesis- are killed through a p53-regulated apoptotic process after γ-irradiation but the death effectors are still poorly characterized. Our data demonstrate that both intrinsic and extrinsic apoptotic pathways are involved, and especially that spermatogonia can be split into two main populations, according to apoptotic effectors. Following irradiation both Dr5 and Puma genes are up-regulated in the α 6 -integrin-positive Side Population (SP) fraction, which is highly enriched in spermatogonia. Flow cytometric analysis confirms an increased number of Dr5-expressing SP cells, and Puma-β isoform accumulates in α 6 -integrin positive cellular extracts, enriched in spermatogonia. Trail -/- or Puma -/- spermatogonia display a reduced sensitivity to radiation-induced apoptosis. The TUNEL kinetics strongly suggest that the extrinsic and intrinsic pathways, via Trail/Dr5 and Puma respectively, could be engaged in distinct subpopulations of spermatogonia. Indeed flow cytometric studies show that Dr5 receptor is constitutively present on more than half of the undifferentiated progenitors (Kit - α 6 + SP) and half of the differentiated ones (Kit + α 6 + SP). In addition after irradiation, Puma is not detected in the Dr5-positive cellular fraction isolated by immuno-magnetic purification, while Puma is present in the Dr5-negative cell extracts. In conclusion, adult testicular progenitors are divided into distinct sub-populations by apoptotic effectors, independently of progenitor types (immature Kit-negative versus mature Kit-positive), underscoring differential radiosensitivities characterizing the stem cell/progenitors compartment. (authors)

Geological map of Uruguay Esc 1,100,000. Fuente del Puma Sheet G-27

International Nuclear Information System (INIS)

Preciozzi, F.; Pena, S.

1990-01-01

This work is about the geological map of Uruguay Esc.1.100.000 (Fuente del Puma) and the explanatory memoranda which describes the geological , lithological and sedimentological characteristics soils. The area corresponding to Fuente del Puma is located in the SW of Lavalleja and NW of Maldonado town and its stratigraphy belong to the Cretaceous and Cenozoic formations as well as the Cambrian and upper Precambrian

New light on an old friend: targeting PUMA in radioprotection and therapy of cardiovascular and neurodegenerative diseases.

Science.gov (United States)

Tichy, Ales; Marek, Jan; Havelek, Radim; Pejchal, Jaroslav; Seifrtova, Martina; Zarybnicka, Lenka; Filipova, Alzbeta; Rezacova, Martina; Sinkorova, Zuzana

2018-04-05

This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53-independent induction is described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with overview of other therapeutic applications. Finally, basic chemical structures for development of novel PUMA modulators such as pifithrine derivativeses, kinase inhibitors or modulators of Bcl-2 protein family are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Značky Adidas a Puma v letech 2006-08 : komparativní studie

OpenAIRE

Suchá, Helena

2010-01-01

The bachelor thesis "Adidas and Puma brands in the years 2006-2008 : comparative study " deals with comparing the positioning and communication activities of Adidas and Puma sport brands in the years 2006-2008 in both Czech and Global market for sporting goods. Their Sharp origin and history is reflected in the production and marketing communication of brands that belong to the leaders in the sports industry and sponsorships. The first two parts deal with representation of brands Adidas and P...

PUMA Internet Task Logging Using the IDAC-1

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K. N. Tarchanidis

2014-08-01

Full Text Available This project uses an IDAC-1 board to sample the joint angle position of the PUMA 76 1 robot and log the results on a computer. The robot is at the task location and the logging computer is located in a different one. The task the robot is performing is based on a Pseudo Stereo Vision System (PSVS. Internet is the transport media. The protocol used in this project is UDP/IP. The actual angle is taken straight from the PUMA controller. High-resolution potentiometers are connected on each robot joint and are buffered and sampled as potential difference on an A/D converter integrated on the IDAC-1. The logging computer through the Internet acting as client asks for the angle set, the IDAC-1 responds as server with the 10-bit resolution sampling of the joint position. The whole task is logged in a file on the logging computer. This application can give the ability to the Internet user to monitor and log the robot tasks anywhere in the Word Wide Web (www.

EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing's Sarcoma.

Science.gov (United States)

Hossain, Mohammad Motarab; Ray, Swapan Kumar

2014-10-01

Ewing's sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing's sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing's sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing's sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing's sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing's sarcoma in cell culture and animal models.

A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca, Pumas (Puma concolor, and Ocelots (Leopardus pardalis in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

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Claudia Wultsch

Full Text Available With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca, pumas (Puma concolor, and ocelots (Leopardus pardalis. We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09, followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16, and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08. We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells

International Nuclear Information System (INIS)

Mahyar-Roemer, Mojgan; Köhler, Hans; Roemer, Klaus

2002-01-01

The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax. The expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated. Low to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells. Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies

Reduced expression of bax in small cell lung cancer cells is not sufficient to induce cisplatin-resistance

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Biagosch J

2010-10-01

Full Text Available Abstract Resistance to cisplatin in the course of chemotherapy contributes to the poor prognosis of small cell lung cancer (SCLC. B cell lymphoma-2 is the founding member of a large family of proteins that either promote or inhibit apoptosis. We aimed at investigating if the pro-apoptotic members Bad, Bax, Bim and Bid are involved in cisplatin-resistance. Cisplatin-resistance in the SCLC cell line H1339 was induced by repetitive exposure to cisplatin. Protein expression was quantified by Western Blot and immuno-fluorescence analysis. Protein expression was altered using siRNA interference. Four "cycles" of 0.5 μg/ml cisplatin led to partial cisplatin-resistance in H1339 cells. The expression of Bad, Bim and Bid was comparable in naïve and resistant cells while the expression of Bax was reduced in the resistant clone. But, reducing Bax expression in naïve cells did not lead to altered cisplatin sensitivity neither in H1339 nor in H187 SCLC cells. We conclude that the reduced Bax expression after exposure to cisplatin is not sufficient to induce cis-platin-resistance in SCLC cells.

Expression of Bim, Noxa, and Puma in non-small cell lung cancer

International Nuclear Information System (INIS)

Sakakibara-Konishi, Jun; Oizumi, Satoshi; Kikuchi, Junko; Kikuchi, Eiki; Mizugaki, Hidenori; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu

2012-01-01

The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC). A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed. Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome. The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation

Filogeografia de Puma concolor (CARNIVORA, FELIDAE) na América do Sul

OpenAIRE

Eunice Moara Matte

2012-01-01

O felino Puma concolor, também conhecido por puma entre tantos outros nomes, é uma espécie de ampla distribuição no continente americano e está entre as 10 espécies de felídeos existentes na região Neotropical. Sua ampla distribuição e a história geológica das diferentes regiões ocupadas pela espécie ao longo de sua evolução agem diretamente na sua história evolutiva e demográfica. E muito do que aconteceu com a espécie, como expansões ou drásticas reduções demográficas, isolamento geográfico...

Trophic facilitation or limitation? Comparative effects of pumas and black bears on the scavenger community.

Science.gov (United States)

Allen, Maximilian L; Elbroch, L Mark; Wilmers, Christopher C; Wittmer, Heiko U

2014-01-01

Scavenging is a widespread behaviour and an important process influencing food webs and ecological communities. Large carnivores facilitate the movement of energy across trophic levels through the scavenging and decomposition of their killed prey, but competition with large carnivores is also likely to constrain acquisition of carrion by scavengers. We used an experimental approach based on motion-triggered video cameras at black-tailed deer (Odocoileus hemionus columbianus) carcasses to measure the comparative influences of two large carnivores in the facilitation and limitation of carrion acquisition by scavengers. We found that pumas (Puma concolor) and black bears (Ursus americanus) had different effects on their ecological communities. Pumas, as a top-level predator, facilitated the consumption of carrion by scavengers, despite significantly reducing their observed sum feeding times (165.7 min ± 21.2 SE at puma kills 264.3 min ± 30.1 SE at control carcasses). In contrast, black bears, as the dominant scavenger in the system, limited consumption of carrion by scavengers as evidenced by the observed reduction of scavenger species richness recorded at carcasses where they were present (mean = 2.33 ± 0.28 SE), compared to where they were absent (mean = 3.28 ± 0.23 SE). Black bears also had large negative effects on scavenger sum feeding times (88.5 min ± 19.8 SE at carcasses where bears were present, 372.3 min ± 50.0 SE at carcasses where bears were absent). In addition, we found that pumas and black bears both increased the nestedness (a higher level of order among species present) of the scavenger community. Our results suggest that scavengers have species-specific adaptions to exploit carrion despite large carnivores, and that large carnivores influence the structure and composition of scavenger communities. The interactions between large carnivores and scavengers should be considered in future studies of food webs and ecological communities.

A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

DEFF Research Database (Denmark)

Kampranis, S C; Damianova, R; Atallah, M

2000-01-01

The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows...... for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class theta glutathione S-transferases. This Bax-inhibiting (BI) protein was expressed...... in Escherichia coli and found to possess glutathione S-transferase (GST) and weak glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane...

Anatomical study of the forearm and hand nerves of the domestic cat ( Felis catus), puma ( Puma concolor) and jaguar ( Panthera onca).

Science.gov (United States)

Sánchez, H L; Silva, L B; Rafasquino, M E; Mateo, A G; Zuccolilli, G O; Portiansky, E L; Alonso, C R

2013-04-01

The innervation of the forearm and hand regions of cats has not been well described despite its importance for any surgery or any neurological disorder. It is probably the main area where disorders of peripheral nerves in this species are observed. In felines, the forelimbs facilitate the jump and represent the most important way for capturing prey. The main muscles and nerves involved in this activity are located in the region of the forearm and hand. The aim of the present study was to provide a detailed description of the innervation of the forearm and hand regions of the jaguar and puma, in comparison with that of the domestic cat, contributing thus with the anatomical knowledge of the area for applying it to surgery and pathology. The forearms of three pumas and two jaguars (all of them fixed in formalin) and of six domestic cats (fresh) were dissected. The nerves path and their forearm distribution patterns of all three species were described. The analysed results indicate that the observed variations between species are minimal; thus, the anatomy described for domestic cats can be widely applied to American wild felids. © 2012 Blackwell Verlag GmbH.

Universitätsbibliografie mit PUMA. Praxisbericht aus der Einführung der Universitätsbibliografie an der Universitätsbibliothek Stuttgart

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Sibylle Hermann

2017-12-01

The added value of the Academic Publication Management PUMA at the University of Stuttgart compared to a bibliographic cataloguing environment lies in the direct processing of data by scientists without an interim step via the library. For the university content management system, a plugin is available, which dynamically integrates publication lists into employees’ web pages. The metadata is loaded directly from PUMA, filtered, sorted and can be put out in the citation style desired. PUMA offers many interfaces and display possibilities.

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

Science.gov (United States)

Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

2015-08-01

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

Behavioral response races, predator-prey shell games, ecology of fear, and patch use of pumas and their ungulate prey.

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Laundré, John W

2010-10-01

The predator-prey shell game predicts random movement of prey across the landscape, whereas the behavioral response race and landscape of fear models predict that there should be a negative relationship between the spatial distribution of a predator and its behaviorally active prey. Additionally, prey have imperfect information on the whereabouts of their predator, which the predator should incorporate in its patch use strategy. I used a one-predator-one-prey system, puma (Puma concolor)-mule deer (Odocoileus hemionus) to test the following predictions regarding predator-prey distribution and patch use by the predator. (1) Pumas will spend more time in high prey risk/low prey use habitat types, while deer will spend their time in low-risk habitats. Pumas should (2) select large forage patches more often, (3) remain in large patches longer, and (4) revisit individual large patches more often than individual smaller ones. I tested these predictions with an extensive telemetry data set collected over 16 years in a study area of patchy forested habitat. When active, pumas spent significantly less time in open areas of low intrinsic predation risk than did deer. Pumas used large patches more than expected, revisited individual large patches significantly more often than smaller ones, and stayed significantly longer in larger patches than in smaller ones. The results supported the prediction of a negative relationship in the spatial distribution of a predator and its prey and indicated that the predator is incorporating the prey's imperfect information about its presence. These results indicate a behavioral complexity on the landscape scale that can have far-reaching impacts on predator-prey interactions.

Circadian transitions in radiation dose-dependent augmentation of mRNA levels for DNA damage-induced genes elicited by accurate real-time RT-PCR quantification

International Nuclear Information System (INIS)

Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko

2010-01-01

Molecular mechanisms of intracellular response after DNA-damage by exposure to ionizing radiation have been studied. In the case of cells isolated from living body of human and experimental animals, alteration of the responsiveness by physiological oscillation such as circadian rhythm must be considered. To examine the circadian variation in the response of p53-responsible genes p21, mdm2, bax, and puma, we established a method to quantitate their mRNA levels with high reproducibility and accuracy based on real-time reverse transcription polymerase chain reaction (RT-PCR) and compared the levels of responsiveness in mouse hemocytes after diurnal irradiation to that after nocturnal irradiation. Augmentations of p21 and mdm2 mRNA levels with growth-arrest and of puma mRNA before apoptosis were confirmed by time-course experiment in RAW264.7, and dose-dependent increases in the peak levels of all the RNA were shown. Similarly, the relative RNA levels of p21, mdm2, bax, and puma per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also increased dose-dependently in peripheral blood and bone marrow cells isolated from whole-body-irradiated mice. Induction levels of all messages reduced by half after nighttime irradiation as compared with daytime irradiation in blood cells. In marrow cells, nighttime irradiation enhanced the p21 and mdm2 mRNA levels than daytime irradiation. No significant difference in bax or puma mRNA levels was observed between nighttime and daytime irradiation in marrow cells. This suggests that early-stage cellular responsiveness in DNA damage-induced genes is modulated between diurnal and nocturnal irradiation. (author)

Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

Science.gov (United States)

Li, Sheng-Mian; Yao, Shu-Kun; Yamamura, Nobuyoshi; Nakamura, Toshitsugu

2003-01-01

AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors. METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n = 21, carcinoma of ampulla of Vater: n = 6), and 10 cases of atypical dysplasia. Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity. RESULTS: The expression of Bcl-2 was observed in 10 out of 27 (37.0%) invasive carcinomas, 1 out of 10 dysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30% (3/10) in dysplasia, and 40% (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia, with no significant difference in Bcl-2 expression (P = 0.110), and significant difference in Bax expression (P = 0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P = 0.012). Bcl-2 expression was correlated to Bax expression (P = 0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype, grade of differentiation, or level of invasion. CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part, in the apoptotic activity in extrahepatic biliary carcinoma. PMID:14606101

Harnessing the p53-PUMA Axis to Overcome DNA Damage Resistance in Renal Cell Carcinoma

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Xiaoguang Zhou

2014-12-01

Full Text Available Resistance to DNA damage–induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC. This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage–induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA. We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage–induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients.

Three pathogens in sympatric populations of pumas, bobcats, and domestic cats: implications for infectious disease transmission.

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Sarah N Bevins

Full Text Available Anthropogenic landscape change can lead to increased opportunities for pathogen transmission between domestic and non-domestic animals. Pumas, bobcats, and domestic cats are sympatric in many areas of North America and share many of the same pathogens, some of which are zoonotic. We analyzed bobcat, puma, and feral domestic cat samples collected from targeted geographic areas. We examined exposure to three pathogens that are taxonomically diverse (bacterial, protozoal, viral, that incorporate multiple transmission strategies (vector-borne, environmental exposure/ingestion, and direct contact, and that vary in species-specificity. Bartonella spp., Feline Immunodeficiency Virus (FIV, and Toxoplasma gondii IgG were detected in all three species with mean respective prevalence as follows: puma 16%, 41% and 75%; bobcat 31%, 22% and 43%; domestic cat 45%, 10% and 1%. Bartonella spp. were highly prevalent among domestic cats in Southern California compared to other cohort groups. Feline Immunodeficiency Virus exposure was primarily associated with species and age, and was not influenced by geographic location. Pumas were more likely to be infected with FIV than bobcats, with domestic cats having the lowest infection rate. Toxoplasma gondii seroprevalence was high in both pumas and bobcats across all sites; in contrast, few domestic cats were seropositive, despite the fact that feral, free ranging domestic cats were targeted in this study. Interestingly, a directly transmitted species-specific disease (FIV was not associated with geographic location, while exposure to indirectly transmitted diseases--vector-borne for Bartonella spp. and ingestion of oocysts via infected prey or environmental exposure for T. gondii--varied significantly by site. Pathogens transmitted by direct contact may be more dependent upon individual behaviors and intra-specific encounters. Future studies will integrate host density, as well as landscape features, to better

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Science.gov (United States)

Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

2014-01-01

Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. PMID:24563225

Bax function in the absence of mitochondria in the primitive protozoan Giardia lamblia.

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Adrian B Hehl

Full Text Available Bax-induced permeabilization of the mitochondrial outer membrane and release of cytochrome c are key events in apoptosis. Although Bax can compromise mitochondria in primitive unicellular organisms that lack a classical apoptotic machinery, it is still unclear if Bax alone is sufficient for this, or whether additional mitochondrial components are required. The protozoan parasite Giardia lamblia is one of the earliest branching eukaryotes and harbors highly degenerated mitochondrial remnant organelles (mitosomes that lack a genome. Here we tested whether human Bax expressed in Giardia can be used to ablate mitosomes. We demonstrate that these organelles are neither targeted, nor compromised, by Bax. However, specialized compartments of the regulated secretory pathway are completely ablated by Bax. As a consequence, maturing cyst wall proteins that are sorted into these organelles are released into the cytoplasm, causing a developmental arrest and cell death. Interestingly, this ectopic cargo release is dependent on the carboxy-terminal 22 amino acids of Bax, and can be prevented by the Bax-inhibiting peptide Ku70. A C-terminally truncated Bax variant still localizes to secretory organelles, but is unable to permeabilize these membranes, uncoupling membrane targeting and cargo release. Even though mitosomes are too diverged to be recognized by Bax, off-target membrane permeabilization appears to be conserved and leads to cell death completely independently of mitochondria.

Trophic facilitation or limitation? Comparative effects of pumas and black bears on the scavenger community.

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Maximilian L Allen

Full Text Available Scavenging is a widespread behaviour and an important process influencing food webs and ecological communities. Large carnivores facilitate the movement of energy across trophic levels through the scavenging and decomposition of their killed prey, but competition with large carnivores is also likely to constrain acquisition of carrion by scavengers. We used an experimental approach based on motion-triggered video cameras at black-tailed deer (Odocoileus hemionus columbianus carcasses to measure the comparative influences of two large carnivores in the facilitation and limitation of carrion acquisition by scavengers. We found that pumas (Puma concolor and black bears (Ursus americanus had different effects on their ecological communities. Pumas, as a top-level predator, facilitated the consumption of carrion by scavengers, despite significantly reducing their observed sum feeding times (165.7 min ± 21.2 SE at puma kills 264.3 min ± 30.1 SE at control carcasses. In contrast, black bears, as the dominant scavenger in the system, limited consumption of carrion by scavengers as evidenced by the observed reduction of scavenger species richness recorded at carcasses where they were present (mean = 2.33 ± 0.28 SE, compared to where they were absent (mean = 3.28 ± 0.23 SE. Black bears also had large negative effects on scavenger sum feeding times (88.5 min ± 19.8 SE at carcasses where bears were present, 372.3 min ± 50.0 SE at carcasses where bears were absent. In addition, we found that pumas and black bears both increased the nestedness (a higher level of order among species present of the scavenger community. Our results suggest that scavengers have species-specific adaptions to exploit carrion despite large carnivores, and that large carnivores influence the structure and composition of scavenger communities. The interactions between large carnivores and scavengers should be considered in future studies of food webs and ecological communities.

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

Science.gov (United States)

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

mPUMA: a computational approach to microbiota analysis by de novo assembly of operational taxonomic units based on protein-coding barcode sequences.

Science.gov (United States)

Links, Matthew G; Chaban, Bonnie; Hemmingsen, Sean M; Muirhead, Kevin; Hill, Janet E

2013-08-15

Formation of operational taxonomic units (OTU) is a common approach to data aggregation in microbial ecology studies based on amplification and sequencing of individual gene targets. The de novo assembly of OTU sequences has been recently demonstrated as an alternative to widely used clustering methods, providing robust information from experimental data alone, without any reliance on an external reference database. Here we introduce mPUMA (microbial Profiling Using Metagenomic Assembly, http://mpuma.sourceforge.net), a software package for identification and analysis of protein-coding barcode sequence data. It was developed originally for Cpn60 universal target sequences (also known as GroEL or Hsp60). Using an unattended process that is independent of external reference sequences, mPUMA forms OTUs by DNA sequence assembly and is capable of tracking OTU abundance. mPUMA processes microbial profiles both in terms of the direct DNA sequence as well as in the translated amino acid sequence for protein coding barcodes. By forming OTUs and calculating abundance through an assembly approach, mPUMA is capable of generating inputs for several popular microbiota analysis tools. Using SFF data from sequencing of a synthetic community of Cpn60 sequences derived from the human vaginal microbiome, we demonstrate that mPUMA can faithfully reconstruct all expected OTU sequences and produce compositional profiles consistent with actual community structure. mPUMA enables analysis of microbial communities while empowering the discovery of novel organisms through OTU assembly.

Participatory development of incentives to coexist with jaguars and pumas.

Science.gov (United States)

Amit, Ronit; Jacobson, Susan K

2018-01-22

Reducing costs and increasing benefits for rural communities coexisting with large carnivores is necessary for conservation of jaguar (Panthera onca) and puma (Puma concolor). To design acceptable incentives, stakeholders must be involved in the process. We conducted an innovative, structured, group communication process based on a Delphi technique as a template for identifying potential incentives. Community workshops with 133 members of 7 communities and surveys with 25 multidisciplinary experts from government, nongovernmental organizations, and academia provided iterative data to design a plan of incentives through 4 rounds of discussion. The final product integrated 862 ideas into 6 types of incentives: organization of communities, mechanisms for improved dialogue, citizen technical assistance, green labeling for community products, payment for the ecosystem service of biodiversity, and an assessment of financial alternatives. We used quantitative and qualitative techniques to indicate support for decisions about the design of incentives, which reduced researcher subjectivity. The diverse incentives developed and the cooperation from multiple stakeholders resulted in an incentive plan that integrated issues of governance, equity, and social norms. © 2018 Society for Conservation Biology.

Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway

International Nuclear Information System (INIS)

Sun, Lihua; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Yang, Yang; Yang, Hua

2012-01-01

Highlights: ► Ang II-induced apoptosis in intestinal epithelial cell through AT2 receptor. ► The apoptosis process involves in the Bax/Bcl-2 intrinsic pathway. ► GATA-6 short hairpin RNA reduced Bax expression, but not Bcl-2. ► GATA-6 may play a critical role in apoptosis in response to the Ang II challenge. -- Abstract: Angiotensin II (Ang II) has been shown to play an important role in cell apoptosis. However, the mechanisms of Ang-II-induced apoptosis in intestinal epithelial cells are not fully understood. GATA-6 is a zinc finger transcription factor expressed in the colorectal epithelium, which directs cell proliferation, differentiation and apoptosis. In the present study we investigated the underlying mechanism of which GATA-6 affects Ang-II induced apoptosis in intestinal epithelial cells. The in vitro intestinal epithelial cell apoptosis model was established by co-culturing Caco-2 cells with Ang II. Pretreatment with Angiotensin type 2 (AT2) receptor antagonist, PD123319, significantly reduced the expression of Bax and prevented the Caco-2 cells apoptosis induced by Ang II. In addition, Ang II up-regulated the expression of GATA-6. Interestingly, GATA-6 short hairpin RNA prevented Ang II-induced intestinal epithelial cells apoptosis and reduced the expression of Bax, but not Bcl-2. Taken together, the present study suggests that Angiotensin II promotes apoptosis in intestinal epithelial cells through GATA-6 and the Bax pathway in an AT2 receptor-dependent manner.

High consumption of primates by pumas and ocelots in a remnant of the Brazilian Atlantic Forest

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JL Santos

Full Text Available We studied the diet of the ocelot and puma during the years 2007 and 2008 at the Feliciano Miguel Abdala Reserve, in Minas Gerais, south-eastern Brazil. We collected 49 faecal samples (scats from cats, and identified the species of cat from 23 of them by the analysis of the microstructure patterns of hairs found in their faeces: 17 scats of the puma (Puma concolor and six of the ocelot (Leopardus pardalis. In the puma scats, we identified three species of primates (Brachyteles hypoxanthus, Alouatta guariba and Sapajus nigritus, the remains of which were found in eight of 17 collected (47.1%, representing 26.7% of items consumed. For the ocelot, we detected capuchin monkey (S. nigritus remains in three of the six scats (50%, accounting for 18.7% of items consumed by ocelot. We were unable to identify the cat species in the remaining 26 faecal samples, but we were able to analyse the food items present. Primates were found in five of these 26 faeces (19.2% and represented 10.2% of the items found. Although the sample size is limited, our results indicate a relatively high consumption of primates by felines. We believe that this high predation may be the result of the high local density of primates as well as the greater exposure to the risks of predation in fragmented landscapes, which tends to increase the incidence of the primates using the ground.

NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.

Science.gov (United States)

Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

2004-03-01

The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.

Three pathogens in sympatric populations of pumas, bobcats, and domestic cats: Implications for infections disease transmission

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Bevins, Sarah N.; Carver, Scott; Boydston, Erin E.; Lyren, Lisa M.; Alldredge, Mat; Logan, Kenneth A.; Riley, Seth P.D.; Fisher, Robert N.; Vickers, T. Winston; Boyce, Walter; Salman, Mo; Lappin, Michael R.; Crooks, Kevin R.; VandeWoude, Sue

2012-01-01

Anthropogenic landscape change can lead to increased opportunities for pathogen transmission between domestic and non-domestic animals. Pumas, bobcats, and domestic cats are sympatric in many areas of North America and share many of the same pathogens, some of which are zoonotic. We analyzed bobcat, puma, and feral domestic cat samples collected from targeted geographic areas. We examined exposure to three pathogens that are taxonomically diverse (bacterial, protozoal, viral), that incorporate multiple transmission strategies (vector-borne, environmental exposure/ingestion, and direct contact), and that vary in species-specificity. Bartonella spp., Feline Immunodeficiency Virus (FIV), and Toxoplasma gondii IgG were detected in all three species with mean respective prevalence as follows: puma 16%, 41% and 75%; bobcat 31%, 22% and 43%; domestic cat 45%, 10% and 1%. Bartonella spp. were highly prevalent among domestic cats in Southern California compared to other cohort groups. Feline Immunodeficiency Virus exposure was primarily associated with species and age, and was not influenced by geographic location. Pumas were more likely to be infected with FIV than bobcats, with domestic cats having the lowest infection rate. Toxoplasma gondii seroprevalence was high in both pumas and bobcats across all sites; in contrast, few domestic cats were seropositive, despite the fact that feral, free ranging domestic cats were targeted in this study. Interestingly, a directly transmitted species-specific disease (FIV) was not associated with geographic location, while exposure to indirectly transmitted diseases – vector-borne for Bartonella spp. and ingestion of oocysts via infected prey or environmental exposure for T. gondii – varied significantly by site. Pathogens transmitted by direct contact may be more dependent upon individual behaviors and intra-specific encounters. Future studies will integrate host density, as well as landscape features, to better

Plutonium and minor actinides management in thermal high - temperature reactors - the EU FP6 project puma

International Nuclear Information System (INIS)

Kuijper, J. C.

2007-01-01

The High Temperature gas-cooled Reactor (HTR) can fulfil a very useful niche for the purposes of Pu and Minor Actinide (MA) incineration due to its unique and unsurpassed safety features, as well as to the attractive incentives offered by the nature of the coated particle (CP) fuel. No European reactor of this type is currently available, but there has been, and still is, considerable interest internationally. Decisions to construct such a reactor in China and in South Africa have already been made or are about to be made. Apart from the unique and unsurpassed safety features offered by this reactor type, the nature of the CP fuel offers a number of attractive characteristics. In particular, it can withstand burn-ups far beyond that in either LWR or FR systems. Demonstrations as high as 75% FIMA have been achieved. The coated particle itself offers significantly improved proliferation resistance, and finally with a correct choice of the kernel composition, it can be a very effective support for direct geological disposal of the fuel. The overall objective of the PUMA project, a Specific Targeted Research Project (STREP) within the European Union 6th Framework (EU FP6), is to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO 2 -free energy generation. A number of important issues concerning the use of Pu and MA in gas-cooled reactors have already been dealt with in other projects, or are being treated in ongoing projects, e.g. as part of EU FP6. However, further steps are required to demonstrate the potential of HTRs as Pu/MA transmuters based on realistic/feasible designs of CP Pu/MA fuel and the PUMA focuses on necessary

Maximal killing of lymphoma cells by DNA damage–inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim

OpenAIRE

Happo, Lina; Cragg, Mark S.; Phipson, Belinda; Haga, Jon M.; Jansen, Elisa S.; Herold, Marco J.; Dewson, Grant; Michalak, Ewa M.; Vandenberg, Cassandra J.; Smyth, Gordon K.; Strasser, Andreas; Cory, Suzanne; Scott, Clare L.

2010-01-01

DNA-damaging chemotherapy is the backbone of cancer treatment, although it is not clear how such treatments kill tumor cells. In nontransformed lymphoid cells, the combined loss of 2 proapoptotic p53 target genes, Puma and Noxa, induces as much resistance to DNA damage as loss of p53 itself. In Eμ-Myc lymphomas, however, lack of both Puma and Noxa resulted in no greater drug resistance than lack of Puma alone. A third B-cell lymphoma-2 homology domain (BH)3-only gene, Bim, although not a dire...

Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis.

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Huafei Zou

Full Text Available Caveolin-1, the structural protein component of caveolae, acts as a scaffolding protein that functionally regulates signaling molecules. We show that knockdown of caveolin-1 protein expression enhances chemotherapeutic drug-induced apoptosis and inhibits long-term survival of colon cancer cells. In vitro studies demonstrate that caveolin-1 is a novel Ku70-binding protein, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101 to the caveolin-binding domain (CBD of Ku70 (amino acids 471-478. Cell culture data show that caveolin-1 binds Ku70 after treatment with chemotherapeutic drugs. Mechanistically, we found that binding of caveolin-1 to Ku70 inhibits the chemotherapeutic drug-induced release of Bax from Ku70, activation of Bax, translocation of Bax to mitochondria and apoptosis. Potentiation of apoptosis by knockdown of caveolin-1 protein expression is greatly reduced in the absence of Bax expression. Finally, we found that overexpression of wild type Ku70, but not a mutant form of Ku70 that cannot bind to caveolin-1 (Ku70 Φ→A, limits the chemotherapeutic drug-induced Ku70/Bax dissociation and apoptosis. Thus, caveolin-1 acts as an anti-apoptotic protein in colon cancer cells by binding to Ku70 and inhibiting Bax-dependent cell death.

Tempo enhances heat-induced apoptosis by mitochondrial targeting of Bax

International Nuclear Information System (INIS)

Zhao, Q.-L.; Fujiwara, Y.; Kondo, T.

2003-01-01

A stable membrane-permeable nitroxide, Tempo, exerts an SOD-like antioxidant activity against ROS. Reportedly, Tempo inhibits ROS-induced thymocyte apoptosis, while 10 mM Tempo activates JNK1 to induce apoptosis in breast cancer cells. We have observed that nontoxic 5 mM Tempo enhances suboptimal hyperthermia (44 deg C/10 min)-induced apoptosis in U937 cells. Here we report the enhancing mechanism, focusing on activation and targeting of Bax to mitochondria and cytochrome c release. Methods: U937 cells were treated with either Tempo (5 mM, 37 deg C/10 min), heating (44 deg C/10 min), or Tempo-plus-heating, washed and incubated for various times up to 6 h, until assessing apoptosis, mitochondrial potential (ΔΨ>), and amount of superoxide by flow cytometry using Annexin V-FITC/PI, TMRM, and dihydroethidium, respectively. Bax, Bcl-2 and Bcl-XL, and cytochrome c were detected by western blotting, activated Bax was by immunoprecipitation, and ATP was by a luciferase assay. Bax targeting to and cytochrome c release from mitochorndria were also detected immunocytochemically under fluorescent microscopy. Results and Discussion: Treatment of U937 cells with 5 mM Tempo for 10 min at 37 deg C or suboptimal heating (44 deg C/ 10 min) alone did not induce apoptosis. The combined treatment with 5 mM Tempo and 44 deg C for 10 min dramatically induced ∼90% apoptosis in 6 h, as did the 44 deg C/30 min heating. During the enhanced apoptosis, cytochrome c release progressed. Although signals of Bcl-2, Bcl-XL and Bax in cell lysates were not altered, Bax was specifically activated and translocated to mitochondria after the combined treatment. Further, loss of ΔΨ>and decreases in superoxide and ATP progressed after the combined treatment, suggesting that the treatment may disturb mitochondrial electron transport. Thus, Tempo sensitizes the heat-induced apoptosis through (1) targeting of Bax to mitochondria and releasing cytochrome c, and (2) mitochondrial dysfunction

Sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC-05.

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Zhou, Lan; Yao, Qian; Li, Yan; Huang, Yun-Chao; Jiang, Hua; Wang, Chuan-Qiong; Fan, Lei

2017-01-01

Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non-smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL-05) to explore the value of sulforaphane in lung cancer prevention and treatment. Cell growth inhibition was determined by methyl thiazolyl tetrazolium assay; cell morphology and apoptosis were observed under transmission electron microscope; cell cycle and apoptosis rates were detected using flow cytometry; B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) messenger RNA expression were determined by quantitative PCR; and p53, p73, p53 upregulated modulator of apoptosis (PUMA), Bax, Bcl-2, and caspase-9 protein expression were detected by Western blotting. Sulforaphane inhibited XWLC-05 cell growth with inhibitory concentration (IC) 50 of 4.04, 3.38, and 3.02 μg/mL at 24, 48, and 72 hours, respectively. Sulforaphane affected the XWLC-05 cell cycle as cells accumulated in the G2/M phase. The proportion of apoptotic cells observed was 27.6%. Compared with the control, the sulforaphane group showed decreased Bcl-2 and p53 expression, and significantly increased p73, PUMA, Bax, and caspase-9 protein expression (P cell apoptosis. Its possible mechanism may involve the upregulation of p73 expression and its effector target genes PUMA and Bax in lung cancer cells, downregulation of the anti-apoptotic gene B cl -2, and activation of caspase-9. It may also involve downregulation of the mutant p53 protein. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating BAX expression.

Science.gov (United States)

Wang, Weicheng; Guo, Wenjie; Li, Lele; Fu, Zan; Liu, Wen; Gao, Jian; Shu, Yongqian; Xu, Qiang; Sun, Yang; Gu, Yanhong

2016-12-01

5-FU is the first line therapy for colorectal cancer, however, treatment effect is often hampered by the development of drug resistance or toxicity at high doses. Andrographolide is a natural diterpenoid from Andrographis paniculata which has anti-bacterial, anti-antiviral and anti-inflammation activities. In the current study, we test the hypothesis that Andrographolide reverses 5-FU resistance in colorectal cancer and examine the underlying mechanism. In vitro and vivo studies indicated that Andrographolide treatment significantly re-sensitizes HCT116/5-FUR cells (HCT116 cells which are 5-FU resistant) to cytotoxicity of 5-FU. Mechanism analysis showed that Andrographolide/5-FU co-treatment elevated apoptosis level of HCT116/5-FUR cells with highly increased level of BAX. By using biotin-Andrographolide pull down and cellular thermal shift assay, we found out that Andrographolide can directly target to BAX. Andrographolide-BAX interaction prevented BAX degradation, enhancing mitochondria-mediated apoptosis thus reversed 5-FU resistance while BAX silence diminished this effect. Further, by analyzing patient samples who received 5-FU involved chemotherapy, we found that expression level of BAX is correlated with PFS. Our results here provide a novel combination treatment strategy, especially for patients with 5-FU-resistant tumors expressing low level of BAX. Meanwhile, we also proposed that BAX expression may be a predicted and prognosis marker of 5-FU involved chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantifying export production in the Southern Ocean: Implications for the Baxs proxy

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Hernandez-Sanchez, Maria T.; Mills, Rachel A.; Planquette, HéLèNe; Pancost, Richard D.; Hepburn, Laura; Salter, Ian; Fitzgeorge-Balfour, Tania

2011-12-01

The water column and sedimentary Baxs distribution around the Crozet Plateau is used to decipher the controls and timing of barite formation and to evaluate how export production signals are recorded in sediments underlying a region of natural Fe fertilization within the Fe limited Southern Ocean. Export production estimated from preserved, vertical sedimentary Baxs accumulation rates are compared with published export fluxes assessed from an integrated study of the biological carbon pump to determine the validity of Baxs as a quantitative proxy under different Fe supply conditions typical of the Southern Ocean. Detailed assessment of the geochemical partitioning of Ba in sediments and the lithogenic end-member allows appropriate correction of the bulk Ba content and determination of the Baxs content of sediments and suspended particles. The upper water column distribution of Baxs is extremely heterogeneous spatially and temporally. Organic carbon/Baxs ratios in deep traps from the Fe fertilized region are similar to other oceanic settings allowing quantification of the inferred carbon export based on established algorithms. There appears to be some decoupling of POC and Ba export in the Fe limited region south of the Plateau. The export production across the Crozet Plateau inferred from the Baxs sedimentary proxy indicates that the Fe fertilized area to the north of the Plateau experiences enhanced export relative to equivalent Southern Ocean settings throughout the Holocene and that this influence may also have impacted the site to the south for significant periods. This interpretation is corroborated by alternative productivity proxies (opal accumulation, 231Paxs/230Thxs). Baxs can be used to quantify export production in complex settings such as naturally Fe-fertilized (volcanoclastic) areas, providing appropriate lithogenic correction is undertaken, and sediment focusing is corrected for along with evaluation of barite preservation.

The effect of radiation on bcl-2 and bax in hyperplastic prostatic tissues

International Nuclear Information System (INIS)

Ma Qingjie; Li Yuxin; Gu Xinquan; Cao Xia; Zhao Jie; Kong Xiangbo; Cai Shanyu

2004-01-01

Aim: To investigate the expressions of bcl-2 and bax in benign prostatic hyperplasia (BPH) and the effect of β-rays on bcl-2 and bax. Methods: The expressions of bcl-2 and bax are studied by means of immunohistochemical method in 9 normal prostate (NP) and 15 BPH and 35 patients treated with 90Sr/90Y Prostatic Hyperplasia Applicator. Results: The expressions of bcl-2 in epithelia of NP and BPH are higher than that in stroma P<0.01=. The expressions of bcl-2 in epithelia and stroma of BPH are higher than that in NP P<0.01=. The expressions of bax in epithelia of NP are higher than that in BPH P<0.05=. However ,the expressions of bcl-2 in epithelia and stroma of BPH are higher than bax P<0.01 =. Compared with the control group, the expressions of bcl-2 in epithelia and stroma of BPH treated with 90Sr/90Y Prostatic Hyperplasia Applicator decreased and the expressions of bax increased P<0.01=. Conclusion: bcl-2 gene and bax gene play an important role in the regulation of prostatic apoptosis and the treatment of β-rays can accelerate the apoptosis of prostatic tissues. (authors)

Identification of Bax-Interacting Proteins in Oligodendrocyte Progenitors during Glutamate Excitotoxicity and Perinatal Hypoxia–Ischemia

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Sopio Simonishvili

2013-11-01

Full Text Available OPC (oligodendrocyte progenitor cell death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis.

Impact of Burnout and Psychosocial Work Characteristics on Future Long-Term Sickness Absence. Prospective Results of the Danish PUMA Study Among Human Service Workers

NARCIS (Netherlands)

Borritz, Marianne; Christensen, Karl Bang; Bultmann, Ute; Rugulies, Reiner; Lund, Thomas; Andersen, Ingelise; Villadsen, Ebbe; Diderichsen, Finn; Kristensen, Tage S.

2010-01-01

Objectives: The objective of this study was to examine if burnout and psychosocial factors predicted long-term sickness absence (>2 weeks) at work unit level. Methods: Data were collected prospectively at 82-work units in human services (PUMA cohort, PUMA: Danish acronym for Burnout, Motivation and

CAT-PUMA: CME Arrival Time Prediction Using Machine learning Algorithms

Science.gov (United States)

Liu, Jiajia; Ye, Yudong; Shen, Chenglong; Wang, Yuming; Erdélyi, Robert

2018-04-01

CAT-PUMA (CME Arrival Time Prediction Using Machine learning Algorithms) quickly and accurately predicts the arrival of Coronal Mass Ejections (CMEs) of CME arrival time. The software was trained via detailed analysis of CME features and solar wind parameters using 182 previously observed geo-effective partial-/full-halo CMEs and uses algorithms of the Support Vector Machine (SVM) to make its predictions, which can be made within minutes of providing the necessary input parameters of a CME.

Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Salomons, G. S.; Buitenhuis, C. K.; Martínez Muñoz, C.; Verwijs-Jassen, M.; Behrendt, H.; Zsiros, J.; Smets, L. A.

1998-01-01

In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies.

Expression and significance of Bax protein in model of radiation injury in mouse skin

International Nuclear Information System (INIS)

Feng Yizhong; Mo Yahong

2002-01-01

Objective: The study is to find some valuable criteria for diagnosis and treatment of radiation injury in skin. Methods: The expression of Bax protein was studied by SP immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Their relationship relating to radiation dose was also investigated. Results: The expression rates of Bax were 30%, 30%, 70%, 70% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively. There was no significant correlation between the expression of Bax and radiation groups. Conclusions: The experiment shows that radiation can increase the expression of Bax protein which might be related to poor healing in radiation skin injury

Expressão da proteína Bax no tecido mamário normal de mulheres no menacme tratadas com raloxifeno Expression of Bax protein in normal tissue of premenopausal women treated with raloxifene

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Ana Maria Furtado-Veloso

2008-04-01

Full Text Available OBJETIVO: avaliar a expressão do antígeno Bax no epitélio mamário normal de mulheres na pré-menopausa tratadas com raloxifeno. MÉTODOS: estudo randomizado duplo-cego, envolvendo 33 mulheres pré-menopáusicas com fibroadenoma. As pacientes foram divididas em dois grupos: Placebo, (n=18 e Raloxifeno 60 mg, (n=15. A medicação foi usada durante 22 dias, começando no primeiro dia do ciclo menstrual. Uma biópsia foi realizada no 23º dia do ciclo menstrual, durante a qual uma amostra do tecido mamário normal adjacente ao fibroadenoma foi coletada e submetida a estudo imuno-histoquímico utilizando o anticorpo policlonal anti-Bax para avaliar a expressão da proteína Bax. A imunorreação para a proteína Bax foi avaliada, levando-se em consideração a intensidade e a fração de células coradas, cuja combinação resultou em um escore final de 0 a 6. Os casos com escore final >3 foram classificados como positivos para proteína Bax. O teste do c2 foi usado para análise estatística dos dados (pPURPOSE: to evaluate the expression of Bax antigen in the normal mammary epithelium of premenopausal women treated with raloxifene. METHODS: a randomized double-blind study was conducted in 33 ovulatory premenopausal women with fibroadenoma. Patients were divided into two groups: Placebo, (n=18 and Raloxifene 60 mg, (n=15. The medication was used for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day of the menstrual cycle and a sample of normal breast tissue adjacent to the fibroadenoma was collected and submitted to immunohistochemical study using anti-Bax polyclonal antibody to evaluate the expression of Bax protein. Immunoreaction for Bax was evaluated taking into consideration intensity and fraction of stained cells, whose combination resulted in a final score ranging from 0 to 6. Cases with a final score >3 were classified as positive for Bax. The c2 test was used for statistical

Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling.

Science.gov (United States)

Dyugovskaya, Larissa; Polyakov, Andrey; Cohen-Kaplan, Victoria; Lavie, Peretz; Lavie, Lena

2012-10-22

inhibition decreased Mcl-1 expression. Similar to neutrophils of healthy subjects exposed to IH (0.97± 0.2), in OSA neutrophils, Bax/Mcl-1 ratio was significantly lower compared to normoxic controls (1.0±0.5 vs.1.99±0.3, p=0.015), and Bax did not co-localize with mitochondria. These findings suggest that decreased Bax/Mcl-1 balance promotes neutrophil survival in IH in-vitro as well as in OSA patients. Moreover, Bax/Mcl-1 protein function in IH and SH might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.

Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling

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Dyugovskaya Larissa

2012-10-01

the IH-induced Mcl-1 increase. In SH, only p38MAPK inhibition decreased Mcl-1 expression. Similar to neutrophils of healthy subjects exposed to IH (0.97± 0.2, in OSA neutrophils, Bax/Mcl-1 ratio was significantly lower compared to normoxic controls (1.0±0.5 vs.1.99±0.3, p=0.015, and Bax did not co-localize with mitochondria. Conclusions These findings suggest that decreased Bax/Mcl-1 balance promotes neutrophil survival in IH in-vitro as well as in OSA patients. Moreover, Bax/Mcl-1 protein function in IH and SH might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.

In-house validation study of the DuPont Qualicon BAX system Q7 instrument with the BAX system PCR Assay for Salmonella (modification of AOAC Official Method 2003.09 and AOAC Research Institute Performance-Tested Method 100201).

Science.gov (United States)

Tice, George; Andaloro, Bridget; White, H Kirk; Bolton, Lance; Wang, Siqun; Davis, Eugene; Wallace, Morgan

2009-01-01

In 2006, DuPont Qualicon introduced the BAX system Q7 instrument for use with its assays. To demonstrate the equivalence of the new and old instruments, a validation study was conducted using the BAX system PCR Assay for Salmonella, AOAC Official Method 2003.09, on three food types. The foods were simultaneously analyzed with the BAX system Q7 instrument and either the U.S. Food and Drug Administration Bacteriological Analytical Manual or the U.S. Department of Agriculture-Food Safety and Inspection Service Microbiology Laboratory Guidebook reference method for detecting Salmonella. Comparable performance between the BAX system and the reference methods was observed. Of the 75 paired samples analyzed, 39 samples were positive by both the BAX system and reference methods, and 36 samples were negative by both the BAX system and reference methods, demonstrating 100% correlation. Inclusivity and exclusivity for the BAX system Q7 instrument were also established by testing 50 Salmonella strains and 20 non-Salmonella isolates. All Salmonella strains returned positive results, and all non-Salmonella isolates returned a negative response.

Opposite role of Bax and BCL-2 in the anti-tumoral responses of the immune system

International Nuclear Information System (INIS)

Bougras, Gwenola; Cartron, Pierre-François; Gautier, Fabien; Martin, Stéphane; LeCabellec, Marité; Meflah, Khaled; Gregoire, Marc; Vallette, François M

2004-01-01

The relative role of anti apoptotic (i.e. Bcl-2) or pro-apoptotic (e.g. Bax) proteins in tumor progression is still not completely understood. The rat glioma cell line A15A5 was stably transfected with human Bcl-2 and Bax transgenes and the viability of theses cell lines was analyzed in vitro and in vivo. In vitro, the transfected cell lines (huBax A15A5 and huBcl-2 A15A5) exhibited different sensitivities toward apoptotic stimuli. huBax A15A5 cells were more sensitive and huBcl-2 A15A5 cells more resistant to apoptosis than mock-transfected A15A5 cells (pCMV A15A5). However, in vivo, in syngenic rat BDIX, these cell lines behaved differently, as no tumor growth was observed with huBax A15A5 cells while huBcl-2 A15A5 cells formed large tumors. The immune system appeared to be involved in the rejection of huBax A15A5 cells since i) huBax A15A5 cells were tumorogenic in nude mice, ii) an accumulation of CD8+ T-lymphocytes was observed at the site of injection of huBax A15A5 cells and iii) BDIX rats, which had received huBax A15A5 cells developed an immune protection against pCMV A15A5 and huBcl-2 A15A5 cells. We show that the expression of Bax and Bcl-2 controls the sensitivity of the cancer cells toward the immune system. This sensitization is most likely to be due to an increase in immune induced cell death and/or the amplification of an anti tumour immune response

Loss of anti-Bax function in Gerstmann-Sträussler-Scheinker syndrome-associated prion protein mutants.

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Julie Jodoin

2009-08-01

Full Text Available Previously, we have shown the loss of anti-Bax function in Creutzfeldt Jakob disease (CJD-associated prion protein (PrP mutants that are unable to generate cytosolic PrP (CyPrP. To determine if the anti-Bax function of PrP modulates the manifestation of prion diseases, we further investigated the anti-Bax function of eight familial Gerstmann-Sträussler-Scheinker Syndrome (GSS-associated PrP mutants. These PrP mutants contained their respective methionine ((M or valine ((V at codon 129. All of the mutants lost their ability to prevent Bax-mediated chromatin condensation or DNA fragmentation in primary human neurons. In the breast carcinoma MCF-7 cells, the F198S(V, D202N(V, P102L(V and Q217R(V retained, whereas the P102L(M, P105L(V, Y145stop(M and Q212P(M PrP mutants lost their ability to inhibit Bax-mediated condensed chromatin. The inhibition of Bax-mediated condensed chromatin depended on the ability of the mutants to generate cytosolic PrP. However, except for the P102L(V, none of the mutants significantly inhibited Bax-mediated caspase activation. These results show that the cytosolic PrP generated from the GSS mutants is not as efficient as wild type PrP in inhibiting Bax-mediated cell death. Furthermore, these results indicate that the anti-Bax function is also disrupted in GSS-associated PrP mutants and is not associated with the difference between CJD and GSS.

Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins.

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Katharine J Goodall

Full Text Available Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins.

PUMA: a puzzle piece in chloroquine’s antimelanoma activity

Science.gov (United States)

Amaravadi, Ravi K.

2013-01-01

Chloroquine can induce cell death in a subset of cancer cell lines, and some melanoma cell lines are quite susceptible. While it is well known that chloroquine impairs lysosomal function and can serve as an autophagy inhibitor, the molecular target of chloroquine and the subsequent cascade of events that leads to cell death are not fully understood. Recent evidence indicates that in melanoma cell lines, chloroquine induces apoptosis by preventing degradation of the pro-apoptotic BH3-only protein PUMA. This finding adds to the unfolding story of chloroquine’s mechanism of action as a cancer therapeutic agent. PMID:23949767

THE EXPRESSION AND CLINICAL VALUE OF APOPTOSIS CONTROL GENE Bcl-2 AND Bax IN BREAST CANCER

Institute of Scientific and Technical Information of China (English)

ZHENG Jun; YAO Zhen-xiang; ZHANG Jing

1999-01-01

Objective: To study the expression and clinical value of apoptosis control gene bcl-2 and bax in breast cancer.Methods: Protein bax and bcl-2 in 41 breast cancers obtained from operations in our hospital in 1996 were detected using ABC immunohistochemical stain assay and compared with 10 cases with normal breast tissues.Results: The positive rate of bax in normal breast tissue was 90% and in breast cancer was 59%, with a significant statistical difference between them (P＜0.05), but there was no statistical difference in bcl-2 protein expression. Among the 41 breast cancer, the group with lymph node metastasis (21 cases) had obviously low bax expression (43%) and high bcl-2 expression (76%), showing significant difference to the group without lymph node metastasis (P＜0.05).Conclusion: The antiapoptosis function of bcl-2 was stronger than bax in breast cancer. Protein bax and bcl-2 assay may be useful in understanding the biological behaviors of breast cancer.

Ethanol Influences on Bax Associations with Mitochondrial Membrane Proteins in Neonatal Rat Cerebellum

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Heaton, Marieta Barrow; Siler-Marsiglio, Kendra; Paiva, Michael; Kotler, Alexandra; Rogozinski, Jonathan; Kubovec, Stacey; Coursen, Mary; Madorsky, Vladimir

2012-01-01

These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure, and focused on interactions between pro-apoptotic Bax and proteins of the permeability transition pore (PTP), voltage-dependent anion channel (VDAC), and adenine nucleotide translocator (ANT), of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that following ethanol exposure, Bax pro-apoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least two hours post-exposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment, and found such interactions were altered by ethanol treatment, but only at two-hours post-exposure, and only in the P4, ethanol-sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax, but not by a Bax channel blocker. Therefore, we conclude that at this age, within the constraints of our experimental model, a primary mode of Bax-induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex, and not channel formation independent of PTP constituents. PMID:22767450

Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX.

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Liu, Huan; Zhou, Guizhi; Fu, Xin; Cui, Haiyan; Pu, Guangrui; Xiao, Yao; Sun, Wei; Dong, Xinhua; Zhang, Libin; Cao, Sijia; Li, Guiqin; Wu, Xiaowei; Yang, Xu

2017-11-24

Lung cancer is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel diagnostic markers and therapeutic targets. Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in initiation and progression of lung cancer. However, the role of lncRNA Taurine upregulated 1 (TUG1) in lung adenocarcinoma (LAD) progression is not well known. In this study, we determined the diagnostic value of TUG1 in LAD patients, and further uncovered the underlying functional mechanism. Our results showed that TUG1 was significantly upregulated in LAD cells and serum samples. Receiver operator characteristic (ROC) analysis suggested a relatively higher area under the curve (AUC) of TUG1 (0.756) contrast to cyfra21-1 (0.619). In addition, high TUG1 level was associated with enhanced tumor size, degree of differentiation, lymph node metastases, distant metastasis and TNM stage. Cell functional assays showed that knockdown of TUG1 suppressed LAD cell viability and promoted cell apoptosis. We then sought to reveal the underlying regulatory mechanism, and the pro-apoptotic protein BAX was then identified as the downstream target of TUG1. Gain and loss functional assays showed that inhibition of BAX reversed the induced apoptosis by TUG1 knockdown. Finally, RNA immunoprecipitation and Chromatin immunoprecipitation revealed that TUG1 suppressed BAX expression through physically interacting with EZH2. In conclusion, lncRNA TUG1 is a promising diagnostic marker for LAD patients and suppression of TUG1 levels could be a future direction to promote the prognosis of LAD patients.

NDV-induced apoptosis in absence of Bax; evidence of involvement of apoptotic proteins upstream of mitochondria

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Molouki Aidin

2012-08-01

Full Text Available Abstract Background Recently it was shown that following infection of HeLa cells with Newcastle disease virus (NDV, the matrix (M protein binds to Bax and subsequently the intrinsic pathway of apoptosis is activated. Moreover, there was very little alteration on mRNA and protein levels of Bax and Bcl-2 after infection with NDV. Finding In order to further investigate the role of members of the Bcl-2 family, Bax-knockout and wild-type HCT116 cells were infected with NDV strain AF2240. Although both cells underwent apoptosis through the activation of the intrinsic pathway and the release of cytochrome c from mitochondria, the percentage of dead Bax-knockout cells was significantly lower than wt cells (more than 10% at 48 h post-infection. In a parallel experiment, the effect of NDV on HT29 cells, that are originally Bcl-2-free, was studied. Apoptosis in HT29 cells was associated with Bax redistribution from cytoplasm to mitochondria, similar to that of HeLa and wt HCT116 cells. Conclusion Although the presence of Bax during NDV-induced apoptosis contributes to a faster cell death, it was concluded that other apoptotic protein(s upstream of mitochondria are also involved since cancer cells die whether in the presence or absence of Bax. Therefore, the classic Bax/Bcl-2 ratio may not be a major determinant in NDV-induced apoptosis.

NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

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Li, Ruizhao; Zhang, Li; Shi, Wei; Zhang, Bin; Liang, Xinling; Liu, Shuangxin; Wang, Wenjian

2013-01-01

Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca 2+ was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca 2+ ]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway, which may

NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

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Li, Ruizhao, E-mail: liruizhao1979@126.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Li, E-mail: Zhanglichangde@163.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Southern Medical University, Guangzhou, Guangdong (China); Shi, Wei, E-mail: shiwei.gd@139.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Bin, E-mail: zhangbinyes@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liang, Xinling, E-mail: xinlingliang@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liu, Shuangxin, E-mail: mplsxi@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Wang, Wenjian, E-mail: wwjph@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China)

2013-04-15

Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

The studies on thyrocyte apoptosis and expression of Bcl-2 and Bax in Hashimoto's thyroiditis

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Zhao Yaping; Wang Jialing; Fan Zhiyong; Liu Zehong; Wu HeJun; Zhou Wei; Jia Meizhai

2003-01-01

To investigate the thyrocyte apoptosis, the expression of Bcl-2, Bax and the relationship between apoptosis and the pathogenesis in Hashimoto's thyroiditis (HT), 41 HT thyroid and 10 normal thyroid specimens were selected. The level of apoptosis was detected by TUNEL methods. The expression and distribution of Bcl-2 and Bax were detected using immunohistochemical methods and analyzed by Mias99 pathological image system. Immunohistochemical staining was carried out using S-P kit. The Result showed that an increased level of apoptosis was observed in Hashimoto's glands. The apoptosis mainly distributed in thyroid follicles destruction area. This was associated with increased Bax expression. The strongly positive Bcl-2 staining was observed in the thyrocyte of intact thyroid follicles. The ratios of positive granule area and total light density of Bcl-2 to those of Bax in HT thyroid follicle area were lower than those in normal thyroid. The apoptosis of thyrocyte induced by dysregulation of Bcl-2 and Bax may be involved in the pathogeneses of HT

p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

Science.gov (United States)

Litwak, Sara A.; Loh, Kim; Stanley, William J.; Pappas, Evan G.; Wali, Jibran A.; Selck, Claudia; Strasser, Andreas; Thomas, Helen E.; Gurzov, Esteban N.

2016-01-01

BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14–17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

Consumption of an adult Puma yagouaroundi (Felidae by the snake Boa constrictor (Boidae in Central Mexico Consumo de un jaguarundi adulto Puma yagouaroundi (Felidae por la serpiente Boa constrictor (Boidae en el centro de México

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Octavio Monroy-Vilchis

2011-03-01

Full Text Available Few felids have been recorded as being preyed upon by the Boa constrictor snake (Boa constrictor. Documentation of predation on felids by reptiles is scarce, and natural predators of the adult jaguarundi (Puma yagouaroundi are poorly known. Here, we report for the first time an adult male jaguarundi being eaten by the snake Boa constrictor (of 273 cm snout-to-vent length at the Sierra Nanchititla Natural Reserve, Estado de México.Pocos depredadores han sido registrados como presas de la Boa constrictor (Boa constrictor. La depredación de felinos por reptiles es escasamente documentada y los depredadores naturales del jaguarundi (Puma yagouaroundi son pobremente conocidos. Aquí, nosotros informamos de un evento de depredación de un jaguarundi macho adulto que fue consumido por una B. constrictor (longitud hocico-cloaca: 273 cm en la Reserva Natural Sierra Nanchititla, Estado de México.

Portable University Model of the Atmosphere (PUMA)

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Fraedrich, K.; Kirk, E.; Lunkeit, F. [Hamburg Univ. (Germany). Meteorologisches Inst.

1998-10-01

The Portable University Model of the Atmosphere (PUMA) is based on the Reading multi-level spectral model SGCM (Simple Global Circulation Model) described by Hoskins and Simmons (1975) and James and Gray (1986). Originally developed as a numerical prediction model, it was changed to perform as a circulation model. For example, James and Gray (1986) studied the influence of surface friction on the circulation of a baroclinic atmosphere, James and James (1992), and James et al. (1994) investigated ultra-low-frequency variability, and Mole and James (1990) analyzed the baroclinic adjustment in the context of a zonally varying flow. Frisius et al. (1998) simulated an idealized storm track by embedding a dipole structure in a zonally symmetric forcing field and Lunkeit et al. (1998) investigated the sensitivity of GCM (General Circulation Model) scenarios by an adaption technique applicapable to SGCMs. (orig.)

Effect of polysaccharides from Angelica sinensis on Bcl-2 and Bax protein expression of irradiated liver cells

International Nuclear Information System (INIS)

Sun Yuanlin; Tang Jian; Gu Xiaohong; Li Deyuan

2009-01-01

Objective: To investigate the effect of polysaccharides from Angelica sinensis (ASP3) on Bcl-2 and Bax protein expression of irradiated liver cells from mice. Methods: Bcl-2 and Bax protein expression of liver cells in vitro exposed to 2.0 Gy rays were examined by using immunohistochemistry method. Results: The expression of apoptosis-accelerating protein Bax in the irradiation group was enhanced obviously (70.83%), while apoptosis inhibiting protein Bcl-2 tended to decline (55.60%), with the statistically significant difference (P <0.01) compared with that of the control. ASP3 pretreatment could regulate Bcl-2 and Bax protein expression of liver cells, inhibiting Bax protein expression(64.14/58.37%) and increasing Bcl-2 protein expression(59.21%/ 67.45%). The differences between the high dosage (100 mg/L of ASP3) and the irradiation group were statistically significant (P<0.05). Conclusions: ASP3 pretreatment could prohibit the apoptosis of radiation- damaged liver cells due to abnormal expression of Bcl-2 and Bax, and reduce the cell apoptosis by increasing Bcl-2/Bax protein expression so as to enhance the radiation endurance of liver cells. (authors)

Bax/Bcl-2 expression ratio in prediction of response to breast cancer radiotherapy

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Hosein Azimian

2018-03-01

Full Text Available Objective(s: Radiotherapy is one of the most effective modalities of cancer therapy, but clinical responses of individual patients varies considerably. To enhance treatment efficiency it is essential to implement an individual-based treatment. The aim of present study was to identify the mechanism of intrinsic apoptosis pathway on radiosensitivity and normal tissue complications caused by the radiotherapy. Materials and Methods: Peripheral blood mononuclear cells from ten breast cancer patients were exposed to 6MV X-rays to deliver 1 and 2 Gy. Expression levels of Bax, Bcl-2, and Bax/Bcl-2 ratio were examined by relative quantitative RT-PCR. All the patients received similar tangential irradiation of the whole breast and conventional fractionation. Skin dosimetry was done by GAFChromic EBT-3 film and clinical radiosensitivity was determined using the acute reactions to radiotherapy of the skin according to Radiation Therapy Oncology Group score. All statistical analyses were performed using GraphPad Prism, version 7.01. Results: In the in-vitro experiment, Bax and Bax/Bcl-2 ratios were significantly increased with 1 and 2 Gy doses (PP0.05 for all patients. Conclusion: Significant correlation between Bax/Bcl-2 ratio determined before radiation therapy and clinical response in the patients, can be used as a biomarker to identify radiosensitive individuals. However, further studies are required to validate radiation-induced apoptotic biomarkers.

Genetic variability of Herpailurus yagouaroundi, Puma concolor and Panthera onca (Mammalia, Felidae studied using Felis catus microsatellites

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Vanessa Roma Moreno

2006-01-01

Full Text Available We used four microsatellite loci (Fca08, Fca45, Fca77 and Fca96 from the domestic cat, Felis catus, to investigate genetic variability in specimens of Herpailurus yagouaroundi (jaguarundi, otter cat, eyra, Puma concolor (cougar, mountain lion, puma and Panthera onca (jaguar held in various Brazilian zoos. Samples of DNA from the cats were PCR amplified and then sequenced before being analyzed using the CERVUS program. Our results show a mean polymorphic information content (PIC of 0.83 for H. yagouaroundi, 0.66 for P. concolor and 0.69 for P. onca and a mean of 10.3 alleles for the Fca08 locus, 5.3 for Fca 45, 9 for Fca 77 and 14 for Fca 96. These results indicate a relatively high level of genetic diversity for the specimens studied.

The radiosensitivity of glioblastoma cell lines after hypoxia-induced Bax expression

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Chen, J.K.; Hu, L.J.; Kong, E.L.; Lamborn, K.R.; Deen, D.F.

2003-01-01

Full text: Radiation therapy is the most effective treatment after surgery for patients with malignant gliomas. However, the hypoxic cells exclusive to tumor tissue have proven resistant to both radiotherapy and many forms of chemotherapy. In order to specifically target these hypoxic cells, U-251 MG and U-87 MG human glioblastoma cells were stably transfected with constructs containing the suicide gene Bax under the regulation of nine copies of hypoxia-responsive elements (HREs). During hypoxia, the transcriptional complex hypoxia-inducible-factor 1 (HIF-1) binds to HRE and facilitates the transcription of downstream genes. Previously, hypoxia-induced Bax expression in transfected U-251 and U-87 clone cells has been shown to increase cell killing. The benefits of the gene therapy could be further expanded if Bax also acted to increase the sensitivity of these clone cells to radiation. To determine whether this was the case, parent and clone cells were irradiated with graded doses of X-rays under hypoxic conditions. These cells were then left hypoxic for varying durations of time, after which they were incubated for two weeks under aerated conditions to assay for clonogenic cell survival. After less than an hour under hypoxia, both U-251 and U-87 clone cells appeared significantly more sensitive to radiation than their respective parent cells. However, after longer amounts of time under anoxia, higher surviving fractions were found in each clone that were consistent with those of their respective parent cell line, showing that potentially lethal damage repair (PLDR) had occurred in the clone cells. Parent cells did not exhibit PLDR. Results are inconclusive at this point in time. Western blot analyses detailing the amount of Bax expression at each time point as well as further research exploring different durations of hypoxia will be necessary to reveal the nature of the correlation between Bax expression and radiosensitivity. Supported by NS-42927 and CA-85356

Differential induction of p53-mediated apoptosis in medulloblastomas and gliomas correlates with their ability to induce bax

International Nuclear Information System (INIS)

Shu, H.-K.G.; Furman, Felix; Dee, Suzanne; Israel, Mark A.

1997-01-01

Purpose/Objective: Medulloblastoma cell lines readily undergo a p53-mediated apoptosis following exposure to ionizing radiation, while glioma cell lines do not undergo significant levels of apoptosis following irradiation. This study attempts to define some of the molecular events that characterize the differential ability medulloblastomas and gliomas to undergo radiation-induced apoptosis. Materials and Methods: The medulloblastoma cell lines D283 and D341 and the glioma cell lines U87, U343 and U563 were used in this study. All five cell lines were confirmed to have a wild type p53 by their ability to induce p21 protein levels and to undergo a cell-cycle arrest in G1 following treatment with ionizing radiation. Also, 3 clonal derivatives of D283 were used. Two of the clones were derived following transfection with an expression plasmid containing a dominant negative mutant p53 (Arg175 --> His) expressed from the CMV promoter (D283/53.6 and D283/53.7), while the remaining clone was derived following transfection with that same expression plasmid without mutant p53 (D283/vec). All irradiation experiments were performed on Phillips RT-250 X-ray unit using 250 Kvp X-rays. In each case, 5 Gy of ionizing radiation was given at a dose rate of 250 cGy/minute. Apoptosis was quantitated by staining fixed cells with propidium iodide and determining the percentage of cells with subdiploid DNA content by flow cytometry. Northern blot analysis was performed using standard methods. Results: The D283 and D341 cell lines exhibited a significant induction of apoptosis when assayed 2 days following treatment with radiation while the U87, U343 and U563 cell lines displayed only minimal induction of apoptosis when assayed following treatment at that time. RNA was prepared from the different cell lines that were unirradiated, 6 hours or 24 hours post-irradiation. Northern blots were made of the total RNAs and probed for bax, bcl-2 and bcl-x mRNA. This analysis detected no significant

The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

International Nuclear Information System (INIS)

Romani, Antonello A; Soliani, Paolo; Desenzani, Silvia; Borghetti, Angelo F; Crafa, Pellegrino

2006-01-01

Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA). Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3. The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients. The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression

Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

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Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

2016-07-01

Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even

Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway.

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Liu, Tiantian; Chen, Xiaoxu; Li, Tianjiao; Li, Xueliang; Lyu, Yinghua; Fan, Xiaoteng; Zhang, Pengfei; Zeng, Wenxian

2017-10-01

Spermatogonial stem cells (SSCs) possess the capacity of self-renewal and differentiation, which are the basis of spermatogenesis. In maintenance of SSC homeostasis, intrinsic/extrinsic factors and various signaling pathways tightly control the fate of SSCs. Methyltransferase SETDB1 (Set domain, bifurcated 1) catalyzes histone H3 lysine 9 (H3K9) trimethylation and represses gene expression. SETDB1 is required for maintaining the survival of spermatogonial stem cells in mice. However, the underlying molecular mechanism remains unclear. In the present study, we found that Setdb1 regulates PTEN/AKT/FOXO1 pathway to inhibit SSC apoptosis. Co-immunoprecipitation and reporter gene assay revealed that SETDB1 interacted and coordinated with AKT to regulate FOXO1 activity and expression of the downstream target genes Bim and Puma. Among the SETDB1-bound genes, the H3K9me3 levels on the promoter regions of Bim and Pten decreased in Setdb1-KD group; in contrast, H3K9me3 status on promoters of Bax and Puma remained unchanged. Therefore, SETDB1 was responsible for regulating the transcription activity of genes in the apoptotic pathway at least in part through modulating H3K9me3. This study replenishes the research on the epigenetic regulation of SSC survival, and provides a new insight for the future study of epigenetic regulation of spermatogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

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Azimahtol Hawariah LP

2007-04-01

Full Text Available Abstract Background Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. Results Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml. The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. Conclusion Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.

WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

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Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

2011-03-04

Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

International Nuclear Information System (INIS)

Zeilstra, Jurrit; Joosten, Sander P.J.; Wensveen, Felix M.; Dessing, Mark C.; Schuetze, Denise M.; Eldering, Eric; Spaargaren, Marcel; Pals, Steven T.

2011-01-01

Research highlights: → Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. → Expression profiling of apoptosis-related genes in Apc Min/+ mice revealed the differential expression of pro-apoptotic Bok and Bax. → APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. → Blocking of β-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc Min/+ mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the

TGFBR2 and BAX mononucleotide tract mutations, microsatellite instability, and prognosis in 1072 colorectal cancers.

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Kaori Shima

Full Text Available Mononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-β, TGF-β signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer as a prognostic biomarker remains uncertain.We utilized a database of 1072 rectal and colon cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional hazards model was used to compute mortality hazard ratio (HR, adjusted for clinical, pathological and molecular features including the CpG island methylator phenotype (CIMP, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072 of all colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74% (117/159 and 30% (48/158 of MSI-high tumors, respectively. In Kaplan-Meier analysis as well as univariate and multivariate Cox regression analyses, compared to microsatellite stable (MSS/MSI-low cases, MSI-high cases were associated with superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence interval (CI, 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI-high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66; p = 0.0011].TGFBR2 or BAX mononucleotide mutations are not associated with the patient survival outcome in MSI-high colorectal cancer. Our data do not support those mutations as prognostic biomarkers (beyond MSI in colorectal carcinoma.

Persian shallot, Allium hirtifolium Boiss, induced apoptosis in human hepatocellular carcinoma cells.

Science.gov (United States)

Hosseini, Farzaneh Sadat; Falahati-Pour, Soudeh Khanamani; Hajizadeh, Mohammad Reza; Khoshdel, Alireza; Mirzaei, Mohammad Reza; Ahmadirad, Hadis; Behroozi, Reza; Jafari, Nesa; Mahmoodi, Mehdi

2017-08-01

This study investigated the potential of Persian shallot extract as an anticancer agent in HepG2 tumor cell line, an in vitro human hepatoma cancer model system. The inhibitory effect of Persian shallot on the growth of HepG2 cells was measured by MTT assay. To explore the underlying mechanism of cell growth inhibition of Persian shallot, the activity of Persian shallot in inducing apoptosis was investigated through the detection of annexin V signal by flow cytometry and expression of some apoptosis related genes such p21, p53, puma, caspase-8 family-Bcl-2 proteins like bid, bim, bcl-2 and bax were measured by real-time PCR in HepG2 cells. Persian shallot extract inhibited the growth of HepG2 cells in a dose-dependent manner. The IC 50 value (inhibiting cell growth by 50%) was 149 μg/ml. The results of real-time PCR revealed a significant up-regulation of bid, bim, caspase-8, puma, p53, p21 and bax genes and a significant downregulation of bcl-2 gene in HepG2 cells treated with Persian shallot extract significantly. Therefore, this is the first report on an increased expression of bid, bim, caspase-8, puma, p53, p21 and bax genes and down regulation of bcl-2 gene indicating that the Persian shallot extract possibly induced the process of cell death through the intrinsic and extrinsic apoptosis pathways and triggers the programmed cell death in HepG2 tumor cell lines by modulating the expression of pro-/anti-apoptotic genes. Furthermore, we showed that Persian shallot extract increased annexin V signal and expression, resulting in apoptotic cell death of HepG2 cells after 24 h treatment. Therefore, according to the results of this study, the Persian shallot extract could be considered as a potential candidate for production of drug for the prevention or treatment of human hepatoma.

Correlation of mammographical imaging signs with the expression of bcl-2 and bax proteins in breast cancer

International Nuclear Information System (INIS)

Zhang Yili; Du Hongwen; Zhang Yun; Zhang Yuelang; Kuang Fangjun; Guo Zuomin

2004-01-01

Objective: To discuss the correlation of mammographical imaging signs with the expression of bcl-2 and bax proteins in breast cancer for early diagnosis and forecast of its prognoses. Methods: Fifty-four breast cancers and 26 benign diseases were proved by pathologic methods and all cases underwent mammography. Immunohistochemical technique was used to measure the expression of bcl-2 and bax proteins in these tissues. The correlation of imaging signs with the expression of bcl-2 and bax proteins in breast cancer and benign lesion was analyzed. Results: The expression of bcl-2 or bax protein in the breast cancer was higher than that in breast benign diseases (χ 2 =15.116, 11.361, P 2 =10.358, 12.818, P 2 =10.996, 10.667, P 2 =10.405, P 2 =6.841, P<0.05). Conclusion: Some imaging signs of breast cancer were closely related to the expression of bcl-2 and bax proteins and these signs could reflect the biological behavior of tumor cells and prognoses. Therefore it could be helpful to the early diagnosis and treatment of breast cancer. (authors)

Possible use of measurements to amend cross section tables (PUMA)

International Nuclear Information System (INIS)

Kherani, N.P.; Bonalumi, R.A.

1983-01-01

In a companion paper, the RAM flux mapping procedure has been demonstrated. RAM combines theory and in-core detector flux measurements, thereby recognizing a difference between the two. Assuming that the RAM ''smoothed-out'' flux distribution is exact, then the discrepancy with purely theoretical fluxes is due to inadequacies in the diffusion theory, homogenised core parameters. PUMA has been devised with the purpose of inferring adjustments in the homogenised core parameters from the theory vs. experiment flux discrepancy. This has been achieved by introducing influence functions similar to those defined by Buckler. A thorough mathematical analysis shows that influence functions are not all linearly independent and that it is crucial to use the criticality equation in the equation set. Numerical examples are shown to demonstrate the procedure

Bax and Bak Do Not Exhibit Functional Redundancy in Mediating Radiation-Induced Endothelial Apoptosis in the Intestinal Mucosa

International Nuclear Information System (INIS)

Rotolo, Jimmy A.; Maj, Jerzy G.; Feldman, Regina; Ren, Decheng; Haimovitz-Friedman, Adriana; Cordon-Cardo, Carlos; Cheng, Emily H.-Y.; Kolesnick, Richard; Fuks, Zvi

2008-01-01

Purpose: To address in vivo the issue of whether Bax and Bak are functionally redundant in signaling apoptosis, capable of substituting for each other. Methods and Materials: Mice were exposed to whole-body radiation, and endothelial cell apoptosis was quantified using double immunostaining with TUNEL and anti-CD31 antibody. Crypt survival was determined at 3.5 days after whole-body radiation by the microcolony survival assay. Actuarial animal survival was calculated by the product-limit Kaplan-Meier method, and autopsies were performed to establish cause of death. Results: Radiation exposure of Bax- and Bak-deficient mice, both expressing a wild-type acid sphingomyelinase (ASMase) phenotype, indicated that Bax and Bak are both mandatory, though mutually independent, for the intestinal endothelial apoptotic response. However, neither affected epithelial apoptosis at crypt positions 4-5, indicating specificity toward endothelium. Furthermore, Bax deficiency and Bak deficiency each individually mimicked ASMase deficiency in inhibiting crypt lethality in the microcolony assay and in rescuing mice from the lethal gastrointestinal syndrome. Conclusions: The data indicate that Bax and Bak have nonredundant functional roles in the apoptotic response of the irradiated intestinal endothelium. The observation that Bax deficiency and Bak deficiency also protect crypts in the microcolony assay provides strong evidence that the microvascular apoptotic component is germane to the mechanism of radiation-induced damage to mouse intestines, regulating reproductive cell death of crypt stem cell clonogens

Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease

Science.gov (United States)

Mason, Kylie D.; Lin, Ann; Robb, Lorraine; Josefsson, Emma C.; Henley, Katya J.; Gray, Daniel H. D.; Kile, Benjamin T.; Roberts, Andrew W.; Strasser, Andreas; Huang, David C. S.; Waring, Paul; O’Reilly, Lorraine A.

2013-01-01

Dysregulation of the “intrinsic” apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak−/−bax−/− mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doubly deficient hematopoietic compartment develop a fatal systemic lupus erythematosus-like autoimmune disease characterized by hypergammaglobulinemia, autoantibodies, lymphadenopathy, glomerulonephritis, and vasculitis. Importantly, these mice also develop a multiorgan autoimmune disease with autoantibodies against most solid glandular structures and evidence of glandular atrophy and necrotizing vasculitis. Interestingly, similar albeit less severe pathology was observed in mice containing a hematopoietic compartment deficient for only Bak, a phenotype reminiscent of the disease seen in patients with point mutations in BAK. These studies demonstrate a critical role for Bak and an ancillary role for Bax in safeguarding immunological tolerance and prevention of autoimmune disease. This suggests that direct activators of the intrinsic apoptotic pathway, such as BH3 mimetics, may be useful for treatment of diverse autoimmune diseases. PMID:23349374

Impact of burnout and psychosocial work characteristics on future long-term sickness absence. Prospective results of the Danish PUMA-study among human service workers

DEFF Research Database (Denmark)

Borritz, Marianne; Christensen, KB; Bültmann, Ute

2010-01-01

and Job satisfaction) followed up during the proceeding 18 months regarding onset of long-term sickness absence. Questionnaire data regarding burnout and psychosocial factors were aggregated at work unit level. We used Poisson regression models with psychosocial factors and burnout as predictors of long...... work environment, and equally important, the organizations should be attentive to employees with symptoms of burnout......Objectives: The objective of this study was to examine if burnout and psychosocial factors predicted long-term sickness absence (>2 weeks) at work unit level. Methods: Data were collected prospectively at 82-work units in human services (PUMA cohort, PUMA: Danish acronym for Burnout, Motivation...

Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

International Nuclear Information System (INIS)

Khor, L.-Y.; De Silvio, Michelle; Li, Rile; McDonnell, Timothy J.; Hammond, M. Elizabeth H.; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul; Sandler, Howard M.; Pollack, Alan

2006-01-01

Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer

Estradiol increases the Bax/Bcl-2 ratio and induces apoptosis in the anterior pituitary gland.

Science.gov (United States)

Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

2009-01-01

Estrogens are recognized as acting as modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals, thus participating in anterior pituitary homeostasis during the estrous cycle. The balance of pro- and antiapoptotic proteins of the Bcl-2 family is known to regulate cell survival and apoptosis. In order to understand the mechanisms underlying apoptosis during the estrous cycle, we evaluated the expression of the proapoptotic protein Bax and the antiapoptotic proteins Bcl-2 and Bcl-xL in the anterior pituitary gland in cycling female rats as well as the influence of estradiol on the expression of these proteins in anterior pituitary cells of ovariectomized rats. As determined by Western blot, the expression of Bax was higher in anterior pituitary glands from rats at proestrus than at diestrus I, Bcl-2 protein levels showed no difference and Bcl-xL expression was lower, thus increasing the Bax/Bcl-2 ratio at proestrus. Assessed by annexin V binding and flow cytometry, the percentage of apoptotic anterior pituitary cells was higher in rats at proestrus than at diestrus I. Chronic estrogen treatment in ovariectomized rats enhanced the Bax/Bcl-2 ratio and induced apoptosis. Moreover, incubation of cultured anterior pituitary cells from ovariectomized rats with 17beta-estradiol for 24 h increased the Bax/Bcl-2 ratio, decreased Bcl-xL expression and induced apoptosis. Our results demonstrate that estradiol increases the ratio between proapoptotic and antiapoptotic proteins of the Bcl-2 family. This effect could participate in the sensitizing action of estrogens to proapoptotic stimuli and therefore be involved in the high apoptotic rate observed at proestrus in the anterior pituitary gland.

Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP. Alteration of this signal in Mdx mice is a likely cause of dystrophy.

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Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

2013-01-01

ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies.

p53-Dependent radiation-induced apoptosis in vivo: relationship to Bcl-2 and Bax expression

International Nuclear Information System (INIS)

Hasegawa, Masatoshi; Suzuki, Yoshiyuki; Furuta, Masaya; Yamakawa, Michitaka; Maebayashi, Katsuya; Hayakawa, Kayoko; Saito, Yoshihiro; Mitsuhashi, Norio; Niibe, Hideo

1997-01-01

Purpose: A close correlation between p53 protein expression and radiation-induced apoptosis has already been reported, however, Bcl-2 and Bax expression and the ratio of Bcl-2 to Bax have been also suggested to play an important role in the regulation of apoptotic cell death. In this study, we investigated the relationship between p53-dependent radiation-induced apoptosis and expression of Bcl-2 and Bax by using human tumors transplanted into nude mice. Materials and Methods: Three human tumors (an ependymoblastoma, a glioblastoma, and a small cell lung cancer) were subcutaneously transplanted into nude mice and irradiated with single doses of 1, 2, 5, or 10 Gy. The tumors were excised 1, 3, 6, 12, 24, and 48 hours after irradiation, fixed in 10% formalin for 24 hours, and embedded in paraffin. Slides were stained with hematoxylin and eosin for morphologic examination. Immunohistochemical studies were performed with mouse monoclonal antibodies to demonstrate p53, p21 (WAF-1), Bcl-2, and Bax expression. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and electron microscopic studies were performed to identify apoptosis, and PCR-SSCP analysis was used to evaluate p53 gene mutation. Results: All of the tumors showed only a few cells undergoing apoptosis before irradiation. Beginning several hours after irradiation, only the ependymoblastoma showed a large increase in the number of cells undergoing apoptosis, peaking at 6 hours after irradiation, and there was a clear dose-effect relationship. In contrast, the other tumors showed much less change following irradiation, and the dose-effect relationship was not as clear as in the ependymoblastoma. Immunohistochemically, the non-irradiated ependymoblastoma was negative for p53, p21, Bcl-2, and Bax. Following irradiation, however, many of the tumor cells became positive for p53 and p21, and a few cells became positive for bcl-2. In contrast, the glioblastoma and the small cell lung cancer were positive for p53 and Bcl-2

Puma (Herpailurus) pumoides (Castellanos, 1958) nov. comb: Comentarios sistemáticos y registro fósil

OpenAIRE

Chimento, Nicolás R; Derguy, Maria Rosa; Hemmer, Helmut

2014-01-01

Entre los Felinae de procedencia dudosa descritos para Argentina se encuentra Felis pumoides Castellanos 1958, hallado en estratos asignados al Plioceno ("horizonte Brocherense”) de la provincia de Córdoba (Argentina). Los restos craneanos y post-craneanos que posee el ejemplar tipo (MUFyCA 767) fueron comparados primeramente con todos los felinos sudamericanos y con Acinonyx jubatus concluyendo que posee un gran parecido a la especie actual Puma (Herpailurus) yagouaroundi, con algunos rasgos...

Modification of the BAX System PCR assay for detecting Salmonella in beef, produce, and soy protein isolate. Performance Tested Method 100201.

Science.gov (United States)

Peng, Linda X; Wallace, Morgan; Andaloro, Bridget; Fallon, Dawn; Fleck, Lois; Delduco, Dan; Tice, George

2011-01-01

The BAX System PCR assay for Salmonella detection in foods was previously validated as AOAC Research Institute (RI) Performance Tested Method (PTM) 100201. New studies were conducted on beef and produce using the same media and protocol currently approved for the BAX System PCR assay for E. coli O157:H7 multiplex (MP). Additionally, soy protein isolate was tested for matrix extension using the U.S. Food and Drug Administration-Bacteriological Analytical Manual (FDA-BAM) enrichment protocols. The studies compared the BAX System method to the U.S. Department of Agriculture culture method for detecting Salmonella in beef and the FDA-BAM culture method for detecting Salmonella in produce and soy protein isolate. Method comparison studies on low-level inoculates showed that the BAX System assay for Salmonella performed as well as or better than the reference method for detecting Salmonella in beef and produce in 8-24 h enrichment when the BAX System E. coli O157:H7 MP media was used, and soy protein isolate in 20 h enrichment with lactose broth followed by 3 h regrowth in brain heart infusion broth. An inclusivity panel of 104 Salmonella strains with diverse serotypes was tested by the BAX System using the proprietary BAX System media and returned all positive results. Ruggedness factors involved in the enrichment phase were also evaluated by testing outside the specified parameters, and none of the factors examined affected the performance of the assay.

14-3-3theta protects against neurotoxicity in a cellular Parkinson's disease model through inhibition of the apoptotic factor Bax.

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Sunny R Slone

Full Text Available Disruption of 14-3-3 function by alpha-synuclein has been implicated in Parkinson's disease. As 14-3-3s are important regulators of cell death pathways, disruption of 14-3-3s could result in the release of pro-apoptotic factors, such as Bax. We have previously shown that overexpression of 14-3-3θ reduces cell loss in response to rotenone and MPP(+ in dopaminergic cell culture and reduces cell loss in transgenic C. elegans that overexpress alpha-synuclein. In this study, we investigate the mechanism for 14-3-3θ's neuroprotection against rotenone toxicity. While 14-3-3s can inhibit many pro-apoptotic factors, we demonstrate that inhibition of one factor in particular, Bax, is important to 14-3-3s' protection against rotenone toxicity in dopaminergic cells. We found that 14-3-3θ overexpression reduced Bax activation and downstream signaling events, including cytochrome C release and caspase 3 activation. Pharmacological inhibition or shRNA knockdown of Bax provided protection against rotenone, comparable to 14-3-3θ's neuroprotective effects. A 14-3-3θ mutant incapable of binding Bax failed to protect against rotenone. These data suggest that 14-3-3θ's neuroprotective effects against rotenone are at least partially mediated by Bax inhibition and point to a potential therapeutic role of 14-3-3s in Parkinson's disease.

Glycogen synthase kinase-3β facilitates cell apoptosis induced by high fluence low-power laser irradiation through acceleration of Bax translocation

Science.gov (United States)

Huang, Lei; Wu, Shengnan; Xing, Da

2011-03-01

Glycogen synthase kinase-3β (GSK-3β) is a critical activator of cell apoptosis induced by a diverse array of insults. However, the effects of GSK-3β on the human lung adenocarcinoma cell (ASTC-a-1) apoptosis induced by high fluence low-power laser irradiation (HF-LPLI) are not clear. Here, we showed that GSK-3β was constantly translocated from cytoplasm to nucleus and activated during HF-LPLI-induced cell apoptosis. In addition, we found that co-overexpression of YFP-GSK-3β and CFP-Bax in ASTC-a-1 cells accelerated both Bax translocations to mitochondria and cell apoptosis, compared to the cells expressed CFP-Bax only under HF-LPLI treatment, indicating that GSK-3β facilitated ASTC-a-1 cells apoptosis through acceleration mitochondrial translocation of Bax. Our results demonstrate that GSK-3β exerts some of its pro-apoptotic effects in ASTC-a-1 cells by regulating the mitochondrial localization of Bax, a key component of the intrinsic apoptotic cascade.

Distribution of 99Tcm-rh-Annexin vin tumor and expression relationship of bcl-2, bax after a single dose of chemotherapy

International Nuclear Information System (INIS)

Zhang Xin; Li Yaming; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Ji Xiaopeng; Zhao Ming; Tian Aijuan; Zhang Jianying; Zhao Zhenzhen

2007-01-01

The expression of bcl-2 and bax after the single dose of chemotherapy with 99 Tc m -rh-Annexin V as the tracer of tumor apoptosis imaging is studied. tumor cell apoptosis is examined by TUNEL methods, and the expression of bcl-2 and bax in tumor are determined by immunohistochemical methods. Single dose of chemotherapy significantly increased the tumor uptake of 99 Tc m -rh-annexin V and the positive number of TUNEL, as well as the expression of bax (P 99 Tc m -rh-annexin V in tumor reflectes not only the degree of apoptosis of tumor cells, but also the change of bax expression after the single dose of chemotherapy. (authors)

Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

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W. Y. Liu

2013-01-01

Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

PUMA Development through a Multi physics Approach

International Nuclear Information System (INIS)

Cheon, Jinsik; Kim, Junehyung; Lee, Byoungoon; Lee, Chanbock

2013-01-01

Meanwhile advances of numerical methods make it possible for the multi physics problem to be solved in a fully coupled way. In addition to a multidimensional, multi physical approach, a nuclear fuel performance analysis code, which is 1D code, should be improved by accommodating the state-of-the-art in the numerical analysis to support current fuel design and performance analysis. In particular, the coupling between the mechanical equilibrium equation and a set of numerically stiff kinetics equations for fission gas release is of great importance for a multi physics simulation of nuclear fuel. Instead, coupling between temperature and fuel constituent was found to be made with a relative ease by employing an ordinary differential equations solver. As an effort for a new SFR metal fuel performance analysis code, called PUMA (Performance of Uranium Metal fuel rod Analysis code), the deformation of U-Zr fuel for SFR in connection with a fission gas release model is analyzed. A finite element analyses for purely mechanical problems are performed using a backward differentiation formula, and are subjected to scrupulous verification with Abaqus. Then mechanical equilibrium equation and the equations for fission gas release are coupled with the same differential-algebraic equations (DAE) solver

Contesting the Equivalency of Continuous Sedation until Death and Physician-assisted Suicide/Euthanasia: A Commentary on LiPuma.

Science.gov (United States)

Raho, Joseph A; Miccinesi, Guido

2015-10-01

Patients who are imminently dying sometimes experience symptoms refractory to traditional palliative interventions, and in rare cases, continuous sedation is offered. Samuel H. LiPuma, in a recent article in this Journal, argues that continuous sedation until death is equivalent to physician-assisted suicide/euthanasia based on a higher brain neocortical definition of death. We contest his position that continuous sedation involves killing and offer four objections to the equivalency thesis. First, sedation practices are proportional in a way that physician-assisted suicide/euthanasia is not. Second, continuous sedation may not entirely abolish consciousness. Third, LiPuma's particular version of higher brain neocortical death relies on an implausibly weak construal of irreversibility--a position that is especially problematic in the case of continuous sedation. Finally, we explain why continuous sedation until death is not functionally equivalent to neocortical death and, hence, physician-assisted suicide/euthanasia. Concluding remarks review the differences between these two end-of-life practices. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

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Yoon TH

2012-03-01

Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

Sensitivity of landscape resistance estimates based on point selection functions to scale and behavioral state: Pumas as a case study

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Katherine A. Zeller; Kevin McGarigal; Paul Beier; Samuel A. Cushman; T. Winston Vickers; Walter M. Boyce

2014-01-01

Estimating landscape resistance to animal movement is the foundation for connectivity modeling, and resource selection functions based on point data are commonly used to empirically estimate resistance. In this study, we used GPS data points acquired at 5-min intervals from radiocollared pumas in southern California to model context-dependent point selection...

The Impact of Adenosine Fast Induction of Myocardial Arrest during CABG on Myocardial Expression of Apoptosis-Regulating Genes Bax and Bcl-2

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Ahmed Shalaby

2009-01-01

Full Text Available Background. We studied the effect of fast induction of cardiac arrest with denosine on myocardial bax and bcl-2 expression. Methods and Results. 40 elective CABG patients were allocated into two groups. The adenosine group (n=20 received 250 μg/kg adenosine into the aortic root followed by blood potassium cardioplegia. The control group received potassium cardioplegia in blood. Bcl-2 and bax were measured. Bax was reduced in the postoperative biopsies (1.38 versus 0.47, P=.002 in the control group. Bcl-2 showed a reducing tendency (0.14 versus 0.085, P=.07. After the adenosine treatment, the expression of both bax (0.52 versus 0.59, P=.4 and bcl-2 (0.104 versus 0.107, P=.4 remained unaltered after the operation. Conclusion. Open heart surgery is associated with rapid reduction in the expression of apoptosis regulating genes bax and bcl-2. Fast Adenosine induction abolished changes in their expression.

Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates.

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Stidl, R; Fuchs, S; Bossard, M; Siekmann, J; Turecek, P L; Putz, M

2016-01-01

BAX 855 is a PEGylated human full-length recombinant factor VIII (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has been optimized to retain functionality of the FVIII molecule, improve its pharmacokinetic properties and allow less frequent injections while maintaining efficacy. The aim of this study was to confirm that the excellent safety profile of ADVATE remains unchanged after PEGylation. Non-clinical safety studies with BAX 855 and its respective unbound polyethylene glycol (PEG) were conducted in several species. The distribution of a single dose of radiolabelled BAX 855 was further investigated in rats. Publically available safety data on PEG alone and PEGylated biomolecules were summarized and reviewed for specific safety findings attributable to PEG or PEGylated biopharmaceuticals. Safety pharmacology studies in rabbits and macaques and repeated dose toxicity studies in rats and macaques identified no safety issues. Results of a distribution study in rats administered radiolabelled BAX 855 showed that radioactivity was completely excreted; urine was the major elimination route. A 28-day study in rats dosed with the unbound PEG constituent (PEG2ru20KCOOH) of BAX 855 showed no adverse or non-adverse effects. Safety data for PEG and PEG-protein conjugates indicate no safety concerns associated with PEG at clinically relevant dose levels. Although vacuolation of certain cell types has been reported in mammals, no such vacuolation was observed with BAX 855 or with the unbound PEG constituent. Non-clinical safety evaluation of PEG and BAX 855 identified no safety signals; the compound is now in clinical development for the treatment of patients with haemophilia A. © 2015 Baxalta Innovations GmbH. Haemophilia Published by John Wiley & Sons Ltd.

Apoptosis, proliferation, Bax, Bcl-2 and p53 status prior to and after preoperative radiochemotherapy for locally advanced rectal cancer

International Nuclear Information System (INIS)

Tannapfel, Andrea; Nuesslein, Siegfried; Fietkau, Rainer; Katalinic, Alexander; Koeckerling, Ferdinand; Wittekind, Christian

1998-01-01

Purpose: To investigate the relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis regulating proteins in rectal cancer prior to and after radiochemotherapy. Materials and Methods: In 32 patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma, pretherapy biopsies and the final resected specimen after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The expression of the bax protein was assessed immunohistochemically. Additionally, double immunostaining was performed for apoptotic cells and bax expression. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2 expression was analyzed immunohistochemically. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%). During follow-up, tumor recurrence was observed in six cases. In one case, no residual tumor was detected after radiochemotherapy. Results: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased in resected specimens as compared to biopsies. Bax immunostaining was detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the resected specimen, significantly more apoptotic cells that were bax-positive were found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31 resected specimens, respectively. Tumors that were immunohistochemically negative for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high expression level of bax than p53-positive tumors (11/31 [35%]). However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis or the level of bax expression and the degree of

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

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Jenson, Justin M.; Ryan, Jeremy A.; Grant, Robert A.; Letai, Anthony; Keating, Amy E. (DFCI); (MIT)

2017-06-08

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.

Startup transient simulation for natural circulation boiling water reactors in PUMA facility

International Nuclear Information System (INIS)

Kuran, S.; Xu, Y.; Sun, X.; Cheng, L.; Yoon, H.J.; Revankar, S.T.; Ishii, M.; Wang, W.

2006-01-01

In view of the importance of instabilities that may occur at low-pressure and -flow conditions during the startup of natural circulation boiling water reactors, startup simulation experiments were performed in the Purdue University Multi-Dimensional Integral Test Assembly (PUMA) facility. The simulations used pressure scaling and followed the startup procedure of a typical natural circulation boiling water reactor. Two simulation experiments were performed for the reactor dome pressures ranging from 55 kPa to 1 MPa, where the instabilities may occur. The experimental results show the signature of condensation-induced oscillations during the single-phase-to-two-phase natural circulation transition. The results also suggest that a rational startup procedure is needed to overcome the startup instabilities in natural circulation boiling water reactor designs

Parámetros genético poblacionales en seis especies de Felidae neotropicales ( Leopardus tigrina, L. wiedii, L. pardalis, Herpailurus jagouroundi, Puma concolor y Pantera onca

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M. Ruiz-García

2001-07-01

Full Text Available Se analizaron 196 muestras pertenecientes a 68 Leopardus pardalis (Ocelote; Colombia, Perú, a12 L. wiedi (Margay; Colombia y Bolivia, a 24 L. tigrinus (Tigrillo; Colombia, a 16 Herpailurus jagouroundi (yagouroundi; Colombia, Venezuela, Brasil a 50 Puma concolor (Puma; Colombia, Perú, Bolivia y a 24 Panthera onca (Jaguar; Colombia con 6 marcadores microsatélites diferentes (FCA08, FCA43, FCA45, FCA90, FCA96 y FCA126. Los resultados y conclusiones más obvias fueron las siguientes: (1 Para la mayoría de esas especies no se dio equilibrio Hardy- Weinberg cuando se analizaron individuos de localidades diferentes por exceso de homocigotos. Probablemente, el efecto Wahlund es responsable de ese hecho.

Attitudes toward jaguars and pumas and the acceptability of killing big cats in the Brazilian Atlantic Forest: An application of the Potential for Conflict Index2.

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Engel, Monica T; Vaske, Jerry J; Bath, Alistair J; Marchini, Silvio

2017-09-01

We explored the overall acceptability of killing jaguars and pumas in different scenarios of people-big cat interactions, the influence of attitudes toward big cats on acceptability, and the level of consensus on the responses. Data were obtained from 326 self-administered questionnaires in areas adjacent to Intervales State Park and Alto Ribeira State Park. Overall, people held slightly positive attitudes toward jaguars and pumas and viewed the killing of big cats as unacceptable. However, individuals that held negative attitudes were more accepting of killing. As the severity of people-big cat interactions increased, the level of consensus decreased. Knowing whether killing a big cat is acceptable or unacceptable in specific situations allows managers to anticipate conflict and avoid illegal killing of big cats.

Response to LiPuma and DeMarco’s Article on “Hastening Death”

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Julia Zenz

2017-05-01

Full Text Available The paper “Palliative care and patient autonomy: moving beyond prohibitions against hastening death” by LiPuma and DeMarco deals with an aspect of end of life care which is the source of considerable disagreement. It is important to emphasize that autonomy is not the unique feature for end of life care. There is always a medical and ethical commitment to care, i.e. beneficence and nonmaleficence. All of these aspects have to be taken into account when treating patients at the very end of life. There is considerable scientific proof indicating that most patients and families can experience a death in dignity when being cared for in palliative care or hospice units.

Novel type of neutron polarization analysis using the multianalyzer-equipment of the three-axes spectrometer PUMA

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Schwesig, Steffen; Maity, Avishek; Sobolev, Oleg; Ziegler, Fabian; Eckold, Götz

2018-01-01

The combination of polarization analysis and multianalyzer system available at the three axes spectrometer PUMA@FRM II allows the simultaneous determination of both spin states of the scattered neutrons and the absolute value of the polarization. The present paper describes the technical details along with the basic formalism used for the precise calibration. Moreover, the performance of this method is illustrated by several test experiments including first polarized inelastic studies of the magnetic excitations of CuO in the multiferroic and the uniaxial antiferromagnetic phases.

Apoptosis and Bax expression are increased by coal dust in the polycyclic aromatic hydrocarbon-exposed lung

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Ghanem, M.M.; Battelli, L.A.; Mercer, R.R.; Scabilloni, J.F.; Kashon, M.L.; Ma, J.Y.C.; Nath, J.; Hubbs, A.F.

2006-09-15

Miners inhaling respirable coal dust (CD) frequently develop coal workers' pneumoconiosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette smoke, which may contribute to lung disease in these workers. Recently, apoptosis was reported to play a critical role in the development of another pneumoconiosis of miners, silicosis. In addition, CID was reported to suppress cytochrome P450 1A1 (CYP1A1) induction by PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal P-naphthoflavone (BNF), a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan-caspase inhibitor Q-VD-OPH (quinoline-Val-Asp (OMe)-CH{sub 2}-OPH). In rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan-caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition. It is concluded that combined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.

Coenzyme Q10 Protects Hippocampal Neurons Against Ischemia/Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

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M Zamani

2012-12-01

Full Text Available Introduction : Preliminary studies confirmed reduction in cell death following treatment with antioxidants. According to this finding we study the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis.Material & methods : We studied the protective role of CoQ10 against Ischemia-Reperfusion. Experimental design includes four groups: intact, ischemic control, sham control and treatment groups with CoQ10. The mice treated with CoQ10 as Pre - Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation (a week the mice post-treated with CoQ10.Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression.Results :. Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups.Conclusion : Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and prevented the expression of bax while inducing an increase in expression of bcl2.

Expanded polyglutamine embedded in the endoplasmic reticulum causes membrane distortion and coincides with Bax insertion

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Ueda, Masashi; Li, Shimo; Itoh, Masanori; Wang, Miao-xing; Hayakawa, Miki; Islam, Saiful; Tana; Nakagawa, Kiyomi [Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Chen, Huayue [Department of Anatomy, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Nakagawa, Toshiyuki, E-mail: tnakagaw@gifu-u.ac.jp [Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

2016-05-27

The endoplasmic reticulum (ER) is important in various cellular functions, such as secretary and membrane protein biosynthesis, lipid synthesis, and calcium storage. ER stress, including membrane distortion, is associated with many diseases such as Huntington's disease. In particular, nuclear envelope distortion is related to neuronal cell death associated with polyglutamine. However, the mechanism by which polyglutamine causes ER membrane distortion remains unclear. We used electron microscopy, fluorescence protease protection assay, and alkaline treatment to analyze the localization of polyglutamine in cells. We characterized polyglutamine embedded in the ER membrane and noted an effect on morphology, including the dilation of ER luminal space and elongation of ER-mitochondria contact sites, in addition to the distortion of the nuclear envelope. The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. These results demonstrated that the ER membrane may be a target of polyglutamine, which triggers cell death through Bax. -- Highlights: •We characterized polyglutamine embedded in the ER membrane. •The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. •The ER membrane may be a target of polyglutamine, which triggers cell death.

The effect of N-nitrosodimethylamine (NDMA) on Bax and Mcl-1 expression in human neutrophils.

Science.gov (United States)

Jablonski, Jakub; Jablonska, Ewa; Leonik, Agnieszka

2011-12-01

In the present study we examined a role of pro-apoptotic Bax and anti-apoptotic Mcl-1 proteins, participating in the regulation of intrinsic apoptosis pathway in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA), the environmental xenobiotic. For the purpose comparison, the same studies were conducted in autologous peripheral blood mononuclear cells (PBMCs). The production of cytochrome c by PMNs was also determined. A deficit of anti-apoptotic Mcl-1 and overexpression of the pro-apoptotic protein Bax suggest that the apoptosis process in human neutrophils exposed to NDMA is dependent on changes in the expression of these proteins. PMNs were more sensitive to NDMA than PBMCs.

Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in patients with chronic gastritis and gastric cancer.

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Bartchewsky, Waldemar; Martini, Mariana R; Squassoni, Aline C; Alvarez, Marisa C; Ladeira, Marcelo S P; Salvatore, Daisy M F; Trevisan, Miriam A; Pedrazzoli, José; Ribeiro, Marcelo L

2010-01-01

The aim of the present study is to evaluate the influence of Helicobacter pylori on Bax and Bcl-2 mRNA and protein levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected; 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by PCR, and the expression values were determined by quantitative real-time PCR and immunohistochemistry. Our data showed that the up-regulationary effects of H. pylori infection on the pro-apoptotic gene, Bax, were stronger than its induction of Bcl-2; this effect may increase apoptosis in patients with chronic gastritis. In patients with gastric cancer, the up-regulation of the anti-apoptotic gene, Bcl-2, counteracted the pro-apoptotic effects of Bax, leading to a deregulation of apoptosis-associated gene expression, favoring cell proliferation. Thus, the disturbance in Bax and Bcl-2 balance, induced by H. pylori, might be important in gastric cancer development.

Coenzyme Q10 Protects Hippocampal Neurons against Ischemia/ Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

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Mohammad Zamani

2012-09-01

Full Text Available Introduction: Preliminary studies have con.rmed reduction in cell death following treatment with antioxidants. According to this .nding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. Methods: We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups:  intact, ischemic control, sham control and treatment group with CoQ10. The mice were pre-treated with CoQ10 for a week, then ischemia was induced by common carotid artery ligation and following the reduction in in.ammation (a week the mice was treated with CoQ10.  Nissl staining was applied for counting the necrotic cells of hippocampus and the western blot was performed to measure the Bax and Bcl2 expression.Results: Cell death was signi.cantly lower when mice were treated with CoQ10. Bax expression was signi.cantly high in the ischemic group but low in the treatment group, and the bcl2 expression was lower in the ischemic group than the treatment and the vehicle groups.Discussion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake signi.cantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2.

Simulasi Penggunaan Ipv6 Pada PD. Pumas Jaya Menggunakan Metode Manual Tunneling

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Elidjen Elidjen

2010-12-01

Full Text Available Internet usage trends with IPv4 addresses that only have 32-bit addresses could no longer cope with the large allocation of the required addresses. Internet Engineering Task Force (IETF has issued a new standard of Internet protocol called IPv6 to anticipate this problem. PD. Pumas Jaya, which started in 1996 in the field of marine products in particular marinated seafood, such as salted fish, rebon shrimp, cuttlefish, anchovies and other marine products to anticipate the need for this in its network. However, IPv6 can not simply be used to replace IPv4 as the existing network infrastructure with IPv4. This research discussed IPv6 simulation tunneling with manual methods so that an IPv6 site can communicate with other IPv6 site even if separated by an infrastructure that supports only IPv4. 

Borax-induced apoptosis in HepG2 cells involves p53, Bcl-2, and Bax.

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Wei, Y; Yuan, F J; Zhou, W B; Wu, L; Chen, L; Wang, J J; Zhang, Y S

2016-06-21

Borax, a boron compound and a salt of boric acid, is known to inhibit the growth of tumor cells. HepG2 cells have been shown to be clearly susceptible to the anti-proliferative effects of borax. However, the specific mechanisms regulating this effect are poorly understood. This study aimed to investigate the pathways underlying the growth inhibition induced by borax in HepG2 cells. The effects of borax on HepG2 cell viability were characterized using MTT. Apoptosis was also verified by annexin V/propidium iodide staining. JC-1 dye and western blotting techniques were used to measure mitochondrial membrane potential and p53, Bax, and Bcl-2 protein expression, respectively. Relevant mRNA levels were measured by qRT-PCR. Borax inhibited the proliferation of HepG2 cells in a time- and dose-dependent manner in vitro. The apoptotic process triggered by borax involved the upregulation of p53 and Bax and the downregulation of Bcl-2, which was confirmed by a change in the mitochondrial membrane potential. These results elucidate a borax-induced apoptotic pathway in HepG2 cells that involves the upregulation of p53 and Bax and the downregulation of Bcl-2.

Reconstitution of the anti-apoptotic Bcl-2 protein into lipid membranes and biophysical evidence for its detergent-driven association with the pro-apoptotic Bax protein.

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Marcus Wallgren

Full Text Available The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2 protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax, are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23-lauryl-ether (Brij-35 detergent at a level below its critical micelle concentration (CMC. Additional surface plasmon resonance (SPR measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A2 (a known inhibitory ligand of Bcl-2 to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC. Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.

[Effects of blueberry on apoptosis and expression of Bcl-2 and Bax in HSC-T6].

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Lu, Shuang; Cheng, Mingliang; Yang, Demeng; Liu, Yang; Guan, Li; Wu, Jun

2015-08-18

To investigate the effects of blueberry on the apoptosis, expression of Bcl-2 and Bax in rat hepatic stellate cell (HSC-T6). 10% blueberry serum at low, middle and high dose, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum were prepared by method of serum pharmacology. Subcultured HSC-T6 was divided into saline serum control group, blueberry serum at low, middle, high dose and Fu-Fang-Bie-Jia-Ruan-Gan tablet serum group, and then was respectively incubated at different dose of 10% blueberry serum, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum for 72 hours.Apoptosis of HSC-T6 was detected using flow cytometry with annexin V FITC/PI double staining. The expression of Bcl-2 and Bax in HSC-T6 were examined using immunocytochemistry and Western blotting, respectively. There was no significant difference for HSC-T6 Bax protein expression in the low, middle and high dose blueberry serum groups, compared with saline serum control group, respectively.In the high-dose blueberry serum group HSC-T6 early and total apoptosis rate increased significantly compared with the saline serum control group (5.55% ± 0.98% vs 2.53% ± 0.46%, 7.01% ± 1.05% vs 2.96% ± 0.81%, both Pblueberry serum group showed no significant difference with the saline serum control group. Blueberry can induce HSC-T6 apoptosis by down-regulating Bcl-2 expression and decreasing the ratio of Bcl-2/Bax in HSC-T6 cells, so it may have potential interference effects on hepatic fibrosis.

The BH3 α-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner*

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Kazi, Aslamuzzaman; Sun, Jiazhi; Doi, Kenichiro; Sung, Shen-Shu; Takahashi, Yoshinori; Yin, Hang; Rodriguez, Johanna M.; Becerril, Jorge; Berndt, Norbert; Hamilton, Andrew D.; Wang, Hong-Gang; Sebti, Saïd M.

2011-01-01

A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-XL, and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-XL and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-XL, Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-XL/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-XL, Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612. PMID:21148306

Preparation and Photocatalytic Properties of Sr2−xBaxTa3O10−yNz Nanosheets

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Tatsumi Ishihara

2013-01-01

Full Text Available Sr2−xBaxTa3O10−yNz (x = 0.0, 0.5, 1.0 nanosheets were prepared by exfoliating layered perovskite compounds (CsSr2−xBaxTa3O10−yNz. The Sr1.5Ba0.5Ta3O9.7N0.2 nanosheet showed the highest photocatalytic activity for H2 production from the water/methanol system among the Sr2−xBaxTa3O9.7N0.2 nanosheets prepared. In addition, Rh-loaded Sr1.5Ba0.5Ta3O9.6N0.3 nanosheet showed the photocatalytic activity for oxygen and hydrogen production from water. The ratio of hydrogen to oxygen evolved was around two. These results indicate that the Rh-loaded Sr1.5Ba0.5Ta3O9.6N0.3 nanosheet is a potential catalyst for photocatalytic water splitting.

Forward Models for Following a Moving Target with the Puma 560 Robot Manipulator

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Daniel Fernando Tello Gamarra

2015-12-01

Full Text Available This paper describes how a forward model could be applied in a manipulator robot to accomplish the task of following a moving target. The forward model has been implemented in the puma 560 robot manipulator in simulation after a babbling motor phase using ANFIS neural networks. The forward model delivers a rough estimation of the position in the operational space of a moving target. Using this information a Cartesian controller tracks the moving target. An implementation of the proposed architecture and the Piepmeir algorithm for the problem of following a moving target is also shown in the paper. The control architecture proposed in this paper was also tested with MLP and RBF neural networks. Results and simulations are shown to demonstrate the applicability of our proposed architecture for tracking a moving target.

Paclitaxel-induced apoptosis is BAK-dependent, but BAX and BIM-independent in breast tumor.

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Anna V Miller

Full Text Available Paclitaxel (Taxol-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim(-/- MEFs (mouse embryonic fibroblasts, the bim(-/- mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak (-/- MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax(-/- MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance.

The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation

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Fang Chen

2016-04-01

Full Text Available Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O, has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu and Cat D inhibitor (pepA inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05 in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome.

Mode of cell death induced by the HSP90 inhibitor 17-AAG (tanespimycin) is dependent on the expression of pro-apoptotic BAX.

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Powers, Marissa V; Valenti, Melanie; Miranda, Susana; Maloney, Alison; Eccles, Suzanne A; Thomas, George; Clarke, Paul A; Workman, Paul

2013-11-01

Inhibitors of the molecular chaperone heat shock protein 90 (HSP90) are of considerable current interest as targeted cancer therapeutic agents because of the ability to destabilize multiple oncogenic client proteins. Despite their resulting pleiotropic effects on multiple oncogenic pathways and hallmark traits of cancer, resistance to HSP90 inhibitors is possible and their ability to induce apoptosis is less than might be expected. Using an isogenic model for BAX knockout in HCT116 human colon carcinoma cells, we demonstrate the induction of BAX-dependent apoptosis at pharmacologically relevant concentrations of the HSP90 inhibitor 17-AAG both in vitro and in tumor xenografts in vivo. Removal of BAX expression by homologous recombination reduces apoptosis in vitro and in vivo but allows a lower level of cell death via a predominantly necrotic mechanism. Despite reducing apoptosis, the loss of BAX does not alter the overall sensitivity to 17-AAG in vitro or in vivo. The results indicate that 17-AAG acts predominantly to cause a cytostatic antiproliferative effect rather than cell death and further suggest that BAX status may not alter the overall clinical response to HSP90 inhibitors. Other agents may be required in combination to enhance tumor-selective killing by these promising drugs. In addition, there are implications for the use of apoptotic endpoints in the assessment of the activity of molecularly targeted agents.

The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner.

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Kazi, Aslamuzzaman; Sun, Jiazhi; Doi, Kenichiro; Sung, Shen-Shu; Takahashi, Yoshinori; Yin, Hang; Rodriguez, Johanna M; Becerril, Jorge; Berndt, Norbert; Hamilton, Andrew D; Wang, Hong-Gang; Sebti, Saïd M

2011-03-18

A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-X(L), and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-X(L) and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-X(L), Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-X(L)/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-X(L), Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612.

Determination of stoichiometry and concentration of trace elements in thin BaxSr1-xTiO3 perovskite layers.

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Becker, J S; Boulyga, S F

2001-07-01

This paper describes an analytical procedure for determining the stoichiometry of BaxSr1-xTiO3 perovskite layers using inductively coupled plasma mass spectrometry (ICP-MS). The analytical results of mass spectrometry measurements are compared to those of X-ray fluorescence analysis (XRF). The performance and the limits of solid-state mass spectrometry analytical methods for the surface analysis of thin BaxSr1-xTiO3 perovskite layers sputtered neutral mass spectrometry (SNMS)--are investigated and discussed.

Generic Techniques for the Calibration of Robots with Application of the 3-D Fixtures and Statistical Technique on the PUMA 500 and ARID Robots

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Tawfik, Hazem

1991-01-01

A relatively simple, inexpensive, and generic technique that could be used in both laboratories and some operation site environments is introduced at the Robotics Applications and Development Laboratory (RADL) at Kennedy Space Center (KSC). In addition, this report gives a detailed explanation of the set up procedure, data collection, and analysis using this new technique that was developed at the State University of New York at Farmingdale. The technique was used to evaluate the repeatability, accuracy, and overshoot of the Unimate Industrial Robot, PUMA 500. The data were statistically analyzed to provide an insight into the performance of the systems and components of the robot. Also, the same technique was used to check the forward kinematics against the inverse kinematics of RADL's PUMA robot. Recommendations were made for RADL to use this technique for laboratory calibration of the currently existing robots such as the ASEA, high speed controller, Automated Radiator Inspection Device (ARID) etc. Also, recommendations were made to develop and establish other calibration techniques that will be more suitable for site calibration environment and robot certification.

Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

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Lyu C

2017-08-01

Full Text Available Chuang Lyu,1,2 Gong-Wei Lyu,3 Aurora Martinez,4 Tie-Jun Sten Shi4 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China; 2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; 3Department of Neurology, 1st Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Biomedicine, University of Bergen, Bergen, Norway Background: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods: A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results: There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion: Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self

Feline infectious peritonitis in a mountain lion (Puma concolor), California, USA.

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Stephenson, Nicole; Swift, Pamela; Moeller, Robert B; Worth, S Joy; Foley, Janet

2013-04-01

Feline infectious peritonitis (FIP) is a fatal immune-mediated vasculitis of felids caused by a mutant form of a common feline enteric virus, feline enteric coronavirus. The virus can attack many organ systems and causes a broad range of signs, commonly including weight loss and fever. Regardless of presentation, FIP is ultimately fatal and often presents a diagnostic challenge. In May 2010, a malnourished young adult male mountain lion (Puma concolor) from Kern County, California, USA was euthanized because of concern for public safety, and a postmortem examination was performed. Gross necropsy and histopathologic examination revealed necrotizing, multifocal myocarditis; necrotizing, neutrophilic, and histiocytic myositis and vasculitis of the tunica muscularis layer of the small and large intestines; and embolic, multifocal, interstitial pneumonia. Feline coronavirus antigen was detected in both the heart and intestinal tissue by immunohistochemistry. A PCR for coronavirus performed on kidney tissue was positive, confirming a diagnosis of FIP. Although coronavirus infection has been documented in mountain lions by serology, this is the first confirmed report of FIP.

Calculation of the CAREM reactor with the HUEMUL-PUMA-THERMIT chain of codes; Calculo del reactor CAREM con la cadena de codigos HUEMUL-PUMA-THERMIT

Energy Technology Data Exchange (ETDEWEB)

Notari, Carla; Grant, Carlos R [Comision Nacional de Energia Atomica, General San Martin (Argentina)

2000-07-01

The purpose of the work was the evaluation of the the CAREM 25 reactor core, using a chain of codes (HUEMUL-PUMA-THERMIT) different to the one used in the original design (CONDOR-CITVAP-THERMIT). First, we performed a partial validation of the our codes in lattices similar to CAREM and reproduced a benchmark for simulation of gadolinium burnup. The results were considered satisfactory for this stage of the project. Then, we calculated the core along the normal operating equilibrium cycle and in hot and cold shut-down conditions. The main outcome of our evaluation confirms the general behaviour of the reference calculations except in one important point referring to the cold shut down. In this condition, the failure of one single rod of bank number 13 of the shut down system, leaves the core in a supercritical state at the beginning of the cycle and this anomaly persists during almost a third of the overall cycle. A new design of the core is proposed with minor modifications of the reference one, without introducing new types of fuel elements and keeping the same fuel management scheme. This new core fulfills all the design requirements. (author)

Effect of Bcl-2/Bax gene expression on apoptosis of spermatogenic cells of mouse testes induced by low dose radiation

International Nuclear Information System (INIS)

Liu Guangwei; Wang Chunyan; Lu Zhe; Liu Shunchun; Gong Shouliang

2003-01-01

The different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptosis and Bcl-2 and Bax protein expression were measured with flow cytometry and immunohistochemical method, respectively. The results showed the apoptosis in all kinds of spermatogenic cells induced by low dose radiation (LDR) had a obvious regularity. When the doses were 0.025 and 0.05 Gy, spermatogonia apoptosis was dominant. With the increase of irradiation dose (0.075-0.2 Gy), spermatocytes also showed an apoptotic change, but the apoptotic percentage of spermatogonia was significantly higher than that of spermatocytes. Moreover, the apoptosis of spermatids and spermatozoa scarcely occurred after LDR. Bax protein was primarily expressed in spermatogonia and spermatocytes, and the former was significantly higher than that of the latter after LDR. With the increase of irradiation dose, Bax protein expression showed a upgrading tendency, but that of spermatids and spermatozoa scarcely occurred. Bcl-2 protein was primarily expressed in spermatids and spermatozoa, but the Bcl-2 protein expressions of spermatogonia and spermatocytes scarcely occurred after LDR. These results imply that the interacting regulation of Bcl-2 and Bax gene expression might be involved in selective apoptosis of spermatogenic cells induced by LDR, which provided an experimental evidence for further exploring the apoptotic mechanism of adaptive response of spermatogenic cells by LDR

The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma.

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Jolanta Kunert-Radek

2004-03-01

Full Text Available It is well established that disruption of apoptosis may lead to tumor initiation, progression or metastasis. It is also well documented that many anticancer drugs induce apoptosis. In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC and somatostatin analog octreotide (OCT were found to inhibit the growth of the estrogen-induced rat prolactinoma. Our previous investigations, applying the TUNEL method showed the involvement of the pro-apoptotic effect in the action of BC, and to a lesser degree, in the action of OCT. The aim of the present study was to investigate whether the pro-apoptotic action of these drugs involves the increased expression of Bax--a member of Bcl-2 protein family which is known to play an important role in the regulation of apoptosis. Male four-week Fisher 344 rats were used in the experiment. Capsules containing diethylstilboestrol (DES were implanted subcutaneously. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24, BC (3 mg/kg b.w./24 h or OCT and BC at the above doses for 10 days. Bax expression was detected by immunohistochemistry. Prolactin (PRL in blood serum was measured by radioimmunoassay (RIA. It has been found that both OCT and BC, alone or in combination, significantly reduce the tumor weight. Both OCT and BC suppressed PRL levels, but the inhibitory effect of BC was stronger than that of OCT. It has been found that the treatment with OCT and BC, alone or in combination, causes a significant increase in Bax expression in the rat prolactinoma cells. Our findings indicate that anti-tumoral action of bromocriptine and to some extent the action of octreotide in the experimental rat prolactinoma is connected with the induction of apoptosis and is associated with increased Bax expression.

"A carne mais barata do mercado é a carne negra: uma reflexão sobre o "design" das camisas da Puma na Copa do Mundo de Futebol/2010 "The cheapest flesh in the market is the black one": body, soccer and advertising Puma uniforms in the 2010 soccer world cup

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Victor Andrade de Melo

2011-06-01

Full Text Available A Puma, uma empresa de material esportivo, desde meados da primeira década do século XXI tem constantemente utilizado jogadores negros em suas campanhas publicitárias, parte de uma estratégia de busca de aproximação com o continente africano. À beira da falência no início dos anos 90, a empresa conseguiu se reposicionar no mercado unindo o esporte à moda, investindo em produtos de "design" arrojado. Uma de suas iniciativas foi buscar inspiração no "caráter exótico" das nações africanas para produzir peças que possam ser utilizadas em situações cotidianas, não só para a prática de esportes. Como o corpo do negro africano tem sido representado em suas estratégias publicitárias? Esse estudo teve por objetivo analisar um ponto específico da publicidade da Puma por ocasião da Copa do Mundo de Futebol de 2010, realizada na África do Sul: o "design" das camisas fornecidas a três seleções africanas - Camarões, Costa do Marfim e Gana. Para alcance do objetivo, entabulamos uma comparação com os modelos das camisas fornecidas pela empresa a outros selecionados (Suíça, Uruguai e Itália, prospectando o quanto suas ações publicitárias reforçam ou não certos estereótipos comumente observados quando se utilizam negros em campanhas de publicidade.Puma, a company of sport gears, has been inserting black soccer players in its advertising campaigns as a strategy to get closer to the African continent. Near to bankruptcy at the 90' beginning, the company has succeeded in bringing to the market products with more daring design, linking fashion and sports. One of its latest initiatives was to seek inspiration in the exotic profile of African people to produce pieces that can be used in all occasions not only for sports. How African's bodies have been exposed in its adverting campaigns? The objective of this study was to analyze an specific issue related to some strategies adopted in Puma advertising campaigns launched during

USP22 Induces Cisplatin Resistance in Lung Adenocarcinoma by Regulating γH2AX-Mediated DNA Damage Repair and Ku70/Bax-Mediated Apoptosis

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Aman Wang

2017-05-01

Full Text Available Resistance to platinum-based chemotherapy is one of the most important reasons for treatment failure in advanced non-small cell lung cancer, but the underlying mechanism is extremely complex and unclear. The present study aimed to investigate the correlation of ubiquitin-specific peptidase 22 (USP22 with acquired resistance to cisplatin in lung adenocarcinoma. In this study, we found that overexpression of USP22 could lead to cisplatin resistance in A549 cells. USP22 and its downstream proteins γH2AX and Sirt1 levels are upregulated in the cisplatin- resistant A549/CDDP cell line. USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A. In addition, USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax-mediated apoptosis and inducing cisplatin resistance. The cisplatin sensitivity in cisplatin-resistant A549/CDDP cells was restored by USP22 inhibition in vivo and vitro. In summary, our findings reveal the dual mechanism of USP22 involvement in cisplatin resistance that USP22 can regulate γH2AX-mediated DNA damage repair and Ku70/Bax-mediated apoptosis. USP22 is a potential target in cisplatin-resistant lung adenocarcinoma and should be considered in future therapeutic practice.

The concept of fuel cycle integrated molten salt reactor for transmuting Pu+MA from spent LWR fuels

International Nuclear Information System (INIS)

Hirose, Y.; Takashima, Y.

2001-01-01

Japan should need a new fuel cycle, not to save spent fuels indefinitely as the reusable resources but to consume plutonium and miner actinides orderly without conventional reprocessing. The key component is a molten salt reactor fueled with the Pu+MA (PMA) separated from LWR spent fuels using fluoride volatility method. A double-tiered once-through reactor system can burn PMA down to 5% remnant ratio, and can make PMA virtually free from the HAW to be disposed geometrically. A key issue to be demonstrated is the first of all solubility behavior of trifluoride species in the molten fuel salt of 7 LiF-BeF 2 mixture. (author)

Photobiomodulation on Bax and Bcl-2 Proteins and SIRT1/PGC-1α Axis mRNA Expression Levels of Aging Rat Skeletal Muscle

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Fang-Hui Li

2014-01-01

Full Text Available Objective. This study aimed to analyze the effects of low level laser irradiation (LLLI on Bax and IGF-1 and Bcl-2 protein contents and SIRT1/PGC-1α axis mRNA expression levels to prevent sarcopenia in aged rats. Material and Methods. Twenty female Sprague Dawley rats (18 months old were randomly divided into two groups (n=10 per group: control (CON and LLLI groups. The gallium-aluminum-arsenium (GaAlAs laser irradiation at 810 nm was used in the single point contact mode (3.75 J/cm2; 0.4 cm2; 125 mW/cm2; 30 s. Bax, Bcl-2, and IGF-1 proteins and SIRT1/PGC-1α axis mRNA expression were assessed 24 h after LLLI on gastrocnemius in aged rat. Results. Gastrocnemius muscle weights, gastrocnemius mass/body mass, Bcl-2/BAX ratio, Bcl-2 protein, IGF-1 protein, and the mRNA contents in SIRT1, PGC-1α, NRF1, TMF, and SOD2 were significantly (P<0.05 increased by LLLI compared to CON group without LLLI. However, levels of BAX protein and caspase 3 mRNA were significantly attenuated by LLLI compared to CON group (P<0.05. Conclusion. LLLI at 810 nm inhibits sarcopenia associated with upregulation of Bcl-2/BAX ratio and IGF-1 and SIRT1/PGC-1α axis mRNA expression in aged rats. This indicates that LLLI has potential to decrease progression of myocyte apoptosis in sarcopenic muscles.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A.

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Siu, Woen Ping; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A

2008-03-15

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (>500 microM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 microM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca2+-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

International Nuclear Information System (INIS)

Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A.

2008-01-01

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 μM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 μM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca 2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca 2+ -Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury

Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer

International Nuclear Information System (INIS)

Sun, Yue; Du, Chengli; Wang, Bo; Zhang, Yanling; Liu, Xiaoyan; Ren, Guoping

2014-01-01

Highlights: • The expression of eEF1A2 is up-regulated in prostate cancer tissues. • Suppression of eEF1A2 inhibits the proliferation and promotes apoptosis. • Inhibition of eEF1A2 enhances the expression of apoptotic relevant proteins. • The expressions of eEF1A2 and cleavage-caspase3 are inversely correlated. - Abstract: Background: eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. Methods: We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Results: Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Conclusion: Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer

An Assay of Bax and Bcl2 Expression in Mice Hippocampus Following Ischemia-Reperfusion Treatment with CoQ10

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Jalal Hassanshahi

2013-10-01

Full Text Available Introduction: Preliminary studies confirmed reduction of cell death following treatment with antioxidants. According to this finding we investigated the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus ischemia that this expression related to cell programmed death.Material and Methods: We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups: intact (N=7, ischemic control (N=7, sham control (N=7 and treatment groups with CoQ10 (N=7. The mice (treatment group treated with CoQ10 as Pre-Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation (a week the treatment group post-treated with CoQ10 for a week. Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply Y-maze.Results: Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups. The memory test results were consistent with cell death results. Conclusion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and decreased memory loss. with prevent of expression of bax and increase in expression of bcl2.

Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability

International Nuclear Information System (INIS)

Yashiro, Masakazu; Hirakawa, Kosei; Boland, C Richard

2010-01-01

Microsatellite instability (MSI) occurs in 15% of colorectal cancers (CRC). The genetic targets for mutation in the MSI phenotype include somatic mutations in the transforming growth factor beta receptor typeII (TGFbetaRII), BAX, hMSH3 and hMSH6. It is not clear how mutations of these genes mediate tumor progression in the MSI pathway, and the temporal sequence of these mutations remains uncertain. In this study, early stage CRCs were examined for frameshift mutations in these target genes, and compared with late stage tumors and CRC cell lines. We investigated 6 CRC cell lines and 71 sporadic CRCs, including 61 early stage cancers and 10 late stage cancers. Mutations of repetitive mononucleotide tracts in the coding regions of TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR and Fas antigen were identified by direct sequencing. Thirteen (18.3%) of 71 CRC, including 9/61 (14.7%) early stage cancers and 4/10 (40%) late stage cancers, were identified as MSI and analyzed for frameshift mutations. No mutation in the target genes was observed in any of the 9 early stage MSI CRCs. In contrast, frameshift mutations of TGFbetaRII, BAX, hMSH3 and hMSH6 were present in 3/4 late stage MSI tumors. There is a statistical association (p = 0.014) between mutation in any one gene and tumor stage. TGFbetaRII, BAX, hMSH3 and hMSH6 mutations are relatively late events in the genesis of MSI CRCs. The frameshift mutations in these target genes might mediate progression from early to late stage cancer, rather than mediating the adenoma to carcinoma transition

Differential Effects of Ethanol on c-Jun N-Terminal Kinase, 14-3-3 Proteins, and Bax in Postnatal Day 4 and Postnatal Day 7 Rat Cerebellum

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Heaton, Marieta Barrow; Paiva, Michael; Kubovic, Stacey; Kotler, Alexandra; Rogozinski, Jonathan; Swanson, Eric; Madorsky, Vladimir; Posados, Michelle

2011-01-01

These studies investigated ethanol effects on upstream cellular elements and interactions which contribute to Bax-related apoptosis in neonatal rat cerebellum at ages of peak ethanol sensitivity (postnatal day 4 [P4]), compared to later ages of relative resistance (P7). Analyses were made of basal levels of the pro-apoptotic c-jun N-termimal kinase (JNK), Bax, and the 14-3-3 anchoring proteins, as well as the responsiveness of these substances to ethanol at P4 versus P7. Dimerization of Bax with 14-3-3 was also investigated at the two ages following ethanol treatment, a process which sequesters Bax in the cytosol, thus inhibiting its mitochondrial translocation and disruption of the mitochondrial membrane potential. Cultured cerebellar granule cells were used to examine the protective potential of JNK inhibition on ethanol-mediated cell death. Basal levels of JNK were significantly higher at P4 than P7, but no differences in the other proteins were found. Activated JNK, and cytosolic and mitochondrially-translocated Bax were increased in P4 but not P7 animals following ethanol exposure, while protective 14-3-3 proteins were increased only at P7. Ethanol treatment resulted in decreases in Bax:14-3-3 heterodimers at P4, but not at P7. Inhibition of JNK activity in vitro provided partial protection against ethanol neurotoxicity. Thus, differential temporal vulnerability to ethanol in this CNS region correlates with differences in both levels of apoptosis-related substances (e.g., JNK), and differential cellular responsiveness, favoring apoptosis at the most sensitive age and survival at the resistant age. The upstream elements contributing to this vulnerability can be targets for future therapeutic strategies. PMID:22169498

Interacciones hiperfinas en BaxSr1-xHfO3

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López García, A.

1999-10-01

Full Text Available In order to determine the microscopic role of cation A in ABO3 perovskites the hyperfine interaction in the Sr1-xBaxHfO3 system using Perturbed Angular Correlation spectroscopy (PAC is studied. As a previous result the compositions x = 0.50 and 0.25 are shown. The PAC spectra were obtained in the temperature range from 20 to 1000ºC. In both compounds a phase transition to higher symmetry structure was observed at T≈400 and 200ºC, respectively. This structure is proposed to be cubic in both compositions. The results are compared with those obtained in SrHfO3 and BaHfO3.Con el fin de determinar el papel microscópico que juega el catión A en las perovskitas ABO3 se estudia la interacción hiperfina el sistema Sr1-xBaxHfO3 usando la espectroscopia Correlaciones Angulares Perturbadas (PAC en función de la temperatura y la composición. Como resultado previo se muestra en este trabajo, el estudio de las composiciones x = 0.5 y 0.75. Las medidas PAC se realizaron en el intervalo de temperaturas que va desde 20 a 1000ºC. Para x=0.50 y 0.75 se determinó una transición a una fase de mayor simetría a T≈400 y 200ºC, respectivamente. Se propone que esta fase de mayor simetría es cúbica en ambas composiciones. Los resultados obtenidos son comparados con los compuestos puros SrHfO3 y BaHfO3.

Adsorption of xylene para- and meta- isomers in NaX and BaX zeolites. Study of properties-structure relations; Adsorption des isomeres para- et meta- du xylene dans les zeolithes NaX et BaX. Etude des relations proprietes-structure

Energy Technology Data Exchange (ETDEWEB)

Descours, A.

1997-02-14

The separation of para-xylene from C8 aromatics is performed industrially bu adsorption process on zeolitic molecular sieves. The sorption properties of these zeolites are strongly linked to their structure, and their comprehension require an accurate knowledge of the interactions between sorbate molecules and zeolitic structure. The aim of this work is to characterise from a structural point of view the adsorption of para- and meta-xylenes in BaX and NaX zeolites. The former is selective for para-xylene, and the latter has not selective properties for para- and meta-isomers of xylene. For each zeolite, the adsorption of pure para-xylene and meta-xylene or a mixture of the two isomers, is investigated as a function of coverage. Powder neutron diffraction is used to determine the crystalline structure of these zeolites and the different crystallographic adsorption sites of the molecules. The influence of coverage on sorbate-sorbent and sorbate-sorbate interactions is investigated. Infrared spectroscopy allows to determine the chemical environment of the sorbate molecules at low coverage or when the coverage increases, and is particularly effective for the study of the binary mixture of xylenes. This study is performed by sorbing a mixture of xylene isomers, or by sorbing these isomers successively. Infrared studies and crystallographic analysis are compared in order to get a consistent description of adsorption mechanism of xylene isomers for both zeolites as a function of coverage. The role of coverage, of cation type, an the presence of the two xylene isomers is the super-cages is essential. For both zeolites, the increase of coverage actually leads to steric hindrances between sorbed molecules and molecular rearrangements. These reorganizations are connected to the cationic distribution of NaX and BaX zeolites. The sorbed molecules are connected to the cationic distribution of NaX and BaX zeolites. The sorbed molecules are particularly confined in BaX zeolite

Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

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Hangjun Ruan

1999-11-01

Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.

Science.gov (United States)

Csatlós, Éva; Máté, Szabolcs; Laky, Marcella; Rigó, János; Joó, József Gábor

2015-07-01

To describe gene expression patterns of the apoptotic regulatory genes Bcl and Bax in human uterine leiomyoma tissue. To investigate the relationship between alterations of gene expression patterns and several relevant clinical parameters. We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for gene expression analysis of the Bcl-2 and Bax genes. Gene expression was quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was significantly overexpressed compared with the control group although there was no such difference in the gene expression of Bax. Gene activity of Bcl-2 positively correlated with the tumor number in individual uterine leiomyoma cases. Although there was no significant correlation between the length of the cumulative lactation period before the development of uterine leiomyoma and Bcl-2 gene expression in the leiomyoma tissue, we observed a trend for a shorter cumulative lactation period to be associated with overexpression of the Bcl-2 gene. Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax gene did not seem to play a role in the process.

Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

Science.gov (United States)

Mignani, Serge; El Brahmi, Nabil; Eloy, Laure; Poupon, Joel; Nicolas, Valérie; Steinmetz, Anke; El Kazzouli, Said; Bousmina, Mosto M; Blanchard-Desce, Mireille; Caminade, Anne-Marie; Majoral, Jean-Pierre; Cresteil, Thierry

2017-05-26

A multivalent phosphorus dendrimer 1G 3 and its corresponding Cu-complex, 1G 3 -Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G 3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Anomalous metallic state with strong charge fluctuations in BaxTi8O16 +δ revealed by hard x-ray photoemission spectroscopy

Science.gov (United States)

Dash, S.; Kajita, T.; Okawa, M.; Saitoh, T.; Ikenaga, E.; Saini, N. L.; Katsufuji, T.; Mizokawa, T.

2018-04-01

We have studied a charge-orbital driven metal-insulator transition (MIT) in hollandite-type BaxTi8O16 +δ by means of hard x-ray photoemission spectroscopy (HAXPES). The Ti 2 p HAXPES indicates strong Ti3 +/Ti4 + charge fluctuation in the metallic phase above the MIT temperature. The metallic phase is characterized by a power-law spectral function near the Fermi level which would be a signature of bad metal with non-Drude polaronic behavior. The power-law spectral shape is associated with the large Seebeck coefficient of the metallic phase in BaxTi8O16 +δ .

Genética e conservação do leão-baio (Puma concolor) no sul do Brasil

OpenAIRE

Camila Schlieper de Castilho

2010-01-01

O leão-baio (Puma concolor), segundo maior felino neotropical, tem a maior distribuição geográfica nas Américas. A subespécie que ocorre no sul do Brasil é listada como least concern e vulnerável nas listas de espécies ameaçadas da IUCN e do Ministério do Meio Ambiente brasileiro, respectivamente. Em áreas nas quais a onça-pintada (Panthera onca) foi localmente extinta, o leão-baio tem o papel de predador de topo de cadeia alimentar influenciando na manutenção de processos do ecossistema e na...

BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

Science.gov (United States)

Xu, Guogang; Vogel, Kristine S; McMahan, C Alex; Herbert, Damon C; Walter, Christi A

2010-12-01

During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

Schiff Base Metal Derivatives Enhance the Expression of HSP70 and Suppress BAX Proteins in Prevention of Acute Gastric Lesion

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Shahram Golbabapour

2013-01-01

Full Text Available Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg, the positive control (Tween 20 5% v/v, 5 mL/kg, and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg. After 1 h, all of the groups received ethanol 95% (5 mL/kg but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg. The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E, immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX proteins in prevention of acute gastric lesion.

Science.gov (United States)

Golbabapour, Shahram; Gwaram, Nura Suleiman; Al-Obaidi, Mazen M Jamil; Soleimani, A F; Ali, Hapipah Mohd; Abdul Majid, Nazia

2013-01-01

Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg), the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h, all of the groups received ethanol 95% (5 mL/kg) but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E), immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Involvement of Bax and Bcl2 in Neuroprotective Effect of Curcumin in Kainic Acid-Induced Model of Temporal Lobe Epilepsy in Male Rat

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zahra Kiasalari

2016-04-01

Full Text Available Background & objectives: Temporal lobe epilepsy is associated with neuronal apoptosis. Curcumin has antioxidant and anticonvulsant activities, therefore this study was conducted to assess involvement of Bax and Bcl2 in protective effect of curcumin in epileptic rats. Methods: 28 rats were divided into sham, curcumin-pretreated sham, epileptic (kainate, and curcumin-pretreated epileptic groups. Experimental model of epilepsy was induced by intrahippocampal administration of kainic acid. Rats received curcumin at a dose of 100 mg/kg. Finally, Nissl staining and Bax and Bcl2 immunohistochemistry were conducted on hippocampal sections and data were analyzed using one-way ANOVA and unpaired t-test. The p-value less than 0.05was considered statistically significant. Results: Induction of epilepsy was followed by a significant seizure and curcumin pretreatment significantly reduced seizure intensity (p<0.01. In addition, there were no significant differences between the groups in Nissl staining of CA3 area neurons. In addition, Bax positive neurons were observed in CA3 area in kainate group and significantly decreased in curcumin pretreated rats (p<0.05. Meanwhile, Bcl2 positive neurons were also moderately observed in kainate group and curcumin pretreatment significantly increased it (p<0.05. Conclusion: Curcumin pretreatment exhibits anticonvulsant activity in epileptic rats. It also decreases the expression of pro-apoptotic protein Bax and significantly enhances the expression of anti-apoptotic protein Bcl2 and hence could reduce neuronal apoptosis.

Synthesis and characterization of BaxMgyAl2O4: Eu,Dy nanophosphors prepared using solution-combustion method

CSIR Research Space (South Africa)

Kebede, MA

2011-07-01

Full Text Available Europium-doped barium magnesium aluminate (BaxMgyAl2O4:Eu) phosphors were obtained at low temperature using the solution-combustion of corresponding metal nitrate-urea solution mixtures. The particle sizes, morphology, structural and luminescent...

JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins

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Nomeda Girnius

2017-11-01

Full Text Available Summary: Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis. While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that JNK acts through a BAK/BAX-dependent apoptotic pathway by increasing BIM expression and phosphorylating BMF, leading to death of detached epithelial cells. : Developmental morphogenesis, tissue injury, and oncogenic transformation can cause epithelial cell detachment. These cells are eliminated by a specialized form of apoptosis termed anoikis. Girnius and Davis show that anoikis is mediated by the cJUN NH2-terminal kinase (JNK, which increases BIM expression and phosphorylates BMF to engage BAK/BAX-dependent apoptosis. Keywords: apoptosis, anoikis, epithelial cell, mammary gland, JNK, BAX, BAK, BH3-only protein, BIM, BMF

MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin.

Science.gov (United States)

Nardiello, Tricia; Jungbluth, Achim A; Mei, Anna; Diliberto, Maurizio; Huang, Xiangao; Dabrowski, Ania; Andrade, Valéria C C; Wasserstrum, Rebecca; Ely, Scott; Niesvizky, Ruben; Pearse, Roger; Coleman, Morton; Jayabalan, David S; Bhardwaj, Nina; Old, Lloyd J; Chen-Kiang, Selina; Cho, Hearn Jay

2011-07-01

The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67(+) malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells. The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis. MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms. These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms.

Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

International Nuclear Information System (INIS)

Mohseni, Mehran; Mihandoost, Ehsan; Shirazi, Alireza; Sepehrizadeh, Zargham; Bazzaz, Javad Tavakkoly; Ghazi-khansari, Mahmoud

2012-01-01

The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT 2 qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Mohseni, Mehran [Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan (Iran, Islamic Republic of); Mihandoost, Ehsan, E-mail: mihandoost.e@gmail.com [Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shirazi, Alireza [Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sepehrizadeh, Zargham [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bazzaz, Javad Tavakkoly [Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-khansari, Mahmoud [Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2012-10-15

The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT{sup 2}qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

Cycloheximide and actinomycin D delay death and affect bcl-2, bax, and Ice gene expression in astrocytes under in vitro ischemia.

Science.gov (United States)

Yu, Albert Cheung Hoi; Yung, Hon Wa; Hui, Michael Hung Kit; Lau, Lok Ting; Chen, Xiao Qian; Collins, Richard A

2003-10-15

An in vitro ischemia model was established and the effect of the metabolic inhibitors cycloheximide (CHX) and actinomycin D (ActD) on apoptosis in astrocytes under ischemia studied. CHX decreased by 75% the number of cells dying after 6 hr of ischemia compared with control cultures. TdT-mediated dUTP nick end labelling (TUNEL) staining of comparable cultures was reduced by 40%. ActD decreased cell death by 60% compared with controls. The number of TUNEL-positive cells was reduced by 38%. The nuclear shrinkage in TUNEL-positive astrocytes in control cultures did not occur in ActD-treated astrocytes, indicating that nuclear shrinkage and DNA fragmentation during apoptosis are two unrelated processes. Expression of bcl-2 (alpha and beta), bax, and Ice in astrocytes under similar ischemic conditions, as measured by quantitative reverse transcription-polymerase chain reaction, indicated that ischemia down-regulated bcl-2 (alpha and beta) and bax. Ice was initially down-regulated from 0 to 4 hr, before returning to control levels after 8 hr of ischemia. ActD decreased the expression of these genes. CHX reduced the expression of bcl-2 (alpha and beta) but increased bax and Ice expression. It is hypothesized that the balance of proapoptotic (Bad, Bax) and antiapoptotic (Bcl-2, Bcl-Xl) proteins determines apoptosis. The data suggest that the ratio of Bcl-2/Bad in astrocytes following ActD and CHX treatment does not decrease as much in untreated cells during ischemia. Our data indicate that it is the ratio of Bcl-2 family members that plays a critical role in determining ischemia-induced apoptosis. It is also important to note that ischemia-induced apoptosis involves the regulation of RNA and protein synthesis. Copyright 2003 Wiley-Liss, Inc.

Expression of Bax in yeast affects not only the mitochondria but also vacuolar integrity and intracellular protein traffic

DEFF Research Database (Denmark)

Dimitrova, Irina; Toby, Garabet G; Tili, Esmerina

2004-01-01

-transferase (BI-GST) leads to aggregation, but not fusion of the mitochondria. In addition, Bax affects the integrity of yeast vacuoles, resulting in the disintegration and eventual loss of the organelles, and the disruption of intracellular protein traffic. While Bcl-2 coexpression only partially corrects...

Calculation of the CAREM reactor with the HUEMUL-PUMA-THERMIT chain of codes

International Nuclear Information System (INIS)

Notari, Carla; Grant, Carlos R.

2000-01-01

The purpose of the work was the evaluation of the the CAREM 25 reactor core, using a chain of codes (HUEMUL-PUMA-THERMIT) different to the one used in the original design (CONDOR-CITVAP-THERMIT). First, we performed a partial validation of the our codes in lattices similar to CAREM and reproduced a benchmark for simulation of gadolinium burnup. The results were considered satisfactory for this stage of the project. Then, we calculated the core along the normal operating equilibrium cycle and in hot and cold shut-down conditions. The main outcome of our evaluation confirms the general behaviour of the reference calculations except in one important point referring to the cold shut down. In this condition, the failure of one single rod of bank number 13 of the shut down system, leaves the core in a supercritical state at the beginning of the cycle and this anomaly persists during almost a third of the overall cycle. A new design of the core is proposed with minor modifications of the reference one, without introducing new types of fuel elements and keeping the same fuel management scheme. This new core fulfills all the design requirements. (author)

Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

Science.gov (United States)

Kwon, Oh Sang; Pyo, Hyun Keol; Oh, Youn Jin; Han, Ji Hyun; Lee, Se Rah; Chung, Jin Ho; Eun, Hee Chul

2007-01-01

Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21. PMID:17449938

BaxSr1-xTi1.02O3 metal-insulator-metal capacitors on planarized alumina substrates

NARCIS (Netherlands)

Tiggelman, M.P.J.; Reimann, K.; Klee, M.; Mauczok, R.; Keur, W.; Hueting, Raymond Josephus Engelbart

2010-01-01

Nanocrystalline barium strontium titanate (BaxSr1−xTi1.02O3) thin films with a barium content of x=0.8, 0.9 and 1 have been fabricated in a metal–insulator–metal configuration on glass-planarized alumina substrates. Cost-effective processing measures have been utilized by using poly-crystalline

The multianalyser system of the three axes neutron spectrometer PUMA: Pilot experiments with the innovative multiplex technique

Energy Technology Data Exchange (ETDEWEB)

Sobolev, Oleg; Hoffmann, Ron; Gibhardt, Holger [Institute for Physical Chemistry, Georg-August-University of Göttingen, Tammannstr. 6, D-37077 Göttingen (Germany); Jünke, Norbert [Forschungs-Neutronenquelle Heinz-Maier-Leibnitz, Technical University of Munich, Lichtenbergstr. 1, D-85748 Garching (Germany); Knorr, Andreas; Meyer, Volker [Institute for Physical Chemistry, Georg-August-University of Göttingen, Tammannstr. 6, D-37077 Göttingen (Germany); Eckold, Götz, E-mail: geckold@gwdg.de [Institute for Physical Chemistry, Georg-August-University of Göttingen, Tammannstr. 6, D-37077 Göttingen (Germany)

2015-02-01

A new type of multiplex technique for three axes neutron spectrometers has been realized and successfully commissioned at the PUMA spectrometer at FRM II. Consisting of eleven analyser-detector channels which can be configured individually, this technique is especially suitable for kinetic experiments where a single excitation spectrum is recorded as a function of time without the need to move the spectrometer. On a time-scale of seconds an entire spectrum can be recorded thus allowing users to monitor changes during fast kinetic processes in single shot experiments without the need for stroboscopic techniques. Moreover, the multianalyser system provides an efficient and rapid tool for mapping excitations in (Q,ω)-space. The results of pilot experiments demonstrate the performance of this new technique and a user-friendly software is presented which assists users during their experiments.

Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin

DEFF Research Database (Denmark)

Liang, Y G; Jorgensen, A G; Kaestel, C G

2000-01-01

PURPOSE. The aim of this study was to determine the role of Bcl-2, Bcl-X L, Bax, and c-Fos in regulation of apoptosis, induced by ultraviolet-light A (UV-A) and daunorubicin (DNR), in retinal pigment epithelium (RPE) cells grown on bovine extracellular matrix (ECM)-coated or uncoated plastic dishes....... METHODS. Apoptosis in confluent RPE cells cultured on ECM-coated or uncoated dishes was induced by UV-A or DNR. Apoptosis was detected by 7-amino-actinomycin D labeling followed by flow cytometry and by terminal deoxy-transferase mediated X-dUTP nick end labeling (TUNEL). Cellular expression of Bcl-2, Bcl......-X L, Bax, and c-Fos was determined by the use of antibodies and flow cytometry, Western blot analysis, and immunocytochemical staining. RESULTS. Both UV-A and DNR induce apoptosis in human RPE cells in vitro. Human fetal RPE cells grown on ECM-coated dishes were significantly more resistant to UV...

Inhibition of Xenograft tumor growth by gold nanoparticle-DNA oligonucleotide conjugates-assisted delivery of BAX mRNA.

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Ji-Hyun Yeom

Full Text Available Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.

Ab-initio study of structural, elastic, electronic and thermodynamic properties of BaxSr1−xS ternary alloys

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Chelli S.

2015-12-01

Full Text Available The structural, elastic, electronic and thermodynamic properties of BaxSr1−xS ternary alloys have been investigated using the full-potential (linearized augmented plane wave method. The ground state properties, such as lattice constant, bulk modulus and elastic constants, are in good agreement with numerous experimental and theoretical data. The dependence of the lattice parameters, bulk modulus and band gap on the composition x was analyzed. Deviation of the lattice constant from Vegard’s law and the bulk modulus from linear concentration dependence (LCD was observed. The microscopic origins of the gap bowing were explained by using the approach of Zunger et al. The thermodynamic stability of BaxSr1−xS alloy was investigated by calculating the excess enthalpy of mixing, ΔHm and the calculated phase diagram showed a broad miscibility gap with a critical temperature.

Electromagnetic radiation at 900 MHz induces sperm apoptosis through bcl-2, bax and caspase-3 signaling pathways in rats.

Science.gov (United States)

Liu, Qi; Si, Tianlei; Xu, Xiaoyun; Liang, Fuqiang; Wang, Lufeng; Pan, Siyi

2015-08-04

The decreased reproductive capacity of men is an important factor contributing to infertility. Accumulating evidence has shown that Electromagnetic radiation potentially has negative effects on human health. However, whether radio frequency electromagnetic radiation (RF-EMR) affects the human reproductive system still requires further investigation. Therefore, The present study investigates whether RF-EMR at a frequency of 900 MHz can trigger sperm cell apoptosis and affect semen morphology, concentration, and microstructure. Twenty four rats were exposed to 900 MHz electromagnetic radiation with a special absorption rate of 0.66 ± 0.01 W/kg for 2 h/d. After 50d, the sperm count, morphology, apoptosis, reactive oxygen species (ROS), and total antioxidant capacity (TAC), representing the sum of enzymatic and nonenzymatic antioxidants, were investigated. Western blotting and reverse transcriptase PCR were used to determine the expression levels of apoptosis-related proteins and genes, including bcl-2, bax, cytochrome c, and capase-3. In the present study, the percentage of apoptotic sperm cells in the exposure group was significantly increased by 91.42% compared with the control group. Moreover, the ROS concentration in exposure group was increased by 46.21%, while the TAC was decreased by 28.01%. Radiation also dramatically decreased the protein and mRNA expression of bcl-2 and increased that of bax, cytochrome c, and capase-3. RF-EMR increases the ROS level and decreases TAC in rat sperm. Excessive oxidative stress alters the expression levels of apoptosis-related genes and triggers sperm apoptosis through bcl-2, bax, cytochrome c and caspase-3 signaling pathways.

Innovative building automation concept for Pumavision Headquarters. Where Pimas are feeling well; Innovatives Gebaeudeautomationskonzept fuer Pumavision Headquarters. Wo Pumas sich wohl fuehlen sollen

Energy Technology Data Exchange (ETDEWEB)

Habermann, Ralf [IPM Gebaeudeleittechnik GmbH, Feucht bei Nuernberg (Germany); Kerz, Thomas [Siemens-Div. Building Technologies Deutschland, Frankfurt am Main (Germany). Business Unit CPS; Vogel, Helmut [Siemens-Div. Building Technologies Deutschland, Muenchen (Germany). Business Unit CPS Region Bayern

2011-03-15

The sport's and lifestyle company PUMA (Herzogenaurach, Federal Republic of Germany) claims the establishment of the first climate neutral corporate headquarter of its industry. Therefore, the electricity for the new 35,000 m{sup 2} large corporate headquarters exclusively results from renewable energy sources. The conversion of this goal is supported by the interdisciplinary building automation system Desigo from Siemens AG (Munich, Federal Republic of Germany). The basic heating and basic cooling of the main building are performed by a concrete core tempering. A part of the heating and cooling is produced by means of two heat pumps.

DHT inhibits the Aβ25-35-induced apoptosis by regulation of seladin-1, survivin, XIAP, bax, and bcl-xl expression through a rapid PI3-K/Akt signaling in C6 glial cell lines.

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Bing, Lelin; Wu, Junfeng; Zhang, Jianfeng; Chen, Yinghui; Hong, Zhen; Zu, Hengbing

2015-01-01

Previous evidences indicate that androgen is neuroprotective in the brain. However, the underling mechanisms remain to be fully elucidated. Moreover, it is controversial whether dihydrotestosterone (DHT) modulates the expression of apoptosis-related effectors, such as survivin, XIAP, bax, and bcl-xl proteins mediated by the PI3-K/Akt pathway, which contributes to androgen neuroprotection. In this study using a C6 glial cell model, apoptotic cells were detected by flow cytometry. Akt, seladin-1, survivin, XIAP, bcl-xl, and bax protein expression is investigated by Western blot. After amyloid β-protein fragment (Aβ25-35) treatment, apoptotic cells at early (annexin V+, PI-) and late (annexin V+, PI+) stages were significantly increased. Apoptosis at early and late was obviously inhibited in the presence of DHT. The effect of DHT was markedly blocked by PI3-K inhibitor LY294002.To elicit the mechanism of DHT protection, the expression of seladin-1, survivin, XIAP, bax, and bcl-xl protein was determined in C6 cells treated with Aβ25-35, DHT, or LY294002. Aβ25-35 significantly downregulated the expression of seladin-1, survivin, XIAP, bcl-xl protein and upregulated the expression of bax protein. DHT significantly inhibited the expression of bax, seladin-1, survivin, XIAP, and bcl-xl protein induced by Aβ25-35. Further, we found the effect of DHT was significantly inhibited by LY294002. Collectively, in a C6 glial cell model, we firstly found that DHT inhibits Aβ25-35-induced apoptosis by a rapid nongenic PI-3K/Akt activation as well as regulation of seladin-1, survivin, XIAP, bcl-xl, and bax proteins.

Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

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Gao, Meili; Li, Yongfei; Ji, Xiaoying; Xue, Xiaochang; Chen, Lan; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Shah, Walayat; Hou, Zhanwu; Kong, Yu

2016-03-01

Epidemiological studies have demonstrated that cigarette smoking is an important cofactor or an independent risk factor for the development of cervical cancer. Benzo(a)pyrene (BaP) is one of the most potent tobacco smoke carcinogens in tobacco smoke. BaP induced DNA damage and over expression in p53 cervical tissue of mice as demonstrated in our previous study. Here we present the findings of exposure to BaP on the expression of Bcl-2, C-myc, Ki-67, Caspase-3 and Bax genes in mouse cervix. Acute intraperitoneal administration of BaP (12.5, 25, 50, 100mg/kg body weight) to ICR female mice induced a significant increase in Bcl-2, C-myc, Ki-67 mRNA and protein level till 72h except in Bcl-2 at 24h with 12.5, 25, 50mg/kg as well as at 48h with 12.5mg/kg body weight post treatment. A significant increase was also seen in Caspase-3 and Bax mRNA and protein level with peak level at 24h and gradual decrease till 72h, however, the expression of caspase-3 increased while that of Bax decreased with increasing dose of Bap after 24h. In sub chronic intraperitoneal and oral gavage administration of BaP (2.5, 5, 10mg/kg body weight), similar significant increase was observed for all the examined genes as compared to the control and vehicle groups, however the expression of Bax decreased in a dose dependent manner. The findings of this study will help in further understanding the molecular mechanism of BaP induced carcinogenesis of cervical cancer. Copyright © 2015 Elsevier GmbH. All rights reserved.

Overexpression of angiopoietin 2 promotes the formation of oral squamous cell carcinoma by increasing epithelial-mesenchymal transition-induced angiogenesis.

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Li, C; Li, Q; Cai, Y; He, Y; Lan, X; Wang, W; Liu, J; Wang, S; Zhu, G; Fan, J; Zhou, Y; Sun, R

2016-09-01

Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck and is associated with a high rate of lymph node metastasis. The initial step in the metastasis and transition of tumors is epithelial-mesenchymal transition (EMT)-induced angiogenesis, which can be mediated by angiopoietin 2 (ANG2), a key regulatory factor in angiogenesis. In the present study, immunohistochemistry and real-time quantitative reverse transcriptase (qRT-PCR) were used to measure the expression of ANG2 in OSCC tissues. Plasmids encoding ANG2 mRNA were used for increased ANG2 expression in the OSCC cell line TCA8113. The short interfering RNA (siRNA)-targeting ANG2 mRNA sequences were used to inhibit ANG2 expression in TCA8113 cells. Subsequently, transwell assays were performed to examine the effects of ANG2 on TCA8113 cell migration and invasion. Furthermore, in vivo assays were performed to assess the effect of ANG2 on tumor growth. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and immunohistochemistry were used to examine cell apoptosis and angiogenesis in tumor tissues, respectively. Finally, western blot analysis was performed to evaluate tumor formation-related proteins in OSCC tissues. We found that protein expression of ANG2 was remarkably upregulated in OSCC tissues. Overexpression of ANG2 increased the migration and invasion of TCA8113 cells by regulating EMT. Further investigations showed that overexpression of ANG2 increased tumor growth in nude mice, and angiogenesis of OSCC tissues increased in the presence of ANG2 overexpression. Overexpression of ANG2 also reduced cell apoptosis in tumor tissue cells. Finally, we found that overexpression of ANG2 resulted in changes in the expression of tumor formation-related proteins including vimentin, E-cadherin, Bim, PUMA, Bcl-2, Bax, Cyclin D1, PCNA and CD31. Our findings show that ANG2 has an important role in the migration and invasion of OSCC. More importantly, further

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

International Nuclear Information System (INIS)

Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

2010-01-01

Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [ 60 Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [ 60 Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [ 60 Co] γ-rays; Group C included cells treated with 8 Gy of [ 60 Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis. Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [ 60 Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with

Characterization of Bc1-2, Bc1-xL, and Bax Pore Formation and Their Role in Apoptosis Regulation

Science.gov (United States)

2002-01-01

Bcl-2, Bcl-xL, and Bax Pore Formation and Their Role in Apoptosis Regulation PRINCIPAL INVESTIGATOR: Frank Stenner -Liewen, Ph.D. Sharon Schendel, Ph.D...AUTHOR(S) Frank Stenner -Liewen, Ph.D. Sharon Schendel, Ph.D. John C. Reed, M.D., Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING

Structural and energetical studies of the adsorption of para and meta-isomers of xylene on pre-hydrated zeolite BaX. Characterization by neutron diffraction and temperature programmed desorption; Etude structurale et energetique de l'adsorption des isomeres para- et meta- du xylene dans la zeolithe BaX prehydratee. Caracterisation par diffraction des neutrons et thermodesorption programmee

Energy Technology Data Exchange (ETDEWEB)

Pichon, Ch.

1999-10-19

The separation of p-xylene from C{sub 8} aromatics is performed industrially by selective adsorption on zeolitic materials. FAU-type zeolites are currently used for this separation and especially the partially hydrated BaX. The aim of this work is to characterize from a structural (by low temperature neutron powder diffraction) and an energetical (by temperature programmed desorption) point of view, the adsorption of para- and meta- isomers of xylene, for different fillings, as pure substances as well as mixtures, on pre-hydrated zeolite BaX. The influence of the water pre-adsorption on xylene adsorption selectivity is carefully discussed. The crystalline structure of the zeolite BaX (framework and compensation of charge cations) and of the adsorbed phase (water, p- and m-xylene molecules) are completely characterized by neutron diffraction. The location and the distribution of water and xylene molecules on their adsorption sites is especially followed as a function of the filling of the zeolite and of the composition of the adsorbed phase. Microscopic measurements were correlated to the energetical analysis (at a macroscopic level) in order to obtain a consistent description of adsorption phenomenon and to propose a possible origin for adsorption selectivity.

Enhanced thermoelectric figure-of-merit in environmentally benign BaxSr2-xTiCoO6 double perovskites

Science.gov (United States)

Saxena, Mandvi; Roy, Pinku; Acharya, Megha; Bose, Imon; Tanwar, Khagesh; Maiti, Tanmoy

2016-12-01

Environmental friendly, non-toxic double perovskite BaxSr2-xTiCoO6 compositions with 0 ≤ x ≤ 0.2 were synthesized using solid-state reaction route for high temperature thermoelectric (TE) applications. XRD and SEM studies confirmed the presence of single-phase solid solution with highly dense microstructure for all the oxide compositions. Temperature dependent electrical conductivity measurement showed semiconductor to metal (M-S) transition in these double perovskites. Incorporation of barium in Sr2TiCoO6 pushed M-S transition to higher temperature making it a potential candidate for high temperature TE applications. Conductivity behaviors of these oxides were explained by small polaron model. Furthermore, these oxides exhibit a glass like behavior resulting in low thermal conductivity. Low temperature dielectric measurement revealed relaxor ferroelectric behavior in these oxides below room temperature. Transition of these relaxors into a glassy state beyond Burns temperature (TD) was found responsible for having low thermal conductivity in these oxides. Maximum dimensionless TE figure-of-merit ZT = 0.29 at 1223 K was achieved for BaxSr2-xTiCoO6 composition with x = 0.2.

RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

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Toshinori Ozaki

2013-01-01

Full Text Available A proper DNA damage response (DDR, which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such as p21WAF1, BAX, and PUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2/Bax expression.

Science.gov (United States)

Liu, Qing-Shan; Deng, Ran; Li, Shuran; Li, Xu; Li, Keqin; Kebaituli, Gulibanumu; Li, Xueli; Liu, Rui

2017-08-01

An oxygen-glucose deprivation and reoxygenation model in primary cultured rat cortical neurons was developed for this study to investigate the effects of ellagic acid (EA), a low-molecular-weight polyphenol, on neuron cells and their function, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent. Administration of EA significantly decreased the volume of cerebrum infarction and the neurological deficit scores of the rats; EA treatment also increased the number of Bcl-2-positive cells and the ratio of Bcl-2-positive to Bax-positive neurons in the semidarkness zone near the brain ischemic focus in the photothrombotic cerebral ischemia model. Treatment of EA resulted in increased neuron viability, cell nuclear integrity, and the ratio of Bcl-2/Bax expression in the primary cultured neuron model; EA treatment also lead to a decrease in the number of apoptotic cells. Our results therefore suggest a specific mechanism for the beneficial effects of EA, providing new insights into how it provides neuroprotection. To the best of our knowledge, these results represent new insights on the mechanisms of the brain cell protective activity of EA. Thus, EA may be used in functional foods or medicines to help treat nerve dysfunction, neurodegenerative disease, and aging.

Eletrocardiografia em onças-pardas (Puma concolor anestesiadas com sevoflurano ou isoflurano

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A.R. Oliveira

Full Text Available RESUMO O objetivo deste trabalho foi descrever os achados eletrocardiográficos de 11 onças- pardas (Puma concolor. Os animais foram sedados com 0,15mg/kg de detomidina associado a 5mg/kg de cetamina e mantidos anestesiados com sevoflurano (GSEVO, n=6 ou isoflurano (GISO, n=5. A frequência cardíaca foi de 95 ± 13bpm. As alterações observadas nos animais no GSEVO foram: atrial standtill com condução ventricular, episódios isolados de contração ventricular prematura, bloqueio atrioventricular de primeiro grau, diminuição da amplitude do complexo QRS, onda S profunda e aumento da amplitude da onda T. No grupo GISO, observou-se bloqueio de ramo direito do feixe de His, bloqueio atrioventricular de primeiro grau e aumento da amplitude da onda T. Arritmias não puderam ser associadas ao uso dos anestésicos inalatórios devido à não sensibilização do miocárdio às catecolaminas. Achados como o BAV de primeiro grau pode ter ocorrido devido ao uso de agonistas α-2 adrenérgicos. Este estudo aumentou o conhecimento sobre as alterações eletrocardiográficas em onças-pardas anestesiadas, entretanto mais estudos são necessários para correlacionar estes achados ao uso de agentes anestésicos.

Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats

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Wendy S. Sprague

2018-04-01

Full Text Available We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV and then infected with pathogenic feline immunodeficiency virus (FIV (co-infection with the host adapted/pathogenic virus had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Science.gov (United States)

He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

2014-05-01

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

[Distribution of Pathogenic Bacteria and Its Influence on Expression of BCL-2 and BAX Protein after HSCT in the Patients with Hematological Malignancies].

Science.gov (United States)

Su, Gui-Ping; Dai, Yan; Huang, Lai-Quan; Jiang, Yi-Zhi; Geng, Liang-Quan; Ding, Kai-Yang; Huang, Dong-Ping

2016-06-01

To investigate the distribution of pathogenic bacteria in the patients with hematologic malignancies received hematopoietic stem cell transplantation (HSCT) and its influence on the expression of BCL-2 and BAX proteins. The clinical data of 64 patients with malignant lymphoma (ML) received auto-HSCT from January 2011 to December 2015 in our hospital were analyzed. On basis of post-treansplant infection, the patients were divided into infection group (36 cases) and non-infection group (28 cases). The distribution of pathogenic bacteria in 2 groups was identified, the T lymphocyte subsets of peripheral blood, expression level of apoptotic proteins and C-reaction protein (CRP) in 2 group were detected. Thirty-six strains of pathogenic bacteria were isolated from 36 case of hematological malignancy after HSCT, including 24 strains of Gram-negative bacteria (66.67%) with predominamce of klebsiella pneumoniae (19.44%). The periperal blood CD4+ (t=2.637, Ppathogenic bacteria infecting ML patients after HSCT were mainly Gram-negative bacteria. The post-transplant infection can promote the expression up-regulation of related inflammatory factors and apoptotic proteins. The pathogens may be involved in cell apoptisis that provides a new strategy to treat the hematologic malignancies.

Pushing the size limit of de novo structure ensemble prediction guided by sparse SDSL-EPR restraints to 200 residues: The monomeric and homodimeric forms of BAX

Science.gov (United States)

Fischer, Axel W.; Bordignon, Enrica; Bleicken, Stephanie; García-Sáez, Ana J.; Jeschke, Gunnar; Meiler, Jens

2016-01-01

Structure determination remains a challenge for many biologically important proteins. In particular, proteins that adopt multiple conformations often evade crystallization in all biologically relevant states. Although computational de novo protein folding approaches often sample biologically relevant conformations, the selection of the most accurate model for different functional states remains a formidable challenge, in particular, for proteins with more than about 150 residues. Electron paramagnetic resonance (EPR) spectroscopy can obtain limited structural information for proteins in well-defined biological states and thereby assist in selecting biologically relevant conformations. The present study demonstrates that de novo folding methods are able to accurately sample the folds of 192-residue long soluble monomeric Bcl-2-associated X protein (BAX). The tertiary structures of the monomeric and homodimeric forms of BAX were predicted using the primary structure as well as 25 and 11 EPR distance restraints, respectively. The predicted models were subsequently compared to respective NMR/X-ray structures of BAX. EPR restraints improve the protein-size normalized root-mean-square-deviation (RMSD100) of the most accurate models with respect to the NMR/crystal structure from 5.9 Å to 3.9 Å and from 5.7 Å to 3.3 Å, respectively. Additionally, the model discrimination is improved, which is demonstrated by an improvement of the enrichment from 5% to 15% and from 13% to 21%, respectively. PMID:27129417

Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

Science.gov (United States)

Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

2015-01-01

Purpose Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Materials and methods Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Results Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. Conclusion These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis

Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus.

Science.gov (United States)

Del Puerto, H L; Martins, A S; Moro, L; Milsted, A; Alves, F; Braz, G F; Vasconcelos, A C

2010-01-26

Canine distemper is an immunosuppressive disease caused by the canine distemper virus (CDV). Pathogenesis mainly involves the central nervous system and immunosuppression. Dogs naturally infected with CDV develop apoptotic cells in lymphoid tissues and the cerebellum, but this apoptotic mechanism is not well characterized. To better understand this process, we evaluated the expression of Bax, Bcl-2, and caspase-3, -8 and -9, by evaluating mRNA levels in the peripheral blood, lymph nodes and cerebellum of CDV-infected (CDV+) and uninfected (CDV-) dogs by real-time polymerase chain reaction (PCR). Blood samples from 12 CDV+ and 8 CDV- dogs, diagnosed by reverse transcription-PCR, were subjected to hematological analysis and apoptotic gene expression was evaluated using real-time-PCR. Tissues from the cerebellum and lymph nodes of four CDV+ and three CDV-dogs were also subjected to real time-PCR. No significant differences were found between CDV+ and CDV- dogs in the hemotological results or in the expression of caspase-3, -8, -9, Bax, and Bcl-2 in the peripheral blood. However, expression of Bax, caspase-3, -8 and -9 was significantly higher in the cerebellum of CDV+ compared to CDV- dogs. Expression of caspase-3 and -8 was significantly higher in the lymph nodes of CDV+ compared to CDV- dogs. We concluded that infection with CDV induces apoptosis in the cerebellum and lymph nodes in different ways. Lymph node apoptosis apparently occurs via caspase-3 activation, through the caspase-8 pathway, and cerebellum apoptosis apparently occurs via caspase-3 activation, through the caspase-8 and mitochondrial pathways.

Lithium chloride attenuates mitomycin C induced necrotic cell death in MDA-MB-231 breast cancer cells via HMGB1 and Bax signaling.

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Razmi, Mahdieh; Rabbani-Chadegani, Azra; Hashemi-Niasari, Fatemeh; Ghadam, Parinaz

2018-07-01

The clinical use of potent anticancer drug mitomycin C (MMC) has limited due to side effects and resistance of cancer cells. The aim of this study was to investigate whether lithium chloride (LiCl), as a mood stabilizer, can affect the sensitivity of MDA-MB-231 breast cancer cells to mitomycin C. The cells were exposed to various concentrations of mitomycin C alone and combined with LiCl and the viability determined by trypan blue and MTT assays. Proteins were analyzed by western blot and mRNA expression of HMGB1 MMP9 and Bcl-2 were analyzed by RT-PCR. Flow cytometry was used to determine the cell cycle arrest and percent of apoptotic and necrotic cells. Concentration of Bax assessed by ELISA. Exposure of the cells to mitomycin C revealed IC 50 value of 20 μM, whereas pretreatment of the cells with LiCl induced synergistic cytotoxicity and IC 50 value declined to 5 μM. LiCl combined with mitomycin C significantly down-regulated HMGB1, MMP9 and Bcl-2 gene expression but significantly increased the level of Bax protein. In addition, the content of HMGB1 in the nuclei decreased and pretreatment with LiCl reduced the content of HMGB1 release induced by MMC. LiCl increased mitomycin C-induced cell shrinkage and PARP fragmentation suggesting induction of apoptosis in these cells. LiCl prevented mitomycin C-induced necrosis and changed the cell death arrest at G2/M-phase. Taking all together, it is suggested that LiCl efficiently enhances mitomycin C-induced apoptosis and HMGB1, Bax and Bcl-2 expression may play a major role in this process, the findings that provide a new therapeutic strategy for LiCl in combination with mitomycin C. Copyright © 2018 Elsevier GmbH. All rights reserved.

Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

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Song, Y; Zhong, M; Cai, F-C

2018-01-01

Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (pOxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas A expressão imuno-histoquímica das proteínas p53, BCL-2, BAX e VEGFR1 em nefroblastomas

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Ana Paula Percicote

2013-02-01

Full Text Available INTRODUCTION: Nephroblastoma or Wilms' tumor is the most frequent renal cancer in children. Although its prognosis is favorable for most patients, it may relapse or have a fatal outcome. The characterization of risk groups by applying immunohistochemical biomarkers aims to adapt the treatment to its corresponding group as well as to reduce relapses and fatal outcome. p53, B-cell lymphoma 2 (BCL-2, BCL-2 associated protein X (BAX and vascular endothelial growth factor receptor 1 (VEGFR1 are among the most widely studied biomarkers, which are related to the apoptotic pathway, DNA repair and neovascularization. OBJECTIVE: The objective of this study is to assess the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 in samples of human nephroblastoma and to correlate them with clinicopathological prognostic factors. MATERIAL AND METHODS: Twenty-nine surgical specimens of nephroblastoma diagnosed from 1994 to 2007 were selected from the Anatomopathological Service of two hospitals in Curitiba. The immunohistochemical analysis of tissue microarrays was performed through immunoperoxidase staining and the yielded results were compared with clinicopathological prognostic factors. RESULTS: The major immunohistochemical expression of VEGFR1 in blastema and epithelium presented positive association with the risk group. Hence this may be related to higher vascular neoplastic invasion apparently caused by the endothelial growth factor, which maximizes the chances of metastasis and ultimately changes tumor staging, risk group and clinical evolution. CONCLUSIONS: The immunohistochemical expression of VEGFR1 substantiated a directly proportional association with the nephroblastoma risk group.INTRODUÇÃO: O nefroblastoma, ou tumor de Wilms, é a neoplasia renal mais frequente na infância. Embora o prognóstico seja favorável para a maioria dos pacientes, muitos evoluem para recidiva ou óbito. A caracterização de grupos de risco por meio de

Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway.

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Deng, Lin; Adachi, Tetsuya; Kitayama, Kikumi; Bungyoku, Yasuaki; Kitazawa, Sohei; Ishido, Satoshi; Shoji, Ikuo; Hotta, Hak

2008-11-01

We previously reported that cells harboring the hepatitis C virus (HCV) RNA replicon as well as those expressing HCV NS3/4A exhibited increased sensitivity to suboptimal doses of apoptotic stimuli to undergo mitochondrion-mediated apoptosis (Y. Nomura-Takigawa, et al., J. Gen. Virol. 87:1935-1945, 2006). Little is known, however, about whether or not HCV infection induces apoptosis of the virus-infected cells. In this study, by using the chimeric J6/JFH1 strain of HCV genotype 2a, we demonstrated that HCV infection induced cell death in Huh7.5 cells. The cell death was associated with activation of caspase 3, nuclear translocation of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. These results suggest that HCV-induced cell death is, in fact, apoptosis. Moreover, HCV infection activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change and its increased accumulation on mitochondrial membranes. Concomitantly, HCV infection induced disruption of mitochondrial transmembrane potential, followed by mitochondrial swelling and release of cytochrome c from mitochondria. HCV infection also caused oxidative stress via increased production of mitochondrial superoxide. On the other hand, HCV infection did not mediate increased expression of glucose-regulated protein 78 (GRP78) or GRP94, which are known as endoplasmic reticulum (ER) stress-induced proteins; this result suggests that ER stress is not primarily involved in HCV-induced apoptosis in our experimental system. Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s).

BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice.

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Cook, Matthew S; Coveney, Douglas; Batchvarov, Iordan; Nadeau, Joseph H; Capel, Blanche

2009-04-15

A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1(Ter/Ter)) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-specific phenotype variation. To determine the mechanism underlying early PGC loss we crossed Dnd1(Ter/Ter) embryos to a Bax-null background and found that germ cells were partially rescued. Surprisingly, on a mixed genetic background, rescued male germ cells also generated fully developed teratomas at a high rate. Double-mutant females on a mixed background did not develop teratomas, but were fertile and produced viable off-spring. However, when Dnd1(Ter/Ter) XX germ cells developed in a testicular environment they gave rise to the same neoplastic clusters as mutant XY germ cells in a testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background.

Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway

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Li, Fengbo [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Graduate School of Tianjin Medical University, No. 22, Qixiangtai Street, Heping District, Tianjin 300070 (China); Sun, Xiaolei; Ma, Jianxiong [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Ma, Xinlong, E-mail: gengxiao502@163.com [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Zhao, Bin; Zhang, Yang; Tian, Peng [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China); Li, Yanjun [Graduate School of Tianjin Medical University, No. 22, Qixiangtai Street, Heping District, Tianjin 300070 (China); Han, Zhe [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin TJ 300050 (China)

2014-09-26

Highlights: • Naringin possesses many pharmacological activities, promotes the proliferation of osteoblast. • Undecalcified histological obtain dynamic parameters of callus formation and remodeling. • Naringin regulate osteoclast apoptosis by mitochondrial pathway. - Abstract: Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.

Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway

International Nuclear Information System (INIS)

Li, Fengbo; Sun, Xiaolei; Ma, Jianxiong; Ma, Xinlong; Zhao, Bin; Zhang, Yang; Tian, Peng; Li, Yanjun; Han, Zhe

2014-01-01

Highlights: • Naringin possesses many pharmacological activities, promotes the proliferation of osteoblast. • Undecalcified histological obtain dynamic parameters of callus formation and remodeling. • Naringin regulate osteoclast apoptosis by mitochondrial pathway. - Abstract: Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

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Mao Xinggang

2010-12-01

Full Text Available Abstract Background Boron neutron capture therapy (BNCT is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU in China. Human glioma cells (the U87, U251, and SHG44 cell lines were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM. The apoptosis rate was detected by flow cytometer (FCM. The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P 60Co] γ-rays (P P Conclusions Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by

Sheeppox virus SPPV14 encodes a Bcl-2-like cell death inhibitor that counters a distinct set of mammalian proapoptotic proteins.

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Okamoto, Toru; Campbell, Stephanie; Mehta, Ninad; Thibault, John; Colman, Peter M; Barry, Michele; Huang, David C S; Kvansakul, Marc

2012-11-01

Many viruses express inhibitors of programmed cell death (apoptosis), thereby countering host defenses that would otherwise rapidly clear infected cells. To counter this, viruses such as adenoviruses and herpesviruses express recognizable homologs of the mammalian prosurvival protein Bcl-2. In contrast, the majority of poxviruses lack viral Bcl-2 (vBcl-2) homologs that are readily identified by sequence similarities. One such virus, myxoma virus, which is the causative agent of myxomatosis, expresses a virulence factor that is a potent inhibitor of apoptosis. In spite of the scant sequence similarity to Bcl-2, myxoma virus M11L adopts an almost identical 3-dimensional fold. We used M11L as bait in a sequence similarity search for other Bcl-2-like proteins and identified six putative vBcl-2 proteins from poxviruses. Some are potent inhibitors of apoptosis, in particular sheeppox virus SPPV14, which inhibited cell death induced by multiple agents. Importantly, SPPV14 compensated for the loss of antiapoptotic F1L in vaccinia virus and acts to directly counter the cell death mediators Bax and Bak. SPPV14 also engages a unique subset of the death-promoting BH3-only ligands, including Bim, Puma, Bmf, and Hrk. This suggests that SPPV14 may have been selected for specific biological roles as a virulence factor for sheeppox virus.

Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

International Nuclear Information System (INIS)

Naumov, Inna; Kazanov, Dina; Lisiansky, Victoria; Starr, Alex; Aroch, Ilan; Shapira, Shiran; Kraus, Sarah; Arber, Nadir

2012-01-01

Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35–40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1 and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our “gene therapy” approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce ∼ 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by ∼ 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.

Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

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Naumov, Inna [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Kazanov, Dina [Integrated Cancer Prevention Center, Tel Aviv (Israel); Lisiansky, Victoria [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Starr, Alex [Lung and Allergy Institute, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aroch, Ilan; Shapira, Shiran; Kraus, Sarah [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Arber, Nadir, E-mail: narber@post.tau.ac.il [Integrated Cancer Prevention Center, Tel Aviv (Israel); Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

2012-01-15

Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35-40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1 and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our 'gene therapy' approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce {approx} 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by {approx} 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.

BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast.

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Juhásová, Barbora; Mentel, Marek; Bhatia-Kiššová, Ingrid; Zeman, Igor; Kolarov, Jordan; Forte, Michael; Polčic, Peter

2011-09-02

Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X(L) are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary

NARCIS (Netherlands)

Slot, K.A.; Voorendt, M.; Boer-Brouwer, de M.; Vugt, van H.H.; Teerds, K.J.

2006-01-01

In the present investigation, the localization of proteins involved in ovarian apoptosis were studied throughout the estrous cycle in the presence of fluctuating hormone levels. Fas, Fas ligand, Bcl-2, Bax and caspase-3 mRNA expression and proteins were detected in all ovarian tissue extracts,

Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.

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Bermudez-Hernandez, Keria; Lu, Yi-Ling; Moretto, Jillian; Jain, Swati; LaFrancois, John J; Duffy, Aine M; Scharfman, Helen E

2017-09-01

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.

Hsp105 family proteins suppress staurosporine-induced apoptosis by inhibiting the translocation of Bax to mitochondria in HeLa cells

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Yamagishi, Nobuyuki; Ishihara, Keiichi; Saito, Youhei; Hatayama, Takumi

2006-01-01

Hsp105 (Hsp105α and Hsp105β), major heat shock proteins in mammalian cells, belong to a subgroup of the HSP70 family, HSP105/110. Previously, we have shown that Hsp105α has completely different effects on stress-induced apoptosis depending on cell type. However, the molecular mechanisms by which Hsp105α regulates stress-induced apoptosis are not fully understood. Here, we established HeLa cells that overexpress either Hsp105α or Hsp105β by removing doxycycline and examined how Hsp105 modifies staurosporine (STS)-induced apoptosis in HeLa cells. Apoptotic features such as the externalization of phosphatidylserine on the plasma membrane and nuclear morphological changes were induced by the treatment with STS, and the STS-induced apoptosis was suppressed by overexpression of Hsp105α or Hsp105β. In addition, we found that overexpression of Hsp105α or Hsp105β suppressed the activation of caspase-3 and caspase-9 by preventing the release of cytochrome c from mitochondria. Furthermore, the translocation of Bax to mitochondria, which results in the release of cytochrome c from the mitochondria, was also suppressed by the overexpression of Hsp105α or Hsp105β. Thus, it is suggested that Hsp105 suppresses the stress-induced apoptosis at its initial step, the translocation of Bax to mitochondria in HeLa cells

Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation.

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Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Eiseman, Julie; Shiva, Sruti S; Rigatti, Lora H; Singh, Shivendra V

2017-02-01

The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self-renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose-dependently inhibited viability of MDA-MB-231 (triple-negative), MCF-7 (estrogen receptor-positive), and SUM159 (triple-negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF-10A) was fully resistant to LLM-mediated cell growth inhibition and apoptosis induction. LLM also inhibited self-renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM-induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase-9 activation, and (c) cytosolic release of cytochrome c. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5 mg/kg; 5 times/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Diet of margay, Leopardus wiedii, and jaguarundi, Puma yagouaroundi, (Carnivora: Felidae in Atlantic Rainforest, Brazil

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Rita de Cassia Bianchi

2011-02-01

Full Text Available This study identifies the food habits of the margay, Leopardus wiedii (Schinz, 1821, and the jaguarundi, Puma yagouaroundi (É. Geoffroy Saint-Hilare, 1803, in the Vale do Rio Doce Natural Reserve and in the Sooretama Biological Reserve, Espírito Santo, Brazil. We determined the diet of both species by the analysis of scats. Fecal samples were collected from April 1995 to September 2000 and identified based on the presence of hairs that were ingested during self-grooming. Scats were oven-dried and washed on a sieve, and the screened material was identified using a reference collection. Of the 59 fecal samples examined, 30 were confirmed to be from the margay and nine of them from the jaguarundi. Mammals were the most consumed items in the diet of the margay, occurring in 77% of the fecal samples, followed by birds (53% and reptiles (20%. Among the mammals consumed, marsupials (Didelphimorphia were the most common item (66%. In the diet of the jaguarundi, birds were the most consumed items and occurred in 55% of the fecal samples; mammals and reptiles occurred in 41% and in 17% of the fecal samples, respectively. From this work we conclude that the margay and jaguarundi fed mainly upon small vertebrates in the Vale do Rio Doce Natural Reserve and in the Sooretama Biological Reserve. Although sample sizes are therefore insufficient for quantitative comparisons, margays prey more frequently upon arboricolous mammals than jaguarundis, which in turn prey more frequently upon birds and reptiles than margays. This seems to reflect a larger pattern throughout their geographic range

Low-frequency Electronic Transport Noise in La2-xBaxCuO4 Nanowires

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Weis, Adam; Xin, Yizhou; van Harlingen, Dale

2013-03-01

In the pseudogap regime, high temperature superconductors often exhibit electronic structure, such as charge stripes. Charge stripes pinned to disorder have been predicted to contribute to low-frequency resistance fluctuations when sample dimensions are comparable to the size of stripe domains (Carlson, 2006). We are extending our previous studies of resistance fluctuations in YBa2Cu3O7-δ (Bonetti, 2004; Caplan, 2010) to thin films of La-based cuprates expected to have a more stable stripe phase, particularly in the regime near 1/8-filling. We present measurements of the low-frequency electronic transport in La2-xBaxCuO4 nanowires fabricated by pulsed laser deposition and lithographic techniques. We discuss temperature dependence of the power spectral density and its relevance to correlated electron phases above Tc. This research was supported by the DOE-DMS under grant DE-FG02-07ER46453, through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign.

Increase in intracellular PGE2 induces apoptosis in Bax-expressing colon cancer cell

International Nuclear Information System (INIS)

Lalier, Lisenn; Pedelaborde, François; Braud, Christophe; Menanteau, Jean; M Vallette, François; Olivier, Christophe

2011-01-01

NSAIDs exhibit protective properties towards some cancers, especially colon cancer. Yet, it is not clear how they play their protective role. PGE 2 is generally shown as the only target of the NSAIDs anticancerous activity. However, PGE 2 known targets become more and more manifold, considering both the molecular pathways involved and the target cells in the tumour. The role of PGE 2 in tumour progression thus appears complex and multipurpose. To gain understanding into the role of PGE 2 in colon cancer, we focused on the activity of PGE 2 in apoptosis in colon cancer cell lines. We observed that an increase in intracellular PGE 2 induced an apoptotic cell death, which was dependent on the expression of the proapoptotic protein Bax. This increase was induced by increasing PGE 2 intracellular concentration, either by PGE 2 microinjection or by the pharmacological inhibition of PGE 2 exportation and enzymatic degradation. We present here a new sight onto PGE 2 in colon cancer cells opening the way to a new prospective therapeutic strategy in cancer, alternative to NSAIDs

Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation

International Nuclear Information System (INIS)

Zhou, Wei-Jie; Wang, Sheng; Hu, Zhuang; Zhou, Zhen-Yu; Song, Cai-Juan

2015-01-01

Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP response element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer. - Highlights: • CREB and Caspase-3 signaling pathways are involved in the ASP induced breast cancer cells apoptosis. • ROCK1/Mlc signaling pathway plays a critical role in this ASP-mediated apoptosis. • Angelica sinensis polysaccharide (ASP) affected the PARP, Bax, Bcl-2, Bcl-xL and Apaf1 protein expression. • The activation of CREB and ROCK1 promotes caspase-3 activation and apoptosis induced

Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation

Energy Technology Data Exchange (ETDEWEB)

Zhou, Wei-Jie; Wang, Sheng [Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, Kaifeng 475000 (China); Hu, Zhuang, E-mail: zhuanghu475000@sina.com [Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, Kaifeng 475000 (China); Zhengzhou Center for Disease Control and Prevention, Zhengzhou 475000 (China); Zhou, Zhen-Yu; Song, Cai-Juan [Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, Kaifeng 475000 (China); Zhengzhou Center for Disease Control and Prevention, Zhengzhou 475000 (China)

2015-11-20

Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP response element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer. - Highlights: • CREB and Caspase-3 signaling pathways are involved in the ASP induced breast cancer cells apoptosis. • ROCK1/Mlc signaling pathway plays a critical role in this ASP-mediated apoptosis. • Angelica sinensis polysaccharide (ASP) affected the PARP, Bax, Bcl-2, Bcl-xL and Apaf1 protein expression. • The activation of CREB and ROCK1 promotes caspase-3 activation and apoptosis induced

Development of a simple screening tool for opportunistic COPD case finding in primary care in Latin America: The PUMA study.

Science.gov (United States)

López Varela, Maria Victorina; Montes de Oca, Maria; Rey, Alejandra; Casas, Alejandro; Stirbulov, Roberto; Di Boscio, Valentina

2016-10-01

Opportunistic chronic obstructive pulmonary disease (COPD) case finding approaches for high-risk individuals with or without symptoms is a feasible option for disease identification. PUMA is an opportunistic case finding study conducted in primary care setting of Argentina, Colombia, Venezuela and Uruguay. The objectives were to measure COPD prevalence in an at-risk population visiting primary care for any reason, to assess the yield of this opportunistic approach and the accuracy of a score developed to detect COPD. Subjects attending routine primary care visits, ≥40 years of age, current or former smokers or exposed to biomass smoke, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) 50 years, heavy smokers (>30 pack-years), with dyspnoea, and having prior spirometry. A simple score and a weighted score constructed using the following predictive factors: gender, age, pack-years smoking, dyspnoea, sputum, cough and spirometry, had a mean accuracy for detecting COPD (post-BD FEV1 /FVC tool to select subjects for spirometry in primary care. © 2016 Asian Pacific Society of Respirology.

Comparison between a finite difference model (PUMA) and a finite element model (DELFIN) for simulation of the reactor of the atomic power plant of Atucha I; Comparacion entre un modelo de diferencias finitas (PUMA) y uno de elementos finitos (DELFIN) para la simulacion del reactor de la CNA-I (central nuclear Atucha-I)

Energy Technology Data Exchange (ETDEWEB)

Grant, C R [Comision Nacional de Energia Atomica, San Martin (Argentina). Unidad de Actividad Reactores y Centrales Nucleares

1997-12-31

The reactor code PUMA, developed in CNEA, simulates nuclear reactors discretizing space in finite difference elements. Core representation is performed by means a cylindrical mesh, but the reactor channels are arranged in an hexagonal lattice. That is why a mapping using volume intersections must be used. This spatial treatment is the reason of an overestimation of the control rod reactivity values, which must be adjusted modifying the incremental cross sections. Also, a not very good treatment of the continuity conditions between core and reflector leads to an overestimation of channel power of the peripherical fuel elements between 5 to 8 per cent. Another code, DELFIN, developed also in CNEA, treats the spatial discretization using heterogeneous finite elements, allowing a correct treatment of the continuity of fluxes and current among elements and a more realistic representation of the hexagonal lattice of the reactor. A comparison between results obtained using both methods in done in this paper. (author). 4 refs., 3 figs.

[Overexpression of N-myc downstream regulated gene 2 (NDRG2) inhibits proliferation, migration and promotes apoptosis in SW480 rectal cancer cells].

Science.gov (United States)

Li, Zhiqiang; Sun, Yang; Wan, Hongxing; Chai, Fang

2017-01-01

Objective To investigate the role of N-myc downstream regulated gene 2 (NDRG2) gene in the proliferation, migration and apoptosis of rectal cancer cells. Methods Human rectal cancer SW480 cells were cultured and transfected with pCDNA3.1-NDRG2 and empty vector (SW480-Ve). SW480 cells were set as a control group. Cell proliferation was detected in SW480 cells, SW480-Ve cells and SW480-NDRG2 cells by MTT assay; cell migration distance in the three groups at 24, 48, 72 hours was tested by wound healing assay; apoptosis rate was determined in the three groups at 48 hours by flow cytometry; the expressions of Bax, caspase-3, Bcl-2 proteins in the three groups were examined by Western blotting. Results After the cells were cultured for 7 days, cell survival rate in SW480-NDRG2 group was significantly lower than that in SW480 cells and SW480-Ve cells; the cell survival rate decreased gradually with the prolongation of the culture time; and it had no significant difference between SW480-Ve group and SW480 group. Cell migration distance in SW480-NDRG2 group was significantly lower than that in SW480-Ve cells and SW480 cells, and it had also no significant difference between SW480-Ve cells and SW480 cells. The apoptosis rate in SW480-NDRG2 group was significantly higher than that in SW480 group and SW480-Ve group, and SW480 cells and SW480-Ve cells had no significant difference in the rate. The expressions of Bax and caspase-3 proteins in SW480-NDRG2 group were significantly higher than those in SW480 cells and SW480-Ve cells; Bcl-2 protein expression was significantly lower in SW480-NDRG2 group than in SW480 cells and SW480-Ve cells; and the expressions of Bax, caspase-3 and Bcl-2 proteins were not significantly different between SW480 cells and SW480-Ve cells. Conclusion Overexpression of NDRG2 can inhibit the proliferation, reduce cell migration, and promote cell apoptosis by regulating the expressions of Bcl-2, Bax and caspase-3 proteins in SW480 cells.

Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats

Science.gov (United States)

Choudhary, Arbind Kumar; Devi, Rathinasamy Sheela

2016-01-01

Abstract Aspartame, a “first generation sweetener”, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes. PMID:27845306

Pride diaries: sex, brain size and sociality in the African lion (Panthera leo) and cougar (Puma concolor).

Science.gov (United States)

Arsznov, Bradley M; Sakai, Sharleen T

2012-01-01

The purpose of this study was to examine if differences in social life histories correspond to intraspecific variation in total or regional brain volumes in the African lion (Panthera leo) and cougar (Puma concolor). African lions live in gregarious prides usually consisting of related adult females, their dependent offspring, and a coalition of immigrant males. Upon reaching maturity, male lions enter a nomadic and often, solitary phase in their lives, whereas females are mainly philopatric and highly social throughout their lives. In contrast, the social life history does not differ between male and female cougars; both are solitary. Three-dimensional virtual endocasts were created using computed tomography from the skulls of 14 adult African lions (8 male, 6 female) and 14 cougars (7 male, 7 female). Endocranial volume and basal skull length were highly correlated in African lions (r = 0.59, p African lions or cougars. However, relative anterior cerebrum volume comprised primarily of frontal cortex and surface area was significantly greater in female African lions than males, while relative posterior cerebrum volume and surface area was greater in males than females. These differences were specific to the neocortex and were not found in the solitary cougar, suggesting that social life history is linked to sex-specific neocortical patterns in these species. We further hypothesize that increased frontal cortical volume in female lions is related to the need for greater inhibitory control in the presence of a dominant male aggressor. Copyright © 2012 S. Karger AG, Basel.

Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation

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Po-Sheng Yang

2015-01-01

Full Text Available Antrodia camphorata (A. camphorata is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO rats. A selective occlusion of the middle cerebral artery (MCA with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone or combined with aspirin (5 mg/kg/day. To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS, haem oxygenase-1 (HO-1, and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P<0.001, iNOS (P<0.001, and Bax (P<0.01 in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day. Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P<0.01. Moreover, treatment of A. camphorata significantly (P<0.05 reduced fenton reaction-induced hydroxyl radical (OH• formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH• signals.

BAX INHIBITOR-1 is required for full susceptibility of barley to powdery mildew.

Science.gov (United States)

Eichmann, Ruth; Bischof, Melanie; Weis, Corina; Shaw, Jane; Lacomme, Christophe; Schweizer, Patrick; Duchkov, Dimitar; Hensel, Götz; Kumlehn, Jochen; Hückelhoven, Ralph

2010-09-01

BAX INHIBITOR-1 (BI-1) is one of the few proteins known to have cross-kingdom conserved functions in negative control of programmed cell death. Additionally, barley BI-1 (HvBI-1) suppresses defense responses and basal resistance to the powdery mildew fungus Blumeria graminis f. sp. hordei and enhances resistance to cell death-provoking fungi when overexpressed in barley. Downregulation of HvBI-1 by transient-induced gene silencing or virus-induced gene silencing limited susceptibility to B. graminis f. sp. hordei, suggesting that HvBI-1 is a susceptibility factor toward powdery mildew. Transient silencing of BI-1 did not limit supersusceptibility induced by overexpression of MLO. Transgenic barley plants harboring an HvBI-1 RNA interference (RNAi) construct displayed lower levels of HvBI-1 transcripts and were less susceptible to powdery mildew than wild-type plants. At the cellular level, HvBI-1 RNAi plants had enhanced resistance to penetration by B. graminis f. sp. hordei. These data support a function of BI-1 in modulating cell-wall-associated defense and in establishing full compatibility of B. graminis f. sp. hordei with barley.

Prognostic value of TP53 transcriptional activity on p21 and bax in patients with esophageal squamous cell carcinomas treated by definitive chemoradiotherapy

International Nuclear Information System (INIS)

Michel, Pierre; Magois, Karine; Robert, Valerie; Chiron, Anne; Lepessot, Florence; Bodenant, Corinne; Roque, Isabelle; Seng, Sok H.; Frebourg, Thierry; Paillot, Bernard

2002-01-01

Purpose: The aim of this study was to evaluate biologic factors on survival and clinical response after definitive concomitant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods and Materials: TP53 protein hyperexpression (immunochemistry [IHC]) and functional assay (FA) of TP53, measuring the ability of TP53 to transactivate p21 and bax reporter systems, were performed in patients with ESCC treated by CRT. The impact of parameters studied on survival and clinical response to CRT was assessed. Results: Thirty-eight patients with ESCC were included. TP53 alterations were detected in 84.2% of cases with FA. All TP53 mutations abolished the transactivation of p21 and bax reporter systems. After CRT, complete response rate was 55.3%. The median survival of the population was 17.5 months. Serum albumin (p=0.002), weight loss <10% (p=0.005), and response to treatment (p<0.001) were significantly linked with survival. TP53 alteration in FA was not significantly predictive of response to CRT (p=0.132) nor survival (p=0.154). Conclusions: Our results suggest that wild-type TP53 in ESCC could be associated with good response to definitive CRT. However, the small rate of ESCC with wild-type TP53 suggests that systematic determination of TP53 status is not appropriate for the management of the ESCC population

Ecologia e conservação da onça parda (Puma concolor Linnaeus, 1771) no Parque Estadual do Rio Doce (PERD) e entorno do Parque Estadual da Serra do Brigadeiro (PESB), Minas Gerais

OpenAIRE

Barros, João Bosco Gonçalves de

2009-01-01

Com a crescente fragmentação da Mata Atlântica, maior bioma brasileiro ameaçado, o entendimento do comportamento de espécies-chave de grande porte como a onça parda (Puma concolor), torna-se importante para elaboração de estratégias de conservação. Neste sentido, os objetivos deste estudo foram avaliar o status de conservação da espécie e de outros felinos de maior porte na região sul do Parque Estadual do Rio Doce (PERD), Marliéria-MG; acompanhamento por técnica de rádio telemetria, de exemp...

Evaluation of cardiopulmonary parameters and recovery from anesthesia in cougars (Puma concolor anesthetized with detomidine/ketamine and isoflurane or sevoflurane

Directory of Open Access Journals (Sweden)

Verônica B. Albuquerque

2016-01-01

Full Text Available Abstract: The aim of this study was to assess the cardiopulmonary effects, the onset time after the administration of a detomidine/ketamine combination, and the recovery from anesthesia of cougars (Puma concolor anesthetized with detomidine/ketamine and isoflurane or sevoflurane for abdominal ultrasound imaging. Fourteen animals were randomly allocated into two experimental groups: GISO (n=7 and GSEVO (n=7. Chemical restraint was performed using 0.15mg/kg detomidine combined with 5mg/kg ketamine intramuscularly; anesthesia induction was achieved using 2mg/kg propofol intravenously and maintenance with isoflurane (GISO or sevoflurane (GSEVO. The following parameters were assessed: heart rate, respiratory rate, systolic and diastolic arterial blood pressure, mean arterial blood pressure, oxyhemoglobin saturation, rectal temperature, central venous pressure, and end-tidal carbon dioxide. The time to sternal recumbency (TSR and time to standing position (TSP were also determined. There was not statistically significant difference for the cardiopulmonary variables or TSP whereas TSR was significantly shorter in GSEVO. The time to onset of anesthesia was 11.1±1.2 minutes and 11.3±1.8 minutes for GISO and GSEVO, respectively. The anesthesia of cougars with detomidine/ketamine and isoflurane or sevoflurane was conducted with safety, cardiopulmonary stability, and increased time to sternal recumbency in the GISO group.

The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized

OpenAIRE

van Delft, Mark F.; Wei, Andrew H.; Mason, Kylie D.; Vandenberg, Cassandra J.; Chen, Lin; Czabotar, Peter E.; Willis, Simon N.; Scott, Clare L.; Day, Catherine L.; Cory, Suzanne; Adams, Jerry M.; Roberts, Andrew W.; Huang, David C.S.

2006-01-01

Since apoptosis is impaired in malignant cells overexpressing pro-survival Bcl-2 proteins, drugs mimicking their natural antagonists, BH3-only proteins, might overcome chemoresistance. Of seven putative BH3 mimetics tested, only ABT-737 triggered Bax/Bak-mediated apoptosis. Despite its high affinity for Bcl-2, Bcl-xL and Bcl-w, many cell types proved refractory to ABT-737. We show that this resistance reflects its inability to target another pro-survival relative, Mcl-1. Down-regulation of Mc...

SURGICAL MANAGEMENT OF APPENDICULAR LONG-BONE FRACTURES IN FREE-RANGING FLORIDA PANTHERS ( PUMA CONCOLOR CORYI): SIX CASES (2000-2014).

Science.gov (United States)

Au Yong, Jo Anne; Lewis, Daniel D; Citino, Scott B; Cunningham, Mark W; Cross, Alan R; Farese, James P; Pablo, Luisito S

2018-03-01

The clinical outcomes of six free-ranging Florida panthers ( Puma concolor coryi) that underwent surgical stabilization of appendicular long-bone fractures (three femoral fractures, one tibial and one tibial and fibular fracture and two radial and ulnar fractures) were evaluated. These panthers presented to the University of Florida from 2000-2014. Estimated age of the panthers ranged from 0.5 to 4.5 yr, and weights ranged from 22 to 65 kg. Causes of injuries were vehicular collision ( n = 4) and capture related ( n = 2). All panthers underwent open reduction and fracture stabilization. Fixation failure necessitated three subsequent surgeries in one panther. Five panthers survived the immediate postoperative period, and all of these panthers' fractures obtained radiographic union (range, 8-36 [mean, 22] wk). The five surviving panthers underwent convalescence for 7-14 mo at White Oak Conservation Center before being released back into the wild; however, one panther was killed when hit by a car 3 days after release. The remaining four panthers were tracked for up to 106 mo in the wild and successfully integrated back into the native population. Surgical stabilization of appendicular long-bone fractures in free-ranging Florida panthers can be successful, but must take into account the stress that a large, undomesticated felid will place on the stabilized limb during convalescence as well as the difficulties involved in rehabilitating a wild panther in captivity.

Hábito alimentar e interferência antrópica na atividade de marcação territorial do Puma concolor e Leopardus pardalis (Carnivora: Felidae e outros carnívoros na Estação Ecológica de Juréia-Itatins, São Paulo, Brasil Food habits and anthropic interference on the territorial marking activity of Puma concolor and Leopardus pardalis (Carnivora: Felidae and other carnivores in the Juréia-Itatins Ecological Station, São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Rogério Martins

2008-09-01

Full Text Available Os hábitos alimentares da onça-parda, jaguatirica e outros carnívoros foram estudados na Juréia (80.000 ha, um dos maiores remanescentes de Mata Atlântica do estado de São Paulo. O estudo foi baseado na análise de fezes encontradas durante um período de amostragem de 15 meses e 415 km percorridos. A diversidade de presas encontradas nas fezes foi alta para ambos os felinos, tendo como presas mais importantes da onça-parda em freqüência de ocorrência e biomassa, o cateto e o tatu-de-rabo-mole, e marsupiais na dieta da jaguatirica. Maior freqüência de fezes de carnívoros foi encontrada distante das casas de moradores tradicionais, sugerindo um comportamento territorial evitando a proximidade da presença humana.Food habits of puma, ocelot and other carnivores were studied in Juréia (80.000 ha, one of the largest remnants of Atlantic forest of the state of São Paulo. The study was based on the analysis of scats found during a sampling period of 15 months and 415 km traversed. The diversity of prey found was high for both felines, with higher frequency and estimated biomass of collared peccary and the greater naked-tailed armadillo in the diet of the puma, and marsupials in the diet of the ocelot. The highest frequency of carnivore scats was found distant from traditional households, suggesting avoidance behavior towards human presence.

Comparison between a finite difference model (PUMA) and a finite element model (DELFIN) for simulation of the reactor of the atomic power plant of Atucha I

International Nuclear Information System (INIS)

Grant, C.R.

1996-01-01

The reactor code PUMA, developed in CNEA, simulates nuclear reactors discretizing space in finite difference elements. Core representation is performed by means a cylindrical mesh, but the reactor channels are arranged in an hexagonal lattice. That is why a mapping using volume intersections must be used. This spatial treatment is the reason of an overestimation of the control rod reactivity values, which must be adjusted modifying the incremental cross sections. Also, a not very good treatment of the continuity conditions between core and reflector leads to an overestimation of channel power of the peripherical fuel elements between 5 to 8 per cent. Another code, DELFIN, developed also in CNEA, treats the spatial discretization using heterogeneous finite elements, allowing a correct treatment of the continuity of fluxes and current among elements and a more realistic representation of the hexagonal lattice of the reactor. A comparison between results obtained using both methods in done in this paper. (author). 4 refs., 3 figs

Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes.

Science.gov (United States)

Calin, G A; Gafà, R; Tibiletti, M G; Herlea, V; Becheanu, G; Cavazzini, L; Barbanti-Brodano, G; Nenci, I; Negrini, M; Lanza, G

2000-05-20

Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGFbetaRII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGFbetaRII and BAX first, followed by frameshifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits. Copyright 2000 Wiley-Liss, Inc.

The effect of the ginger on the apoptosis of hippochampal cells according to the expression of BAX and Cyclin D1 genes and histological characteristics of brain in streptozotocin male diabetic rats.

Science.gov (United States)

Molahosseini, A; Taghavi, M M; Taghipour, Z; Shabanizadeh, A; Fatehi, F; Kazemi Arababadi, M; Eftekhar Vaghefe, S H

2016-10-31

Diabetes is the most common endocrine disorder in humans with multiple complications including nervous system damages. The aim of the present study was to determine the effect of ginger extract on apoptosis of the neurons of hippocampus, via evaluation of BAX and Cyclin D1 and also histological analysis, in male diabetic rats. In this experimental study, 60 Wistar rats (220 ± 30gr) were conducted in 5 groups as follow: diabetic group treated with saline (group 1), normal group treated with saline (group 2), diabetic group treated with ginger (group 3), diabetic group treated with ginger-insulin (group 4), diabetic group treated with insulin (group 5). STZ (60 mg/kg) was intraperitoneally used to induce the diabetes. Expression levels of BAX and Cyclin D1 were examined using Real-Time PCR technique and the normality of neurons was evaluated using H&E staining method. The results showed that blood glucose level significantly decreased in group 4 when compared to group 1. In molecular analysis, there was no significant difference between groups regarding the expression of BAX gens, while, the expression of Cyclin D1 were significantly decreased in group 4 compared with group 1. Histological analysis revealed that pathological symptoms were lower in group 4 than the other diabetic groups. The results of present study showed that the ginger in addition to lowering blood sugar level, changes the expression of Cyclin D1 gene and histological characteristics in a positive manner. This means that the ginger may protects neurons of the hippocampus from apoptosis in diabetic patients.

Down-regulation of Akt by methanol extracts of Impatiens balsamina L. promotes apoptosis in human oral squamous cell carcinoma cell lines.

Science.gov (United States)

Shin, Ji-Ae; Ryu, Mi Heon; Kwon, Ki-Han; Choi, BuYoung; Cho, Sung-Dae

2015-07-01

The apoptotic activity of methanol extracts of Impatiens balsamina L. (MEIB) and related mechanisms in human oral squamous cell carcinoma (OSCC) cells have been systematically investigated. The effects of MEIB on human OSCC cell lines were investigated using trypan blue exclusion assay, MTS assay, Western blot, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead assay, Immunohistochemistry, reverse transcription-polymerase chain reaction, and promoter assay. MEIB decreased cell viability and induced apoptosis in HSC-4 cells. Higher levels of p-Akt expression were observed in OSCC than in normal oral mucosa (NOM), and it correlated with poor survival of the patients. MEIB dephosphorylated p-Akt and decreased Akt expression through proteasome-dependent degradation. LY294002 (PI3K inhibitor) decreased p-Akt and Akt, resulting in enhancing MEIB-induced apoptosis. MEIB down-regulated the expression level of survivin protein at the transcriptional level and YM155 (survivin inhibitor) decreased survivin, which facilitated MEIB-induced apoptosis. MEIB and LY294002 significantly increased Bax, thereby inducing the conformational change, mitochondrial translocation, and oligomerization. In addition, MEIB-induced growth inhibition and apoptosis in OSC-20, another human OSCC cells were mediated by regulating Akt and it downstream targets, survivin and Bax. These results suggest that MEIB may serve as a potential drug candidate for the treatment of human OSCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression

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Guodong Liu

2018-02-01

Full Text Available Background/Aims: Ischemia-reperfusion (I/R injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. Methods: Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control or UW solution containing recombinant human apolipoprotein-J (hr clusterin for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1β, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR, and quantitative RT-PCR assays; IL-1β and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. Results: Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1β, and TNF-α, and

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression.

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Liu, Guodong; Zhang, Hongmei; Hao, Fengyun; Hao, Jing; Pan, Lixiao; Zhao, Qing; Wo, Jinshan

2018-01-01

Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control) or UW solution containing recombinant human apolipoprotein-J (hr clusterin) for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1β, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and quantitative RT-PCR assays; IL-1β and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1β, and TNF-α, and the pro-apoptotic gene Bax, while it enhanced the

Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

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Yousif A. Asiri

2010-01-01

Full Text Available Cyclophosphamide (CP is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control and second (probucol groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day, respectively, for two weeks. Animals in the third (CP and fourth (probucol plus CP groups were injected with the same doses of corn oil and probucol (61 mg/kg/day, respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.. The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB (117%, lactate dehydrogenase (LDH (64%, free (69% and esterified cholesterol (42% and triglyceride (69% compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP (40% and ATP/ADP (44% in cardiac

Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation.

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Lee, Chiang-Wen; Yen, Feng-Lin; Ko, Horng-Huey; Li, Shu-Yu; Chiang, Yao-Chang; Lee, Ming-Hsueh; Tsai, Ming-Horng; Hsu, Lee-Fen

2017-07-13

Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.

Alexela välisomanik plaanib lisaraha kaasamist. Eesti on suure raha jaoks ebahuvitav / Hannes Sarv

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Sarv, Hannes

2011-01-01

Alexela Logisticsi omanikeringi kuuluv Puma Energy plaanib minna börsile. Puma Energy äripartneri Heiti Hääle sõnul Puma oma tegevust Eestis laiendama ei tõtta, sest siin pole kuhugi investeerida. Raivo Vare kommentaare

On the Sr1−xBaxFeO2F Oxyfluoride Perovskites: Structure and Magnetism from Neutron Diffraction and Mössbauer Spectroscopy

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García-Ramos, Crisanto A.; Retuerto, María; Alonso, José Antonio

2016-01-01

Four oxyfluorides of the title series (x = 0.00, 0.25, 0.50, 0.75) have been stabilized by topotactic treatment of perovskite precursors Sr1−xBaxFeO3−δ prepared by soft-chemistry procedures, yielding reactive materials that can easily incorporate a substantial amount of F atoms at moderate temperatures, thus avoiding the stabilization of competitive SrF2 and BaF2 parasitic phases. XRD and Neutron Powder Diffraction (NPD) measurements assess the phase purity and yield distinct features concerning the unit cell parameters’ variation, the Sr and Ba distribution, the stoichiometry of the anionic sublattice and the anisotropic displacement factors for O and F atoms. The four oxyfluorides are confirmed to be cubic in all of the compositional range, the unit cell parameters displaying Vergard’s law. All of the samples are magnetically ordered above room temperature; the magnetic structure is always G-type antiferromagnetic, as shown from NPD data. The ordered magnetic moments are substantially high, around 3.5 μB, even at room temperature (RT). Temperature-dependent Mössbauer data allow identifying Fe3+ in all of the samples, thus confirming the Sr1−xBaxFeO2F stoichiometry. The fit of the magnetic hyperfine field vs. temperature curve yields magnetic ordering TN temperatures between 740 K (x = 0.00) and 683 K (x = 0.75). These temperatures are substantially higher than those reported before for some of the samples, assessing for stronger Fe-Fe superexchange interactions for these specimens prepared by fluorination of citrate precursors in mild conditions. PMID:28774089

TUG1 promotes lens epithelial cell apoptosis by regulating miR-421/caspase-3 axis in age-related cataract.

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Li, Guoxing; Song, Huiyang; Chen, Lei; Yang, Weihua; Nan, Kaihui; Lu, Peirong

2017-07-01

Age-related cataract is among the most common chronic disorders of ageing and the apoptosis of lens epithelial cells contributes to non-congenital cataract development. We amid to explore the role of TUG1 and miR-421 in the age-related cataract. The expression level of TUG1, miR-421 and caspase-3 were detected by RT-qPCR. The apoptotic-related protein, caspase-3, Bax and blc-2 were analyzed by western blot. We performed ultraviolet (UV) irradiation to induce SAR01/04 cell apoptosis which was analyzed by flow cytometry. RIP pull-down and luciferase reporter assay were used to verified the combination and regulating among TUG1, miR-421 and caspase-3. Here, we observed that the expression level of TUG1 and caspase-3 in the anterior lens capsules of age-related cataract were significantly higher and miR-421 was significantly lower than that in the normal anterior lens capsules. The apoptosis-related protein, caspase-3, Bax and blc-2 were abnormal expression in the anterior lens capsules of age-related cataract tissue. Our data showed that the expression level of TUG1 and caspase-3 and cell apoptosis rate in SAR01/04 cells treated with UV irradiation was remarkably higher than that in the control. TUG1 negatively regulated miR-421 expression and promoted UV irradiation-induced SAR01/04 cell apoptosis. However, miR-421 inhibitor and pcDNA-caspase-3 could reverse the action of the SRA01/04 cell apoptosis by si-TUG1, which suggested TUG1 promoted UV irradiation-induced apoptosis through downregulating miR-421 expression. Furthermore, this study confirmed TUG1 could been in combination with miR-421, and TUG1 and caspase-3 were both a directly target of miR-421. TUG1 modulated lens epithelial cell apoptosis through miR-421/caspase-3 axis. These findings will offer a novel insight into the pathogenesis of cataract. Copyright © 2017 Elsevier Inc. All rights reserved.

A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

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Alvankarian, Jafar; Yeop Majlis, Burhanuddin

2012-03-01

Rapid prototyping in the design cycle of new microfluidic devices is very important for shortening time-to-market. Researchers are facing the challenge to explore new and suitable substrates with simple and efficient microfabrication techniques. In this paper, we introduce and characterize a UV-curing elastomeric polyurethane methacrylate (PUMA) for rapid prototyping of microfluidic devices. The swelling and solubility of PUMA in different chemicals is determined. Time-dependent measurements of water contact angle show that the native PUMA is hydrophilic without surface treatment. The current monitoring method is used for measurement of the electroosmotic flow mobility in the microchannels made from PUMA. The optical, physical, thermal and mechanical properties of PUMA are evaluated. The UV-lithography and molding process is used for making micropillars and deep channel microfluidic structures integrated to the supporting base layer. Spin coating is characterized for producing different layer thicknesses of PUMA resin. A device is fabricated and tested for examining the strength of different bonding techniques such as conformal, corona treating and semi-curing of two PUMA layers in microfluidic application and the results show that the bonding strengths are comparable to that of PDMS. We also report fabrication and testing of a three-layer multi inlet/outlet microfluidic device including a very effective fluidic interconnect for application demonstration of PUMA as a promising new substrate. A simple micro-device is developed and employed for observing the pressure deflection of membrane made from PUMA as a very effective elastomeric valve in microfluidic devices.

On the Sr1−xBaxFeO2F Oxyfluoride Perovskites: Structure and Magnetism from Neutron Diffraction and Mössbauer Spectroscopy

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Crisanto A. García-Ramos

2016-11-01

Full Text Available Four oxyfluorides of the title series (x = 0.00, 0.25, 0.50, 0.75 have been stabilized by topotactic treatment of perovskite precursors Sr1−xBaxFeO3−δ prepared by soft-chemistry procedures, yielding reactive materials that can easily incorporate a substantial amount of F atoms at moderate temperatures, thus avoiding the stabilization of competitive SrF2 and BaF2 parasitic phases. XRD and Neutron Powder Diffraction (NPD measurements assess the phase purity and yield distinct features concerning the unit cell parameters’ variation, the Sr and Ba distribution, the stoichiometry of the anionic sublattice and the anisotropic displacement factors for O and F atoms. The four oxyfluorides are confirmed to be cubic in all of the compositional range, the unit cell parameters displaying Vergard’s law. All of the samples are magnetically ordered above room temperature; the magnetic structure is always G-type antiferromagnetic, as shown from NPD data. The ordered magnetic moments are substantially high, around 3.5 μB, even at room temperature (RT. Temperature-dependent Mössbauer data allow identifying Fe3+ in all of the samples, thus confirming the Sr1−xBaxFeO2F stoichiometry. The fit of the magnetic hyperfine field vs. temperature curve yields magnetic ordering TN temperatures between 740 K (x = 0.00 and 683 K (x = 0.75. These temperatures are substantially higher than those reported before for some of the samples, assessing for stronger Fe-Fe superexchange interactions for these specimens prepared by fluorination of citrate precursors in mild conditions.

Piperine attenuates UV-R induced cell damage in human keratinocytes via NF-kB, Bax/Bcl-2 pathway: An application for photoprotection.

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Verma, Ankit; Kushwaha, Hari N; Srivastava, Ajeet K; Srivastava, Saumya; Jamal, Naseem; Srivastava, Kriti; Ray, Ratan Singh

2017-07-01

Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties. The study was planned to photoprotective efficacy of PIP in human keratinocyte (HaCaT) cell line. We have assessed the UV-R induced activation of transcription factor NF-κB in coordination with cell death modulators (Bax/Bcl-2 and p21). The LC-MS/MS analysis revealed that PIP was photostable under UV-A/UV-B exposure. PIP (10μg/ml) attenuates the UV-R (A and B) induced phototoxicity of keratinocyte cell line through the restoration of cell viability, inhibition of ROS, and malondialdehyde generation. Further, PIP inhibited UV-R mediated DNA damage, prevented micronuclei formation, and reduced sub-G1 phase in cell cycle, which supported against photogenotoxicity. This study revealed that PIP pretreatment strongly suppressed UV-R induced photodamages. Molecular docking studies suggest that PIP binds at the active site of NF-κB, and thus, preventing its translocation to nucleus. In addition, transcriptional and translational analysis advocate the increased expression of NF-κB and concomitant decrease in IkB-α expression under UV-R exposed cells, favouring the apoptosis via Bax/Bcl-2 and p21 pathways. However, PIP induced expression of IkB-α suppress the NF-κB activity which resulted in suppression of apoptotic marker genes and proteins that involved in photoprotection. Therefore, we suggest the applicability of photostable PIP as photoprotective agent for human use. Copyright © 2017. Published by Elsevier B.V.

Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

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Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

2010-06-15

CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation. 2010 Elsevier Ltd. All rights reserved.

Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells.

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Morgado-Palacin, Lucia; Llanos, Susana; Serrano, Manuel

2012-02-01

Ribosome biogenesis is the most demanding energetic process in proliferating cells and it is emerging as a critical sensor of cellular homeostasis. Upon disturbance of ribosome biogenesis, specific free ribosomal proteins, most notably L11, bind and inhibit Mdm2, resulting in activation of the tumor suppressor p53. This pathway has been characterized in somatic and cancer cells, but its function in embryonic pluripotent cells has remained unexplored. Here, we show that treatment with low doses of Actinomycin D or depletion of ribosomal protein L37, two well-established inducers of ribosomal stress, activate p53 in an L11-dependent manner in mouse embryonic stem cells (ESCs) and in induced pluripotent stem cells (iPSCs). Activation of p53 results in transcriptional induction of p53 targets, including p21, Mdm2, Pidd, Puma, Noxa and Bax. Finally, ribosomal stress elicits L11- and p53-dependent apoptosis in ESCs/iPSCs. These results extend to pluripotent cells the functionality of the ribosomal stress pathway and we speculate that this could be a relevant cellular checkpoint during early embryogenesis.

AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

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Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Hyung Soon; Kang, Gum-Yong; Bang, Joo Young [Center for Biomedical Mass Spectrometry, Diatech Korea Co., Ltd., Seoul (Korea, Republic of); Cho, Eun-Jung [National Research Laboratory for Chromatin Dynamics, College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Youn, Hong-Duk, E-mail: hdyoun@snu.ac.kr [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence and Technology, Seoul National University, Seoul (Korea, Republic of)

2013-02-01

Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells Following Trichostatin A Treatment.

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Chen, Zongjing; Yang, Yunxiu; Liu, Biao; Wang, Benquan; Sun, Meng; Zhang, Ling; Chen, Bicheng; You, Heyi; Zhou, Mengtao

2015-01-01

Histone deacetylase inhibitors represent a promising class of potential anticancer agents for the treatment of human malignancies. In this study, the effects of trichostatin A (TSA) on apoptosis, metastasis-associated gene expression, and activation of the Notch pathway in human pancreatic cancer cell lines were investigated. After treatment with TSA, cell viability and apoptosis were evaluated using the MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, and flow cytometry. Moreover, RT-PCR and western blot analyses were performed to measure the expression levels of apoptosis-associated genes (Bcl-2, Bax, and caspase-3), metastasis-associated genes (E-cadherin, vimentin, and matrix metalloproteinases), and Notch pathway activation (Notch intracellular domain, NICD). The levels of matrix metalloproteinase 2 and NICD were also semi-quantified by immunoassay. Following treatment with TSA for 24 h, PANC-1, SW1990, and MIATACA-2 cells exhibited cell death. The MTT assay revealed that TSA significantly decreased cell viability in a dose-dependent manner in PANC-1 cells. The Hoechst 33258 staining and flow cytometry results evidenced a significant increase in PANC-1 cell apoptosis following TSA treatment. The expression levels of Bax and caspase-3 were increased significantly, whereas Bcl-2 was down-regulated after TSA treatment. In the PANC-1 cells that survived after TSA treatment, the expression levels of vimentin, E-cadherin, and MMP genes were altered by the promotion of potential metastasis and increased expression of NICD. TSA can induce apoptosis of pancreatic cancer cells. In addition, the up-regulation of metastasis-related genes and the activation of the Notch pathway in the survived PANC-1 cells may be associated with a too-low level of TSA or resistance to TSA.

Effect of JTV1 gene on the proliferation and apoptosis of K562 cells and its mechanism

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Yan WU

2011-05-01

Full Text Available Objective To investigate the effect of tumor-suppressing gene JTV1 on proliferation and apoptosis of leukemic K562 cells,and the changes in apoptosis factors Bcl-2,C-myc and Bax genes.Methods The recombinate vector pcDNA3.1-JTV1,and the empty vector pcDNA3.1 were transfected into K562 cells as control.The cell proliferation of K562 cells was evaluated by colony formation assay;the cell cycle and apoptosis rate were assessed by flow cytometry(FCM;the mRNA levels of apoptosis related genes Bax,Bcl-2 and C-myc were determined by RT-PCR;the protein levels of Bax,Bcl-2 and C-myc were assayed by Western Blotting.Results The colony formation assay showed that the proliferation of K562 cells decreased when the expression of JTV1 gene was up-regulated.FCM assay showed that the G phase cells in pcDNA3.1-JTV1 positive transfection group increased compared with that of the control group and the pcDNA3.1 empty vector transfected group,and the differences were statistically significant(P < 0.05.Compared with the control group and the empty vector group,the mRNA transcription level and the protein translation level of Bax gene increased significantly,and the mRNA transcription level and the protein translation level of Bcl-2 and C-myc gene were reduced significantly(P < 0.05.Conclusions The expressions of Bcl-2 and C-myc gene are inhibited when the gene JTV1 is up-regulated,leading to an increase in Bax gene expression,inhibition of K562 cell proliferation,and promotion of tumor cells apoptosis.Over expression of JTV1 gene can inhibit the proliferation of K562 cells and promote cell apoptosis by inhibiting Bcl-2 and C-myc expression and up-regulating that of Bax.

Role of the lattice dynamics in La2-xBaxCuO4 superconductor based on DFT method

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A Tavana

2010-09-01

Full Text Available Electron-phonon coupling parameters are calculated for La2-x BaxCuO4 cuprate superconductor in a wide range of dopings, from undoped to overdoped compounds. In this study we aim to study the quality of such calculations based on DFT method so, the results of σ GGA+U electronic structure calculations are also investigated. The obtained value for electron-phonon coupling is in the same order of previous calculations but, the value obtained for the Hubbard U parameter shows that, such methods are poor in the estimation of electronic correlations to decide about the role of phonons in these compounds based on their results. Moreover, existence of several structural phase transitions with temperature and doping, lead to larger error in these calculations. Based on the calculated phonon dispersions, structural phase transitions can be resulted which shows the ability of DFT in the study of structural properties and the weakness of the strongly correlations in this properties.

Displacement-type ferroelectric transition with magnetic Mn ions in perovskite Sr1-xBaxMnO3

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Sakai, Hideaki; Fujioka, Jun; Fukuda, Tatsuo; Okuyama, Daisuke; Hashizume, Daisuke; Kagawa, Fumitaka; Nakao, Hironori; Murakami, Youich; Arima, Takahisa; Baron, Alfred Q. R.; Taguchi, Yasujiro; Tokura, Yoshinori

2012-02-01

Almost all the proper ferroelectrics with a perovskite structure discovered so far have no d-electrons in the off-center transition metal site, as exemplified by BaTiO3 and Pb(Zr,Ti)O3. This empirical d^0 rule is incompatible with the emergence of magnetism and has significantly restricted the variety of multiferroic materials. In this work, we have discovered a displacement-type ferroelectric transition originating from off-center Mn^4+ ions in antiferromagnetic Mott insulators Sr1-xBaxMnO3. As Ba concentration increases, the perovskite lattice shows the typical soft mode dynamics, and the ferroelectricity shows up for x .45. In addition to the large polarization and high transition temperature comparable to BaTiO3, we demonstrate that the magnetic order suppresses the ferroelectric lattice dilation by ˜70% and increases the soft-phonon energy by ˜50%, indicating gigantic magnetoelectric effects [1]. This work was supported by the FIRST program on ``Quantum Science on Strong Correlation''. [4pt] [1] H. Sakai et al., Phys. Rev. Lett. 107, 137601 (2011).

Overexpression of BAX INHIBITOR-1 Links Plasma Membrane Microdomain Proteins to Stress.

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Ishikawa, Toshiki; Aki, Toshihiko; Yanagisawa, Shuichi; Uchimiya, Hirofumi; Kawai-Yamada, Maki

2015-10-01

BAX INHIBITOR-1 (BI-1) is a cell death suppressor widely conserved in plants and animals. Overexpression of BI-1 enhances tolerance to stress-induced cell death in plant cells, although the molecular mechanism behind this enhancement is unclear. We recently found that Arabidopsis (Arabidopsis thaliana) BI-1 is involved in the metabolism of sphingolipids, such as the synthesis of 2-hydroxy fatty acids, suggesting the involvement of sphingolipids in the cell death regulatory mechanism downstream of BI-1. Here, we show that BI-1 affects cell death-associated components localized in sphingolipid-enriched microdomains of the plasma membrane in rice (Oryza sativa) cells. The amount of 2-hydroxy fatty acid-containing glucosylceramide increased in the detergent-resistant membrane (DRM; a biochemical counterpart of plasma membrane microdomains) fraction obtained from BI-1-overexpressing rice cells. Comparative proteomics analysis showed quantitative changes of DRM proteins in BI-1-overexpressing cells. In particular, the protein abundance of FLOTILLIN HOMOLOG (FLOT) and HYPERSENSITIVE-INDUCED REACTION PROTEIN3 (HIR3) markedly decreased in DRM of BI-1-overexpressing cells. Loss-of-function analysis demonstrated that FLOT and HIR3 are required for cell death by oxidative stress and salicylic acid, suggesting that the decreased levels of these proteins directly contribute to the stress-tolerant phenotypes in BI-1-overexpressing rice cells. These findings provide a novel biological implication of plant membrane microdomains in stress-induced cell death, which is negatively modulated by BI-1 overexpression via decreasing the abundance of a set of key proteins involved in cell death. © 2015 American Society of Plant Biologists. All Rights Reserved.

Molecular detection of viral agents in free-ranging and captive neotropical felids in Brazil.

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Furtado, Mariana M; Taniwaki, Sueli A; de Barros, Iracema N; Brandão, Paulo E; Catão-Dias, José L; Cavalcanti, Sandra; Cullen, Laury; Filoni, Claudia; Jácomo, Anah T de Almeida; Jorge, Rodrigo S P; Silva, Nairléia Dos Santos; Silveira, Leandro; Ferreira Neto, José S

2017-09-01

We describe molecular testing for felid alphaherpesvirus 1 (FHV-1), carnivore protoparvovirus 1 (CPPV-1), feline calicivirus (FCV), alphacoronavirus 1 (feline coronavirus [FCoV]), feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and canine distemper virus (CDV) in whole blood samples of 109 free-ranging and 68 captive neotropical felids from Brazil. Samples from 2 jaguars ( Panthera onca) and 1 oncilla ( Leopardus tigrinus) were positive for FHV-1; 2 jaguars, 1 puma ( Puma concolor), and 1 jaguarundi ( Herpairulus yagouaroundi) tested positive for CPPV-1; and 1 puma was positive for FIV. Based on comparison of 103 nucleotides of the UL24-UL25 gene, the FHV-1 sequences were 99-100% similar to the FHV-1 strain of domestic cats. Nucleotide sequences of CPPV-1 were closely related to sequences detected in other wild carnivores, comparing 294 nucleotides of the VP1 gene. The FIV nucleotide sequence detected in the free-ranging puma, based on comparison of 444 nucleotides of the pol gene, grouped with other lentiviruses described in pumas, and had 82.4% identity with a free-ranging puma from Yellowstone Park and 79.5% with a captive puma from Brazil. Our data document the circulation of FHV-1, CPPV-1, and FIV in neotropical felids in Brazil.

Resource selection and its implications for wide-ranging mammals of the brazilian cerrado.

Science.gov (United States)

Vynne, Carly; Keim, Jonah L; Machado, Ricardo B; Marinho-Filho, Jader; Silveira, Leandro; Groom, Martha J; Wasser, Samuel K

2011-01-01

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing

Resource selection and its implications for wide-ranging mammals of the brazilian cerrado.

Directory of Open Access Journals (Sweden)

Carly Vynne

Full Text Available Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus, giant anteater (Myrmecophaga tridactyla, maned wolf (Chrysocyon brachyurus, jaguar (Panthera onca, and puma (Puma concolor. We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for

Downregulation of the proapoptotic protein MOAP-1 by the UBR5 ubiquitin ligase and its role in ovarian cancer resistance to cisplatin

OpenAIRE

Matsuura, K; Huang, N-J; Cocce, K; Zhang, L; Kornbluth, S

2016-01-01

Evasion of apoptosis allows many cancers to resist chemotherapy. Apoptosis is mediated by the serial activation of caspase family proteins. These proteases are often activated upon the release of cytochrome c from the mitochondria, which is promoted by the proapoptotic Bcl-2 family protein, Bax. This function of Bax is enhanced by the MOAP-1 (modulator of apoptosis protein 1) protein in response to DNA damage. Previously, we reported that MOAP-1 is targeted for ubiquitylation and degradation ...

IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway.

Science.gov (United States)

Chen, Hongbin; Lin, Wei; Zhang, Yixian; Lin, Longzai; Chen, Jianhao; Zeng, Yongping; Zheng, Mouwei; Zhuang, Zezhong; Du, Houwei; Chen, Ronghua; Liu, Nan

2016-07-26

As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1, and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.

Calreticulin is a fine tuning molecule in epibrassinolide-induced apoptosis through activating endoplasmic reticulum stress in colon cancer cells.

Science.gov (United States)

Obakan-Yerlikaya, Pinar; Arisan, Elif Damla; Coker-Gurkan, Ajda; Adacan, Kaan; Ozbey, Utku; Somuncu, Berna; Baran, Didem; Palavan-Unsal, Narcin

2017-06-01

Epibrassinolide (EBR), a member of brassinostreoids plant hormones with cell proliferation promoting role in plants, is a natural polyhydroxysteroid with structural similarity to steroid hormones of vertebrates. EBR has antiproliferative and apoptosis-inducing effect in various cancer cells. Although EBR has been shown to affect survival and mitochondria-mediated apoptosis pathways in a p53-independent manner, the exact molecular targets of EBR are still under investigation. Our recent SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) data showed that the most significantly altered protein after EBR treatment was calreticulin (CALR). CALR, a chaperone localized in endoplasmic reticulum (ER) lumen, plays role in protein folding and buffering Ca 2+ ions. The alteration of CALR may cause ER stress and unfolded protein response correspondingly the induction of apoptosis. Unfolded proteins are conducted to 26S proteasomal degradation following ubiquitination. Our study revealed that EBR treatment caused ER stress and UPR by altering CALR expression causing caspase-dependent apoptosis in HCT 116, HT29, DLD-1, and SW480 colon cancer cells. Furthermore, 48 h EBR treatment did not caused UPR in Fetal Human Colon cells (FHC) and Mouse Embryonic Fibroblast cells (MEF). In addition our findings showed that HCT 116 colon cancer cells lacking Bax and Puma expression still undergo UPR and related apoptosis. CALR silencing and rapamycin co-treatment prevented EBR-induced UPR and apoptosis, whereas 26S proteasome inhibition further increased the effect of EBR in colon cancer cells. All these findings showed that EBR is an ER stress and apoptotic inducer in colon cancer cells without affecting non-malignant cells. © 2017 Wiley Periodicals, Inc.

Apoptosis Induction by Targeting Interferon Gamma Receptor 2 (IFNgammaR2) in Prostate Cancer: Ligand (IFNgamma) Independent Novel Function of IFNgammaR2 as a Bax Inhibitor

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2016-10-01

Cisplatin (2uM, 30 hrs) PN (5uM, 55hrs) + Cisplatin (2uM, 30 hrs) •  Thorough studies are needed to examine the unknown mechanism of IFNgR2 and Bax as well as...mouse xenograft model. Task3: To determine the mechanism of increased IFNγR2 expression in PCa. We found that NFkB inhibitor suppressed IFNγR2 expression...suggesting that hyper-activation of NFkB may be one of the mechanisms of IFNγR2 overexpression in PCa. These results support our hypothesis that

The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

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Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael

2014-12-04

Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P escitalopram + DI/R group was significantly decreased (P escitalopram + DI/R groups (P escitalopram + DI/R group were significantly decreased (P escitalopram + DI/R group (P escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

Ginsenoside Rh2 Induces Human Hepatoma Cell Apoptosisvia Bax/Bak Triggered Cytochrome C Release and Caspase-9/Caspase-8 Activation

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Xiao-Xi Guo

2012-11-01

Full Text Available Ginsenoside Rh2 (G-Rh2 has been shown to induce apoptotic cell death in a variety of cancer cells. However, the details of the signal transduction cascade involved in G-Rh2-induced cell death is unclear. In this manuscript we elucidate the molecular mechanism of G-Rh2-induced apoptosis in human hepatoma SK-HEP-1 cells by demonstrating that G-Rh2 causes rapid and dramatic translocation of both Bak and Bax, which subsequently triggers mitochondrial cytochrome c release and consequent caspase activation. Interestingly, siRNA-based gene inactivation of caspase-8 effectively delays caspase-9 activation and apoptosis induced by G-Rh2, indicating that caspase-8 also plays an important role in the G-Rh2-induced apoptosis program. Taken together, our results indicate that G-Rh2 employs a multi pro-apoptotic pathway to execute cancer cell death, suggesting a potential role for G-Rh2 as a powerful chemotherapeutic agent.

Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-β and mitochondrial signaling pathway.

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Zhu, H-L; Gao, Y-H; Yang, J-Q; Li, J-B; Gao, J

2018-06-01

Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor β2 (TGF-β2) were examined using Western blot assay. LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-β2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-β signaling and mitochondrial signaling pathway.

New World feline APOBEC3 potently controls inter-genus lentiviral transmission.

Science.gov (United States)

Konno, Yoriyuki; Nagaoka, Shumpei; Kimura, Izumi; Yamamoto, Keisuke; Kagawa, Yumiko; Kumata, Ryuichi; Aso, Hirofumi; Ueda, Mahoko Takahashi; Nakagawa, So; Kobayashi, Tomoko; Koyanagi, Yoshio; Sato, Kei

2018-04-10

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals. Here we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved. To the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.

Scaling for integral simulation of thermal-hydraulic phenomena in SBWR during LOCA

Energy Technology Data Exchange (ETDEWEB)

Ishii, M.; Revankar, S.T.; Dowlati, R [Purdue Univ., West Layfayette, IN (United States)] [and others

1995-09-01

A scaling study has been conducted for simulation of thermal-hydraulic phenomena in the Simplified Boiling Water Reactor (SBWR) during a loss of coolant accident. The scaling method consists of a three-level scaling approach. The integral system scaling (global scaling or top down approach) consists of two levels, the integral response function scaling which forms the first level, and the control volume and boundary flow scaling which forms the second level. The bottom up approach is carried out by local phenomena scaling which forms the third level scaling. Based on this scaling study the design of the model facility called Purdue University Multi-Dimensional Integral Test Assembly (PUMA) has been carried out. The PUMA facility has 1/4 height and 1/100 area ratio scaling, corresponding to the volume scaling of 1/400. The PUMA power scaling based on the integral scaling is 1/200. The present scaling method predicts that PUMA time scale will be one-half that of the SBWR. The system pressure for PUMA is full scale, therefore, a prototypic pressure is maintained. PUMA is designed to operate at and below 1.03 MPa (150 psi), which allows it to simulate the prototypic SBWR accident conditions below 1.03 MPa (150 psi). The facility includes models for all components of importance.

Evaluation of bax, bcl-2, p21 and p53 genes expression variations on cerebellum of BALB/c mice before and after birth under mobile phone radiation exposure.

Science.gov (United States)

Ghatei, Najmeh; Nabavi, Ariane Sadr; Toosi, Mohammad Hossein Bahreyni; Azimian, Hosein; Homayoun, Mansour; Targhi, Reza Ghasemnezhad; Haghir, Hossein

2017-09-01

The increasing rate of over using cell phones has been considerable in youths and pregnant women. We examined the effect of mobile phones radiation on genes expression variation on cerebellum of BALB/c mice before and after of the birth. In this study, a mobile phone jammer, which is an instrument to prevent receiving signals between cellular phones and base transceiver stations (two frequencies 900 and 1800 MHz) for exposure was used and twelve pregnant mice (BALB/c) divided into two groups (n=6), first group irradiated in pregnancy period (19th day), the second group did not irradiate in pregnancy period. After childbirth, offspring were classified into four groups (n=4): Group1: control, Group 2: B1 (Irradiated after birth), Group 3: B2 (Irradiated in pregnancy period and after birth), Group 4: B3 (Irradiated in pregnancy period). When maturity was completed (8-10 weeks old), mice were dissected and cerebellum was isolated. The expression level of bax , bcl-2, p21 and p53 genes examined by real-time reverse transcription polymerase chain reaction (Real-Time RT- PCR). The data showed that mobile phone radio waves were ineffective on the expression level of bcl-2 and p53 genes) P >0.05(. Also gene expression level of bax decreased and gene expression level of p21 increased comparing to the control group ( P mobile phone radiations did not induce apoptosis in cells of the cerebellum and the injured cells can be repaired by cell cycle arrest.

Investigating The Kinematics of Canids and Felids

Science.gov (United States)

Sur, D.

2016-12-01

For all organisms, metabolic energy is critical for survival. While moving efficiently is a necessity for large carnivores, the influence of kinematics on energy demand remains poorly understood. We measured the kinematics of dogs, wolves, and pumas to detect any differences in their respective energy expenditures. Using 22 kinematic parameters measured on 78 videos, we used one-way ANOVAs and paired T-tests to compare 5 experimental treatments among gaits in dogs (n=11 in 3 breed groups), wolves (n=2), and pumas (n=2). Across the measured parameters, we found greater kinematic similarity than expected among dog breeds and no trend in any of the 22 parameters regarding the effect of steepness on locomotion mechanics. Similarly, treadmill kinematics were nearly identical to those measured during outdoor movement. However, in 3 inches of snow, we observed significant differences (pwolf. When comparing canids (wolves and dogs) to a felid (pumas), we found that pumas and dogs are the most kinematically distinct (differing in 13 of 22 parameters, compared with 5 of 22 for wolves and pumas). Lastly, compared with wolves, walking pumas had larger head angles (p=0.0025), forelimb excursion angles (p=0.0045), and hindlimb excursion angles (p=0.0327). After comparing the energetics of pumas and dogs with their respective kinematics, we noted that less dynamic kinematics result in energy savings. Through tracking the locations and gait behavior of large carnivores, novel sensor technology can reveal how indoor kinematics applies to wild animals and improve the conservation of these species.

Lithium-Induced Neuroprotection is Associated with Epigenetic Modification of Specific BDNF Gene Promoter and Altered Expression of Apoptotic-Regulatory Proteins

Directory of Open Access Journals (Sweden)

Tushar eDwivedi

2015-01-01

Full Text Available Bipolar disorder (BD, one of the most debilitating mental disorders, is associated with increased morbidity and mortality. Lithium is the first line of treatment option for BD and is often used for maintenance therapy. Recently, the neuroprotective action of lithium has gained tremendous attention, given that BD is associated with structural and functional abnormalities of the brain. However, the precise molecular mechanism by which lithium exerts its neuroprotective action is not clearly understood. In hippocampal neurons, the effects of lithium on neuronal viability against glutamate-induced cytotoxicity, dendritic length and number, and expression and methylation of BDNF promoter exons and expression of apoptotic regulatory genes were studied. In rat hippocampal neurons, lithium not only increased dendritic length and number, but also neuronal viability against glutamate-induced cytotoxicity. While lithium increased the expression of BDNF as well as genes associated with neuroprotection such as Bcl2 and Bcl-XL, it decreased the expression of pro-apoptotic genes Bax, Bad, and caspases 3. Interestingly, lithium activated transcription of specific exon IV to induce BDNF gene expression. This was accompanied by hypomethylation of BDNF exon IV promoter. This study delineates mechanisms by which lithium mediates its effects in protecting neurons.

The MDM2-inhibitor Nutlin-3 synergizes with cisplatin to induce p53 dependent tumor cell apoptosis in non-small cell lung cancer

Science.gov (United States)

Deben, Christophe; Wouters, An; de Beeck, Ken Op; van Den Bossche, Jolien; Jacobs, Julie; Zwaenepoel, Karen; Peeters, Marc; Van Meerbeeck, Jan; Lardon, Filip; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

2015-01-01

The p53/MDM2 interaction has been a well-studied target for new drug design leading to the development of the small molecule inhibitor Nutlin-3. Our objectives were to combine Nutlin-3 with cisplatin (CDDP), a well-known activator of the p53 pathway, in a series of non-small cell lung cancer cell lines in order to increase the cytotoxic response to CDDP. We report that sequential treatment (CDDP followed by Nutlin-3), but not simultaneous treatment, resulted in strong synergism. Combination treatment induced p53's transcriptional activity, resulting in increased mRNA and protein levels of MDM2, p21, PUMA and BAX. In addition we report the induction of a strong p53 dependent apoptotic response and induction of G2/M cell cycle arrest. The strongest synergistic effect was observed at low doses of both CDDP and Nutlin-3, which could result in fewer (off-target) side effects while maintaining a strong cytotoxic effect. Our results indicate a promising preclinical potential, emphasizing the importance of the applied treatment scheme and the presence of wild type p53 for the combination of CDDP and Nutlin-3. PMID:26125230

Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation.

Science.gov (United States)

Zhao, Carolyn Ying; Szekely, Laszlo; Bao, Wenjie; Selivanova, Galina

2010-04-15

Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6-dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6-mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6-mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. (c)2010 AACR.

Relationship between bcl-2, bax, beclin-1, and cathepsin-D proteins during postovulatory follicular regression in fish ovary.

Science.gov (United States)

Morais, Roberto D V S; Thomé, Ralph G; Santos, Hélio B; Bazzoli, Nilo; Rizzo, Elizete

2016-04-01

In fish ovaries, postovulatory follicles (POFs) are key biomarkers of breeding and provide an interesting model for studying the relationship between autophagy and apoptosis. In this study, we investigated the immunohistochemical expression of autophagic and apoptotic proteins to improve the knowledge on the mechanisms regulating ovarian remodeling after spawning. Females from three neotropical fish species kept in captivity were submitted to hormonal induction. After ova stripping, ovarian sections were sampled daily until 5 days postspawning (dps). Similar events of POF regression were detected by histology, terminal transferase-mediated dUTP nick-end labeling (TUNEL), and electron microscopy in the three species: follicular cells hypertrophy, progressive disintegration of the basement membrane, gradual closing of the follicular lumen, theca thickening, and formation of large autophagic vacuoles preceding apoptosis of the follicular cells. Autophagic and apoptotic proteins were assessed by immunohistochemistry. Morphometric analysis of the immunolabeling revealed a more intense reaction for bcl-2 and beclin-1 (BECN1) in POFs at 0 to 1 dps and for bax at 2 to 3 dps (P family, BECN1, and cathepsin-D can be involved in the regulation of ovarian remodeling in teleost fish. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of the effects of tributyltin chloride and triphenyltin chloride on cell proliferation, proapoptotic p53, Bax, and antiapoptotic Bcl-2 protein levels in human breast cancer MCF-7 cell line.

Science.gov (United States)

Fickova, Maria; Macho, Ladislav; Brtko, Julius

2015-06-01

In recent years it was disclosed, that numerous organotin(IV) derivatives have remarkable cytotoxicity against several types of cancer cells. The property to inhibit cell growth makes these compounds promising for antitumor therapy, as the clinical effectiveness of cisplatin is limited by drug resistance and significant side effects. Tributyltin and triphenyltin are known as endocrine disruptors. Moreover, the compounds exert their toxicity in mammals predominantly through nuclear receptor signaling. Here we present the effects of tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) on cell proliferation, expression of proapoptotic p53, Bax, and antiapoptotic Bcl-2 proteins in human breast cancer MCF-7 cell line. Dose and time dependent (24, 48 and 72 h) cell expositions have demonstrated TBT-Cl as more effective in inhibiting MCF-7 cell proliferation than TPT-Cl. Short time treatment with TBT-Cl displayed marked stimulation of p53 protein expression when compared to TPT-Cl. Both organotin compounds displayed similar mild enhancement of Bax protein expression. The 24h exposition of TPT-Cl induced substantial diminution of Bcl-2 protein expression in comparison with both, untreated cells and TBT-Cl treated cells. Our observations indicate that TBT-Cl and TPT-Cl have different antiproliferative potency and distinct impact on expression of apoptosis marker proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Values, animal symbolism, and human-animal relationships associated to two threatened felids in Mapuche and Chilean local narratives.

Science.gov (United States)

Herrmann, Thora M; Schüttler, Elke; Benavides, Pelayo; Gálvez, Nicolas; Söhn, Lisa; Palomo, Nadja

2013-06-13

The Chilean temperate rainforest has been subjected to dramatic fragmentation for agriculture and forestry exploitation. Carnivore species are particularly affected by fragmentation and the resulting resource use conflicts with humans. This study aimed at understanding values and human-animal relationships with negatively perceived threatened carnivores through the disclosure of local stories and Mapuche traditional folktales. Our mixed approach comprised the qualitative analysis of 112 stories on the kodkod cat (Leopardus guigna) and the puma (Puma concolor) collected by students (9-14 years) from 28 schools in the Araucania region within their family contexts, 10 qualitative in-depth interviews with indigenous Mapuche people, 35 traditional Mapuche legends, and the significance of naming found in ethnographic collections. We revealed a quasi-extinction of traditional tales in the current knowledge pool about pumas and kodkods, local anecdotes, however, were present in significant numbers. Values associated to both felids were manifold, ranging from negativistic to positive values. While pumas played an important role in people's spirituality, negative mythological connotations persisted in kodkod stories. Four prominent relationships were derived: (1) Both felids represent threats to livestock, pumas even to life, (2) both felids are symbols for upcoming negative events, (3) pumas are spiritual creatures, and (4) kodkods are threatened by humans. Recommendations are provided for stimulating new ways of perceiving unpopular and threatened carnivores among those who live in vicinity to them.

Caractérisation structurale de l'adsorption des isomères para- et meta- du xylène dans la zéolithe de type faujasite BaX Structural Characterization of Para- and Meta- Xylene in Bax Zeolite

Directory of Open Access Journals (Sweden)

Mellot C.

2006-11-01

Full Text Available La séparation du para-xylène des isomères aromatiques en C8 est réalisée industriellement grâce à l'adsorption sur tamis moléculaire zéolithique. Une amélioration des propriétés de séparation des tamis, et en particulier de leur sélectivité, nécessite, entre autres, une bonne connaissance des interactions entre les molécules d'adsorbat et la structure zéolithique. Pour ce faire, nous avons fait appel à deux techniques de caractérisation physico-chimique : la diffraction des neutrons et la spectroscopie infrarouge. Nous avons étudié une zéolithe BaX de type faujasite sur laquelle nous avons adsorbé, à l'état de corps purs, les isomères para- et méta- du xylène. Cette zéolithe est connue industriellement pour ses propriétés sélectives performantes pour le paraxylène. Les analyses ont été réalisées en considérant tout d'abord un faible taux de remplissage, voisin d'une molécule par supercage de zéolithe, et ensuite à saturation où la zéolithe contient sensiblement trois molécules par supercage. La diffraction des neutrons permet, à basse température, de localiser les molécules dans la zéolithe et de préciser leur interaction avec le cation Ba²+. La spectroscopie infrarouge permet une étude des caractéristiques vibrationnelles de l'adsorbat en fonction du taux de recouvrement. Une synthèse des résultats obtenus à l'aide de ces deux méthodes d'investigation nous a permis de dégager un modèle de remplissage des supercages pour les deux isomères considérés. Ainsi, des différences significatives sont mises en évidence. En ce qui concerne le para-xylène, pour un taux de remplissage inférieur à deux molécules par supercage, les molécules de para-xylène viennent se positionner au voisinage des cations en site SII de la supercage. La troisième molécule de para-xylène introduite dans la zéolithe n'est pas en interaction avec un cation Ba²+ et sera localisée dans un nouveau site F

The Copenhagen Burnout Inventory: A new tool for the assessment of burnout

DEFF Research Database (Denmark)

Kristensen, Tage S.; Borritz, Marianne; Villadsen, Ebbe

2005-01-01

Burnout; CBI; Copenhagen Burnout Inventory; exhaustion;fatigue; human service work; psychosocial work environment; PUMA study; questionnaire validity......Burnout; CBI; Copenhagen Burnout Inventory; exhaustion;fatigue; human service work; psychosocial work environment; PUMA study; questionnaire validity...

Adidas ja Nike - nina vastu nina / Mikk Salu

Index Scriptorium Estoniae

Salu, Mikk, 1975-

2005-01-01

Spordikaupade tootja Adidas ostab Reeboki 3 miljardi euro eest. Adidase ja Reeboki ühinemisse suhtub skeptiliselt Puma, selle tegevjuht Jochen Zeitz lükkab tagasi kuuldused Nike'i ja Puma võimaliku ühinemise kohta

Evidencias fotográfica, biológica y genética de la presencia actual de jaguaroundi (Puma yagouaroundi en Michoacán, México Photographic, biological and genetic evidences of the presence of jaguaroundi (Puma yagouaroundi at the moment in Michoacán, Mexico

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Tiberio C. Monterrubio-Rico

2012-09-01

Full Text Available El jaguaroundi, a pesar de su amplia distribución neotropical, es uno de los felinos menos estudiados del continente y se carece de estudios genéticos sobre la especie. Para el estado de Michoacán ha existido la sospecha de su presencia y no obstante que sólo se tenía un registro del año 1970, los mapas de distribución de la especie en México incluyen al estado. Combinando métodos de campo (trampas cámara, recolección de campo, transectos y genotipificación molecular, obtuvimos evidencia fotográfica, biológica y genética que confirma la presencia actual de jaguaroundi (Puma yagouaroundi en 3 regiones del estado de Michoacán, México. Se obtuvieron 11 registros fotográficos en 7 localidades con bosque tropical y 7 de estos registros, revelaron que la especie está activa principalmente por la tarde, que existen 2 fases de pelaje, predominando la fase clara y que se reproduce en el estado. Con base en las distancias e independencia entre registros de los municipios de Arteaga y Lázaro Cárdenas, se plantea la hipótesis de que la distribución continúa a lo largo de la sierra Madre del Sur y la costa del Pacífico de Michoacán, aunque se desconoce si hay conectividad hacia la depresión del Balsas. Se obtuvieron 2 secuencias de 1089 y 1096 pb del gen de citocromo b que actualmente son las más largas que se han obtenido para la especie en México y el norte del continente. Las secuencias indican que hay 2 haplotipos distintos. La presencia de la especie en 3 regiones y los 2 haplotipos permiten suponer que en Michoacán puede contar con importante diversidad genética, aunque hace falta ampliar el tamaño de muestra para confirmarlo. Las secuencias obtenidas permitirán la comparación con individuos de otras regiones del país para conocer mejor la variabilidad genética en la especie y auxiliarán en la identificación de poblaciones para conservación.The jaguaroundi is one of the least studied felids on the American

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

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Miaki Uzu

2015-05-01

Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-κB/IκBα, and Bcl-2/Bax signaling

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Wang YY

2015-12-01

Full Text Available Yuanyuan Wang, Rong Wang, Yujie Wang, Ruqin Peng, Yan Wu, Yongfang Yuan Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Background: Liver fibrosis is the consequence of diverse liver injuries and can eventually develop into liver cirrhosis. Ginkgo biloba extract (GBE is an extract from dried ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. Purpose and methods: Aimed to investigate the underlying protective mechanisms of GBE on carbon tetrachloride (CCl4-induced liver fibrosis in rats. Male Sprague Dawley rats were randomly divided into four groups: control group (C, model group (M, low-dose group (L, and high-dose group (H. Liver fibrosis was induced by CCl4 groups M, L, and H: group C was administered saline. In addition, GBE at different doses was used to treat groups L and H. Results: The results of hematoxylin and eosin staining, Masson’s trichrome staining, a liver function index, and a liver fibrosis index showed that GBE application noticeably mitigated fibrosis and improved the function of the liver. The western blotting and immunohistochemistry analyses indicated that GBE reduced liver fibrosis not only by inhibiting p38 MAPK and NF-κBp65 via inhibition of IκBα degradation but also by inhibiting hepatocyte apoptosis via downregulation of Bax, upregulation of Bcl-2, and subsequent inhibition of caspase-3 activation. Inflammation-associated factors and hepatic stellate cell (HSC-activation markers further demonstrated that GBE could effectively inhibit HSC activation and inflammation as a result of its regulation of p38 MAPK and nuclear factor-kappa B/IκBα signaling. Conclusion: Our findings indicated a novel role for GBE in the treatment of liver fibrosis. The potential mechanisms may be associated with the following signaling pathways: 1 the p38 MAPK

Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

Science.gov (United States)

Ebrahimzadeh Bideskan, Alireza; Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Hosseini, Mahmoud; Rajabzadeh, Aliakbar

2017-07-05

The usage of Titanium dioxide nanoparticles (TiO 2 -NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO 2 -NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO 2 -NPs on rat offspring hippocampus during developmental period. Pregnant and lactating Wistar rats received intragastric TiO 2 -NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO 2 -NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO 2 -NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO 2 -NPs group significantly increased and decreased, respectively (P<0.01). These findings provide strong evidence that maternal exposure to TiO 2 -NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and

Values, animal symbolism, and human-animal relationships associated to two threatened felids in Mapuche and Chilean local narratives

Science.gov (United States)

2013-01-01

Background The Chilean temperate rainforest has been subjected to dramatic fragmentation for agriculture and forestry exploitation. Carnivore species are particularly affected by fragmentation and the resulting resource use conflicts with humans. This study aimed at understanding values and human-animal relationships with negatively perceived threatened carnivores through the disclosure of local stories and Mapuche traditional folktales. Methods Our mixed approach comprised the qualitative analysis of 112 stories on the kodkod cat (Leopardus guigna) and the puma (Puma concolor) collected by students (9-14 years) from 28 schools in the Araucania region within their family contexts, 10 qualitative in-depth interviews with indigenous Mapuche people, 35 traditional Mapuche legends, and the significance of naming found in ethnographic collections. Results We revealed a quasi-extinction of traditional tales in the current knowledge pool about pumas and kodkods, local anecdotes, however, were present in significant numbers. Values associated to both felids were manifold, ranging from negativistic to positive values. While pumas played an important role in people’s spirituality, negative mythological connotations persisted in kodkod stories. Four prominent relationships were derived: (1) Both felids represent threats to livestock, pumas even to life, (2) both felids are symbols for upcoming negative events, (3) pumas are spiritual creatures, and (4) kodkods are threatened by humans. Recommendations are provided for stimulating new ways of perceiving unpopular and threatened carnivores among those who live in vicinity to them. PMID:23764186

Primeros registros de 4 especies de felinos en el sur de Puebla, México

OpenAIRE

Farías, Verónica; Téllez, Oswaldo; Botello, Francisco; Hernández, Omar; Berruecos, Jessica; Olivares, Saúl J.; Hernández, Julio C.

2015-01-01

Se presentan los primeros registros de margay (Leopardus wiedii), gato montés (Lynx rufus), puma (Puma concolor) y jaguarundi (Puma yagouaroundi) en el sur del estado de Puebla. El trabajo de campo fue parte de una monitorización participativa que incluyó a las autoridades civiles del ejido. Se colocaron 11 estaciones de cámaras-trampa digitales que funcionaron del 18 de diciembre de 2012 al 18 de febrero de 2014. Con un esfuerzo de muestreo de 2,669 días-trampa y dentro del conjunto de regis...

The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

International Nuclear Information System (INIS)

Gao Jiayu; Morgan, Winston A.; Sanchez-Medina, Alberto; Corcoran, Olivia

2011-01-01

Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G 0 /G 1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells

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Xiaoyan Zhang

2013-05-01

Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

Piceatannol promotes apoptosis via up-regulation of microRNA-129 expression in colorectal cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Zhang, Haogang [Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081 (China); Jia, Ruichun [Department of Blood Transfusion, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081 (China); Wang, Chunjing; Hu, Tianming [Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081 (China); Wang, Fujing, E-mail: wangfujing-hyd@163.com [Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081 (China)

2014-09-26

Highlights: • Piceatannol induces apoptosis in cultured CRC cells. • Piceatannol promotes expression of miR-129. • miR-129 mediates proapoptotic effects of piceatannol. - Abstract: Piceatannol, a naturally occurring analog of resveratrol, has been confirmed as an antitumor agent by inhibiting proliferation, migration, and metastasis in diverse cancer. However, the effect and mechanisms of piceatannol on colorectal cancer (CRC) have not been well understood. This study aimed to test whether piceatannol could inhibit growth of CRC cells and reveal its underlying molecular mechanism. MTT assay was used to detect the cell viability in HCT116 and HT29 cells. Flow cytometry analysis was employed to measure apoptosis of CRC cells. Bcl-2, Bax and caspase-3 levels were analyzed by Western blot and miR-129 levels were determined by real-time RT-PCR. Our study showed that piceatannol inhibited HCT116 and HT29 cells growth in a concentration- and time-dependent manner. Piceatannol induced apoptosis by promoting expression of miR-129, and then inhibiting expression of Bcl-2, an known target for miR-129. Moreover, knock down of miR-129 could reverse the reduction of cell viability induced by piceatannol in HCT116 and HT29 cells. Taken together, our study unraveled the ability of piceatannol to suppress colorectal cancer growth and elucidated the participation of miR-129 in the anti-cancer action of piceatannol. Our findings suggest that piceatannol can be considered to be a promising anticancer agent for CRC.

Canine Distemper Virus in Wild Felids of Costa Rica.

Science.gov (United States)

Avendaño, Roberto; Barrueta, Flor; Soto-Fournier, Sofía; Chavarría, Max; Monge, Otto; Gutiérrez-Espeleta, Gustavo A; Chaves, Andrea

2016-04-28

Several highly infectious diseases can be transmitted through feces and cause elevated mortality among carnivore species. One such infectious agent, canine distemper virus (CDV; Paramyxoviridae: Morbillivirus), has been reported to affect wild carnivores, among them several felid species. We screened free-ranging and captive wild carnivores in Costa Rica for CDV. Between 2006 and 2012, we collected 306 fecal samples from 70 jaguars (Panther onca), 71 ocelots ( Leopardus pardalis ), five jaguarundis (Puma yaguaroundi), 105 pumas ( Puma concolor ), five margays ( Leopardus wiedii ), 23 coyotes ( Canis latrans ), and 27 undetermined Leopardus spp. We found CDV in six individuals: one captive jaguarundi (rescued in 2009), three free-ranging ocelots (samples collected in 2012), and two free-ranging pumas (samples collected in 2007). Phylogenetic analyses were performed using sequences of the phosphoprotein (P) gene. We provide evidence of CDV in wild carnivores in Costa Rica and sequence data from a Costa Rican CDV isolate, adding to the very few sequence data available for CDV isolates from wild Central American carnivores.

Differences Between Distributed and Parallel Systems

Energy Technology Data Exchange (ETDEWEB)

Brightwell, R.; Maccabe, A.B.; Rissen, R.

1998-10-01

Distributed systems have been studied for twenty years and are now coming into wider use as fast networks and powerful workstations become more readily available. In many respects a massively parallel computer resembles a network of workstations and it is tempting to port a distributed operating system to such a machine. However, there are significant differences between these two environments and a parallel operating system is needed to get the best performance out of a massively parallel system. This report characterizes the differences between distributed systems, networks of workstations, and massively parallel systems and analyzes the impact of these differences on operating system design. In the second part of the report, we introduce Puma, an operating system specifically developed for massively parallel systems. We describe Puma portals, the basic building blocks for message passing paradigms implemented on top of Puma, and show how the differences observed in the first part of the report have influenced the design and implementation of Puma.

Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

Directory of Open Access Journals (Sweden)

Sushma Kalmodia

2017-12-01

Full Text Available Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB. Nanoparticle-based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNPs to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in GNP-HDM2-treated cells by qRT-PCR and western blotting revealed that the p53 protein was upregulated; however, transactivation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of GNP-HDM2-treated cells suggested that upregulation of p53 might presumptively mediate apoptosis through the induction of p53-inducible miRNAs.

Structural and ferroelectric properties of Sr1−xBaxBi2Nb2O9 thin films obtained by dip-coating

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Y. González-Abreu

2017-10-01

Full Text Available The paper presents the structural and ferroelectric results for Sr1−xBaxBi2Nb2O9(x=0.30; 0.85 thin films, which were obtained by using dip-coating. The solutions containing the desirable ions were prepared from the powders of the previous studied ceramic samples. The films were deposited at room temperature on Fluorine-doped Tin Oxide (FTO substrates and submitted to a heat treatment for crystallization. The films were characterized by using scanning microscopy electronic, energy dispersive spectroscopy and ellipsometry. Hysteresis ferroelectric loops were obtained, at room temperature, by using a Sawyer-Tower circuit at several frequencies. A well-defined grain structure was observed for both compositions. The energy dispersive spectroscopy (EDS measurements revealed the presence of the corresponding elements from the chemical composition of the ceramic systems. The band-gap energy was around 3.3eV for both samples. Typical hysteresis loops for normal and relaxor ferroelectrics were obtained for x=0.30 and 0.85, respectively.

Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays

International Nuclear Information System (INIS)

Chi, C.; Hayashi, Daisuke; Nemoto, Masato; Nyui, Minako; Anzai, Kazunori; Urano, Shiro

2011-01-01

We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation. (author)

Evolutionary and functional mitogenomics associated with the genetic restoration of the Florida panther

Science.gov (United States)

Ochoa, Alexander; Onorato, David P.; Fitak, Robert R.; Roelke-Parker, Melody; Culver, Melanie

2017-01-01

Florida panthers are endangered pumas that currently persist in reduced patches of habitat in South Florida, USA. We performed mitogenome reference-based assemblies for most parental lines of the admixed Florida panthers that resulted from the introduction of female Texas pumas into South Florida in 1995. With the addition of 2 puma mitogenomes, we characterized 174 single nucleotide polymorphisms (SNPs) across 12 individuals. We defined 5 haplotypes (Pco1–Pco5), one of which (Pco1) had a geographic origin exclusive to Costa Rica and Panama and was possibly introduced into the Everglades National Park, Florida, prior to 1995. Haplotype Pco2 was native to Florida. Haplotypes Pco3 and Pco4 were exclusive to Texas, whereas haplotype Pco5 had an undetermined geographic origin. Phylogenetic inference suggests that haplotypes Pco1–Pco4 diverged ~202000 (95% HPDI = 83000–345000) years ago and that haplotypes Pco2–Pco4 diverged ~61000 (95% HPDI = 9000–127000) years ago. These results are congruent with a south-to-north continental expansion and with a recent North American colonization by pumas. Furthermore, pumas may have migrated from Texas to Florida no earlier than ~44000 (95% HPDI = 2000–98000) years ago. Synonymous mutations presented a greater mean substitution rate than other mitochondrial functional regions: nonsynonymous mutations, tRNAs, rRNAs, and control region. Similarly, all protein-coding genes were under predominant negative selection constraints. We directly and indirectly assessed the presence of potential deleterious SNPs in the ND2 and ND5 genes in Florida panthers prior to and as a consequence of the introduction of Texas pumas. Screenings for such variants are recommended in extant Florida panthers.

Particulate barium tracing of significant mesopelagic carbon remineralisation in the North Atlantic

Science.gov (United States)

Lemaitre, Nolwenn; Planquette, Hélène; Planchon, Frédéric; Sarthou, Géraldine; Jacquet, Stéphanie; García-Ibáñez, Maribel I.; Gourain, Arthur; Cheize, Marie; Monin, Laurence; André, Luc; Laha, Priya; Terryn, Herman; Dehairs, Frank

2018-04-01

The remineralisation of sinking particles by prokaryotic heterotrophic activity is important for controlling oceanic carbon sequestration. Here, we report mesopelagic particulate organic carbon (POC) remineralisation fluxes in the North Atlantic along the GEOTRACES-GA01 section (GEOVIDE cruise; May-June 2014) using the particulate biogenic barium (excess barium; Baxs) proxy. Important mesopelagic (100-1000 m) Baxs differences were observed along the transect depending on the intensity of past blooms, the phytoplankton community structure, and the physical forcing, including downwelling. The subpolar province was characterized by the highest mesopelagic Baxs content (up to 727 pmol L-1), which was attributed to an intense bloom averaging 6 mg chl a m-3 between January and June 2014 and by an intense 1500 m deep convection in the central Labrador Sea during the winter preceding the sampling. This downwelling could have promoted a deepening of the prokaryotic heterotrophic activity, increasing the Baxs content. In comparison, the temperate province, characterized by the lowest Baxs content (391 pmol L-1), was sampled during the bloom period and phytoplankton appear to be dominated by small and calcifying species, such as coccolithophorids. The Baxs content, related to oxygen consumption, was converted into a remineralisation flux using an updated relationship, proposed for the first time in the North Atlantic. The estimated fluxes were of the same order of magnitude as other fluxes obtained using independent methods (moored sediment traps, incubations) in the North Atlantic. Interestingly, in the subpolar and subtropical provinces, mesopelagic POC remineralisation fluxes (up to 13 and 4.6 mmol C m-2 d-1, respectively) were equalling and occasionally even exceeding upper-ocean POC export fluxes, deduced using the 234Th method. These results highlight the important impact of the mesopelagic remineralisation on the biological carbon pump of the studied area with a near

Direct effect of curcumin on porcine ovarian cell functions.

Science.gov (United States)

Kádasi, Attila; Maruniaková, Nora; Štochmaľová, Aneta; Bauer, Miroslav; Grossmann, Roland; Harrath, Abdel Halim; Kolesárová, Adriana; Sirotkin, Alexander V

2017-07-01

Curcuma longa Linn (L.) is a plant widely used in cooking (in curry powder a.o.) and in folk medicine, but its action on reproductive processes and its possible mechanisms of action remain to be investigated. The objective of this study was to examine the direct effects of curcumin, the major Curcuma longa L. molecule, on basic ovarian cell functions such as proliferation, apoptosis, viability and steroidogenesis. Porcine ovarian granulosa cells were cultured with and without curcumin (at doses of 0, 1, 10 and 100μg/ml of medium). Markers of proliferation (accumulation of PCNA) and apoptosis (accumulation of bax) were analyzed by immunocytochemistry. The expression of mRNA for PCNA and bax was detected by RT-PCR. Cell viability was detected by trypan blue exclusion test. Release of steroid hormones (progesterone and testosterone) was measured by enzyme immunoassay (EIA). It was observed that addition of curcumin reduced ovarian cell proliferation (expression of both PCNA and its mRNA), promoted apoptosis (accumulation of both bax and its mRNA), reduced cell viability, and stimulated both progesterone and testosterone release. These observations demonstrate the direct suppressive effect of Curcuma longa L./curcumin on female gonads via multiple mechanisms of action - suppression of ovarian cell proliferation and viability, promotion of their apoptosis (at the level of mRNA transcription and subsequent accumulation of promoters of genes regulating these activities) and release of anti-proliferative and pro-apoptotic progesterone and androgen. The potential anti-gonadal action of curcumin should be taken into account by consumers of Curcuma longa L.-containing products. Copyright © 2017 Elsevier B.V. All rights reserved.

The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading

Directory of Open Access Journals (Sweden)

Anna Baulies

2018-04-01

Full Text Available Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC, by depleting mitochondrial GSH (mGSH due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC and SLC25A11 (2-oxoglutarate carrier, OGC have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment. Keywords: Cholesterol

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

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Sarah A. Abd El-Aal

2017-10-01

Full Text Available Statins were reported to lower the Coenzyme Q10 (CoQ10 content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg, CoQ10 (10 mg/kg and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.

Modeling connectivity to identify current and future anthropogenic barriers to movement of large carnivores: A case study in the American Southwest.

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McClure, Meredith L; Dickson, Brett G; Nicholson, Kerry L

2017-06-01

This study sought to identify critical areas for puma ( Puma concolor ) movement across the state of Arizona in the American Southwest and to identify those most likely to be impacted by current and future human land uses, particularly expanding urban development and associated increases in traffic volume. Human populations in this region are expanding rapidly, with the potential for urban centers and busy roads to increasingly act as barriers to demographic and genetic connectivity of large-bodied, wide-ranging carnivores such as pumas, whose long-distance movements are likely to bring them into contact with human land uses and whose low tolerance both for and from humans may put them at risk unless opportunities for safe passage through or around human-modified landscapes are present. Brownian bridge movement models based on global positioning system collar data collected during bouts of active movement and linear mixed models were used to model habitat quality for puma movement; then, a wall-to-wall application of circuit theory models was used to produce a continuous statewide estimate of connectivity for puma movement and to identify pinch points, or bottlenecks, that may be most at risk of impacts from current and future traffic volume and expanding development. Rugged, shrub- and scrub-dominated regions were highlighted as those offering high quality movement habitat for pumas, and pinch points with the greatest potential impacts from expanding development and traffic, although widely distributed, were particularly prominent to the north and east of the city of Phoenix and along interstate highways in the western portion of the state. These pinch points likely constitute important conservation opportunities, where barriers to movement may cause disproportionate loss of connectivity, but also where actions such as placement of wildlife crossing structures or conservation easements could enhance connectivity and prevent detrimental impacts before they occur.

Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate-induced apoptotic cell death.

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Marie Lue Antony

Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, decreases viability of cancer cells by causing apoptosis but the mechanism of cell death is not fully understood. The present study was undertaken to determine the role of Bcl-2 family proteins in BITC-induced apoptosis using MDA-MB-231 (breast, MCF-7 (breast, and HCT-116 (colon human cancer cells. The B-cell lymphoma 2 interacting mediator of cell death (Bim protein was dispensable for proapoptotic response to BITC in MCF-7 and MDA-MB-231 cells as judged by RNA interference studies. Instead, the BITC-treated MCF-7 and MDA-MB-231 cells exhibited upregulation of p53 upregulated modulator of apoptosis (PUMA protein. The BITC-mediated induction of PUMA was relatively more pronounced in MCF-7 cells due to the presence of wild-type p53 compared with MDA-MB-231 with mutant p53. The BITC-induced apoptosis was partially but significantly attenuated by RNA interference of PUMA in MCF-7 cells. The PUMA knockout variant of HCT-116 cells exhibited significant resistance towards BITC-induced apoptosis compared with wild-type HCT-116 cells. Attenuation of BITC-induced apoptosis in PUMA knockout HCT-116 cells was accompanied by enhanced G2/M phase cell cycle arrest due to induction of p21 and down regulation of cyclin-dependent kinase 1 protein. The BITC treatment caused a decrease in protein levels of Bcl-xL (MCF-7 and MDA-MB-231 cells and Bcl-2 (MCF-7 cells. Ectopic expression of Bcl-xL in MCF-7 and MDA-MB-231 cells and that of Bcl-2 in MCF-7 cells conferred protection against proapoptotic response to BITC. Interestingly, the BITC-treated MDA-MB-231 cells exhibited induction of Bcl-2 protein expression, and RNA interference of Bcl-2 in this cell line resulted in augmentation of BITC-induced apoptosis. The BITC-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with the induction of PUMA protein in the tumor. In conclusion, the results of the present study

Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.

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Kangkai Wang

Full Text Available Mipu1 (myocardial ischemic preconditioning up-regulated protein 1, recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2 treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.

Ocelot Population Status in Protected Brazilian Atlantic Forest.

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Massara, Rodrigo Lima; Paschoal, Ana Maria de Oliveira; Doherty, Paul Francis; Hirsch, André; Chiarello, Adriano Garcia

2015-01-01

Forest fragmentation and habitat loss are detrimental to top carnivores, such as jaguars (Panthera onca) and pumas (Puma concolor), but effects on mesocarnivores, such as ocelots (Leopardus pardalis), are less clear. Ocelots need native forests, but also might benefit from the local extirpation of larger cats such as pumas and jaguars through mesopredator release. We used a standardized camera trap protocol to assess ocelot populations in six protected areas of the Atlantic forest in southeastern Brazil where over 80% of forest remnants are forest cover, number of free-ranging domestic dogs and presence of top predators. Ocelot abundance was positively correlated with reserve size and the presence of top predators (jaguar and pumas) and negatively correlated with the number of dogs. We also found higher detection probabilities in less forested areas as compared to larger, intact forests. We suspect that smaller home ranges and higher movement rates in smaller, more degraded areas increased detection. Our data do not support the hypothesis of mesopredator release. Rather, our findings indicate that ocelots respond negatively to habitat loss, and thrive in large protected areas inhabited by top predators.

Valproic Acid Promotes Survival of Facial Motor Neurons in Adult Rats After Facial Nerve Transection: a Pilot Study.

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Zhang, Lili; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Liu, Wenwen; Bai, Xiaohui; Zhou, Meijuan; Li, Jianfeng; Wang, Haibo

2018-04-01

Valproic acid (VPA), a medication primarily used to treat epilepsy and bipolar disorder, has been applied to the repair of central and peripheral nervous system injury. The present study investigated the effect of VPA on functional recovery, survival of facial motor neurons (FMNs), and expression of proteins in rats after facial nerve trunk transection by functional measurement, Nissl staining, TUNEL, immunofluorescence, and Western blot. Following facial nerve injury, all rats in group VPA showed a better functional recovery, which was significant at the given time, compared with group NS. The Nissl staining results demonstrated that the number of FMNs survival in group VPA was higher than that in group normal saline (NS). TUNEL staining showed that axonal injury of facial nerve could lead to neuronal apoptosis of FMNs. But treatment of VPA significantly reduced cell apoptosis by decreasing the expression of Bax protein and increased neuronal survival by upregulating the level of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) expression in injured FMNs compared with group NS. Overall, our findings suggest that VPA may advance functional recovery, reduce lesion-induced apoptosis, and promote neuron survival after facial nerve transection in rats. This study provides an experimental evidence for better understanding the mechanism of injury and repair of peripheral facial paralysis.

Social interactions in a solitary carnivore

Institute of Scientific and Technical Information of China (English)

L.Mark ELBROCH; Howard QUIGLEY

2017-01-01

In total,177 of 245 terrestrial carnivores are described as solitary,and much of carnivore ecology is built on the assumptions that interactions between adult solitary carnivores are rare.We employed Global Positioning System (GPS) technology and motion-triggered cameras to test predictions of land-tenure territoriality and the resource dispersion hypothesis in a territorial carnivore,the puma Puma concolor.We documented 89 independent GPS interactions,60％ of which occurred at puma kills (n=53),59 camera interactions,11 (17％) of which captured courtship behaviors,and 5 other interactions (1 F-F,3 M-F,and 1 M-M).Mean minimum weekly contact rates were 5.5 times higher in winter,the season when elk Cervus elaphus were aggregated at lower elevations and during which puma courtship primarily occurred.In winter,contacts rates were 0.6± 0.3 (standard deviation (SD)) interactions/week vs.0.1 ± 0.1 (SD) interactions/week during summer.The preponderance of interactions at food sources supported the resource dispersion hypothesis,which predicts that resource fluxes can explain temporary social behaviors that do not result in any apparent benefits for the individuals involved.Conspecific tolerance is logical when a prey is so large that the predator that killed it cannot consume it entirely,and thus,the costs of tolerating a conspecific sharing the kill are less than the potential costs associated with defending it and being injured.Puma aggregations at kills numbered as high as 9,emphasizing the need for future research on what explains tolerance among solitary carnivores.

Composition-control of magnetron-sputter-deposited (BaxSr1-x)Ti1+yO3+z thin films for voltage tunable devices

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Im, Jaemo; Auciello, O.; Baumann, P. K.; Streiffer, S. K.; Kaufman, D. Y.; Krauss, A. R.

2000-01-01

Precise control of composition and microstructure is critical for the production of (BaxSr1-x)Ti1+yO3+z (BST) dielectric thin films with the large dependence of permittivity on electric field, low losses, and high electrical breakdown fields that are required for successful integration of BST into tunable high-frequency devices. Here, we present results on composition-microstructure-electrical property relationships for polycrystalline BST films produced by magnetron-sputter deposition, that are appropriate for microwave and millimeter-wave applications such as varactors and frequency triplers. Films with controlled compositions were grown from a stoichiometric Ba0.5Sr0.5TiO3 target by control of the background processing gas pressure. It was determined that the (Ba+Sr)/Ti ratios of these BST films could be adjusted from 0.73 to 0.98 by changing the total (Ar+O2) process pressure, while the O2/Ar ratio did not strongly affect the metal ion composition. Film crystalline structure and dielectric properties as a function of the (Ba+Sr)/Ti ratio are discussed. Optimized BST films yielded capacitors with low dielectric losses (0.0047), among the best reported for sputtered BST, while still maintaining tunabilities suitable for device applications.

[Baicalein promotes the apoptosis of HeLa cells by inhibiting ERK1/2 expression].

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Wang, Yongzhou; Xia, Jiyi; Tang, Xiaoping; Tang, Li; Mao, Xiguang; Zhang, Yujiao; Yu, Xiaolan

2016-11-01

Objective To investigate the effects of baicalein and U0126 treatment on the apoptosis of human cervical carcinoma HeLa cells and the potential mechanism. Methods HeLa cells were subjected to (1, 2, 5, 10, 20, 50, 100, 200, 300) μmol/L baicalein or (1, 2, 5, 10, 20, 30) μmol/L U0126 treatment for 24 hours. The optimal concentrations of baicalein and U0126 for HeLa inhibition was determined by a cell counting Kit-8 assay. HeLa cells were then treated with these inhibitory concentrations for 24 hours separately or in combination. The cell cycle and the degree of apoptosis were analyzed by flow cytometry. The cell apoptosis index was evaluated by the TUNEL assay. The expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), Bax, and Bcl-2 at the mRNA and protein levels were examined by real-time PCR and Western blotting, respectively. Results Optimal inhibitory concentrations of baicalein and U0126 for HeLa cells were 200 μmol/L and 10 μmol/L, respectively. Compared with the control group, baicalein treatment increased the growth rate of cells in the G0/G1 phase but decreased the S phase. Combination treatment of 200 μmol/L baicalein and 10 μmol/L U0126 for 24 hours further reduced the S phase growth rate. Treatment with 10 μmol/L U0126 or 200 μmol/L baicalein for 24 hours induced cell apoptosis, and the combination treatment induced more apoptosis. Treatment by baicalein alone or in combination with U0126 for 24 hours significantly decreased ERK1/2 and Bcl-2 mRNA expressions, and upregulated Bax mRNA expression. It also downregulated ERK1/2 phosphorylation and Bcl-2 protein expression, while increasing Bax protein expression. Conclusion Both baicalein and U012 appear to inhibit proliferation, induce apoptosis, and increase the growth rate in the G0/G1 phase but reduce the S phase of HeLa cells. This effect is enhanced when they are used synergistically.

Bax/Bcl-2 protein expression ratio and leukocyte function are related to reduction of Walker-256 tumor growth after β-hydroxy-β-methylbutyrate (HMB) administration in Wistar rats.

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Kuczera, Diogo; Paro de Oliveira, Heloísa Helena; Fonseca Guimarães, Fernando de Souza; de Lima, Carina; Alves, Luciana; Machado, Andressa Franzói; Coelho, Isabela; Yamaguchi, Adriana; Donatti, Lucélia; Naliwaiko, Katya; Fernandes, Luiz Claudio; Nunes, Everson Araújo

2012-01-01

This study investigated the mechanisms by which β-hydroxy-β-methylbutyrate (HMB) administration in rats reduces Walker-256 tumor growth. Male Wistar rats were supplemented with HMB (76 mg/kg/day) (HW), or a placebo (W), during 8 wk by gavage. At the 6th wk, rats were inoculated with a suspension of Walker 256 tumor cells (3 × 10(7)/mL). Fifteen days after inoculation, the HW group showed higher glycemia (109.4 ± 5.53 vs. 89.87 ± 7.02 mg/dL, P HMB-treated rats displayed a 36.9% decrement in rates of proliferation ex vivo and a significant increase in the Bax/Bcl-2 protein expression ratio in comparison to those extracted from the placebo-treated rats (P HMB supplementation decreases tumor burden by modifying the inner environment of tumor cells and by interfering with blood leukocyte function.

Princeton University Materials Academy for underrepresented students

Science.gov (United States)

Steinberg, Daniel; Rodriguez Martinez, Sara; Cody, Linda

Summer 2016 gave underrepresented high school students from Trenton New Jersey the opportunity to learn materials science, sustainability and the physics and chemistry of energy storage from Princeton University professors. New efforts to place this curriculum online so that teachers across the United States can teach materials science as a tool to teach ``real'' interdisciplinary science and meet the new Next Generation Science Standards (NGSS). The Princeton University Materials Academy (PUMA) is an education outreach program for underrepresented high school students. It is part of the Princeton Center for Complex Materials (PCCM), a National Science Foundation (NSF) funded Materials Research Engineering and Science Center (MRSEC). PUMA has been serving the community of Trenton New Jersey which is only eight miles from the Princeton University campus. We reached over 250 students from 2003-2016 with many students repeating for multiple years. 100% of our PUMA students have graduated high school and 98% have gone on for college. This is compared with overall Trenton district graduation rate of 48% and a free and reduced lunch of 83%. We discuss initiatives to share the curriculum online to enhance the reach of PCCM' PUMA and to help teachers use materials science to meet NGSS and give their students opportunities to learn interdisciplinary science. MRSEC, NSF (DMR-1420541).

Ocelot Population Status in Protected Brazilian Atlantic Forest.

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Rodrigo Lima Massara

Full Text Available Forest fragmentation and habitat loss are detrimental to top carnivores, such as jaguars (Panthera onca and pumas (Puma concolor, but effects on mesocarnivores, such as ocelots (Leopardus pardalis, are less clear. Ocelots need native forests, but also might benefit from the local extirpation of larger cats such as pumas and jaguars through mesopredator release. We used a standardized camera trap protocol to assess ocelot populations in six protected areas of the Atlantic forest in southeastern Brazil where over 80% of forest remnants are < 50 ha. We tested whether variation in ocelot abundance could be explained by reserve size, forest cover, number of free-ranging domestic dogs and presence of top predators. Ocelot abundance was positively correlated with reserve size and the presence of top predators (jaguar and pumas and negatively correlated with the number of dogs. We also found higher detection probabilities in less forested areas as compared to larger, intact forests. We suspect that smaller home ranges and higher movement rates in smaller, more degraded areas increased detection. Our data do not support the hypothesis of mesopredator release. Rather, our findings indicate that ocelots respond negatively to habitat loss, and thrive in large protected areas inhabited by top predators.

Involvement of Bax and Bcl-2 in Induction of Apoptosis by Essential Oils of Three Lebanese Salvia Species in Human Prostate Cancer Cells

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Alessandra Russo

2018-01-01

Full Text Available Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145. The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl2,5-diphenyl-tetrazolium bromide (MTT test and lactate dehydrogenase (LDH release was used to quantify necrosis cell death. Genomic DNA, caspase-3 activity, expression of cleaved caspase-9, B-cell lymphoma 2 (Bcl-2 and Bcl-2 associated X (Bax proteins were analyzed in order to study the apoptotic process. The role of reactive oxygen species in cell death was also investigated. We found that the three essential oils, containing caryophyllene oxide as a main constituent, are capable of reducing the growth of human prostate cancer cells, activating an apoptotic process and increasing reactive oxygen species generation. These results suggest it could be profitable to further investigate the effects of these essential oils for their possible use as anticancer agents in prostate cancer, alone or in combination with chemotherapy agents.

A design for the control of apoptosis in genetically modified Saccharomyces cerevisiae.

Science.gov (United States)

Nishida, Nao; Noguchi, Misa; Kuroda, Kouichi; Ueda, Mitsuyoshi

2014-01-01

We have engineered a system that holds potential for use as a safety switch in genetically modified yeasts. Human apoptotic factor BAX (no homolog in yeast), under the control of the FBP1 (gluconeogenesis enzyme) promoter, was conditionally expressed to induce yeast cell apoptosis after glucose depletion. Such systems might prove useful for the safe use of genetically modified organisms.

Development of a facility using robotics for testing automation of inertial instruments

Science.gov (United States)

Greig, Joy Y.; Lamont, Gary B.; Biezad, Daniel J.; Lewantowicz, Zdsislaw H.; Greig, Joy Y.

1987-01-01

The Integrated Robotics System Simulation (ROBSIM) was used to evaluate the performance of the PUMA 560 arm as applied to testing of inertial sensors. Results of this effort were used in the design and development of a feasibility test environment using a PUMA 560 arm. The implemented facility demonstrated the ability to perform conventional static inertial instrument tests (rotation and tumble). The facility included an efficient data acquisitions capability along with a precision test servomechanism function resulting in various data presentations which are included in the paper. Analysis of inertial instrument testing accuracy, repeatability and noise characteristics are provided for the PUMA 560 as well as for other possible commercial arm configurations. Another integral aspect of the effort was an in-depth economic analysis and comparison of robot arm testing versus use of contemporary precision test equipment.

Exposure of Free-Ranging Wild Carnivores and Domestic Dogs to Canine Distemper Virus and Parvovirus in the Cerrado of Central Brazil.

Science.gov (United States)

Furtado, Mariana Malzoni; Hayashi, Erika Midori Kida; Allendorf, Susan Dora; Coelho, Claudio José; de Almeida Jácomo, Anah Tereza; Megid, Jane; Ramos Filho, José Domingues; Silveira, Leandro; Tôrres, Natália Mundim; Ferreira Neto, José Soares

2016-09-01

Human population growth around protected areas increases the contact between wild and domestic animals, promoting disease transmission between them. This study investigates the exposure of free-ranging wild carnivores and domestic dogs to canine distemper virus (CDV) and parvovirus in Emas National Park (ENP) in the Cerrado savanna of central Brazil. Serum samples were collected from 169 wild carnivores, including the maned wolf (Chrysocyon brachyurus), crab-eating fox (Cerdocyon thous), hoary fox (Pseudalopex vetulus), puma (Puma concolor), ocelot (Leopardus pardalis), pampas cat (Leopardus colocolo), jaguarundi (Herpailurus yagouaroundi), striped hog-nosed skunk (Conepatus semistriatus) and coati (Nasua nasua), and from 35 domestic dogs living on rural properties bordering ENP. Serological tests showed that 10.6% of wild carnivores (maned wolves, crab-eating foxes and ocelots) and 71.4% of domestic dogs were exposed to CDV, and 56.8% of wild carnivores, including all species sampled except coatis, and 57.1% of domestic dogs were exposed to parvovirus. This report is the first to indicate that the free-ranging pampas cat, jaguarundi and striped hog-nosed skunk are exposed to parvovirus. CDV and parvovirus deserve attention in ENP, and it is extremely important to monitor the health of carnivore populations and perform molecular diagnosis of the viruses to determine the possible involvement of the domestic dog in their transmission.

Tubeimoside-1 induces glioma apoptosis through regulation of Bax/Bcl-2 and the ROS/Cytochrome C/Caspase-3 pathway

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Jia G

2015-01-01

Full Text Available Geng Jia,1,* Qiang Wang,2,* Rong Wang,2,* Danni Deng,2 Lian Xue,2 Naiyuan Shao,1 Yi Zhang,1 Xiwei Xia,1 Feng Zhi,2 Yilin Yang1,2 1Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China; 2Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China * These authors contributed equally to this workBackground: Tubeimoside-1 (TBMS1 is a natural compound isolated from tubeimoside, which has been widely used as a traditional Chinese herbal medicine. The purpose of the present study is to investigate the anti-tumor effect and the underling mechanism of TBMS1 on glioma cancer cells.Methods: The MTT assay was performed to evaluate the effect of TBMS1 on glioma cell proliferation. The fluorescent microscopy and flow cytometry analysis were performed to evaluate the effect of TBMS1 on glioma cell apoptosis. The Western blot analysis was used to evaluate the protein change.Results: TBMS1 inhibited glioma cancer cell proliferation in a dose- and time-dependent manner. Fluorescent microscopy and flow cytometry analysis demonstrated that TBMS1 induced glioma cell apoptosis in a concentration-dependent manner. Western blotting showed that TBMS1 induced apoptosis by increasing the expression of Bax and downregulating the level of Bcl-2. Furthermore, we found that TBMS1 induced apoptosis by increasing the concentration of reactive oxygen species through the release of Cytochrome C and activation of Caspase-3.Conclusion: These findings indicate that TBMS1 may be developed as a possible therapeutic agent for the management of glioma. Keywords: Tubeimoside-1, glioma, proliferation, apoptosis

What do health-promoting schools promote?

DEFF Research Database (Denmark)

Simovska, Venka

2012-01-01

-promotion interventions. Directly or indirectly the articles reiterate the idea that health promotion in schools needs to be linked with the core task of the school – education, and to the values inherent to education, such as inclusion, democracy, participation and influence, critical literacy and action competence......Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

Science.gov (United States)

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

Pathogen exposure varies widely among sympatric populations of wild and domestic felids across the United States.

Science.gov (United States)

Carver, Scott; Bevins, Sarah N; Lappin, Michael R; Boydston, Erin E; Lyren, Lisa M; Alldredge, Mathew; Logan, Kenneth A; Sweanor, Linda L; Riley, Seth P D; Serieys, Laurel E K; Fisher, Robert N; Vickers, T Winston; Boyce, Walter; Mcbride, Roy; Cunningham, Mark C; Jennings, Megan; Lewis, Jesse; Lunn, Tamika; Crooks, Kevin R; Vandewoude, Sue

2016-03-01

Understanding how landscape, host, and pathogen traits contribute to disease exposure requires systematic evaluations of pathogens within and among host species and geographic regions. The relative importance of these attributes is critical for management of wildlife and mitigating domestic animal and human disease, particularly given rapid ecological changes, such as urbanization. We screened > 1000 samples from sympatric populations of puma (Puma concolor), bobcat (Lynx rufus), and domestic cat (Felis catus) across urban gradients in six sites, representing three regions, in North America for exposure to a representative suite of bacterial, protozoal, and viral pathogens (Bartonella sp., Toxoplasma gondii, feline herpesvirus-1, feline panleukopenea virus, feline calicivirus, and feline immunodeficiency virus). We evaluated prevalence within each species, and examined host trait and land cover determinants of exposure; providing an unprecedented analysis of factors relating to potential for infections in domesticated and wild felids. Prevalence differed among host species (highest for puma and lowest for domestic cat) and was greater for indirectly transmitted pathogens. Sex was inconsistently predictive of exposure to directly transmitted pathogens only, and age infrequently predictive of both direct and indirectly transmitted pathogens. Determinants of pathogen exposure were widely divergent between the wild felid species. For puma, suburban land use predicted increased exposure to Bartonella sp. in southern California, and FHV-1 exposure increased near urban edges in Florida. This may suggest interspecific transmission with domestic cats via flea vectors (California) and direct contact (Florida) around urban boundaries. Bobcats captured near urban areas had increased exposure to T. gondii in Florida, suggesting an urban source of prey Bobcats captured near urban areas in Colorado and Florida had higher FIV exposure, possibly suggesting increased intraspecific

Experimental investigation of void distribution in Suppression Pool during the initial blowdown period of a Loss of Coolant Accident using air–water two-phase mixture

International Nuclear Information System (INIS)

Rassame, Somboon; Griffiths, Matthew; Yang, Jun; Lee, Doo Yong; Ju, Peng; Choi, Sung Won; Hibiki, Takashi; Ishii, Mamoru

2014-01-01

Highlights: • Basic understanding of the venting phenomena in the SP during a LOCA was obtained. • A series of experiment is carried out using the PUMA-E test facility. • Two phases of experiments, namely, an initial and a quasi-steady phase were observed. • The maximum void penetration depth was experienced during the initial phase. - Abstract: During the initial blowdown period of a Loss of Coolant Accident (LOCA), the non-condensable gas initially contained in the BWR containment is discharged to the pressure suppression chamber through the blowdown pipes. The performance of Emergency Core Cooling System (ECCS) can be degraded due to the released gas ingestion into the suction intakes of the ECCS pumps. The understanding of the relevant phenomena in the pressure suppression chamber is important in analyzing potential gas intrusion into the suction intakes of ECCS pumps. To obtain the basic understanding of the relevant phenomena and the generic data of void distribution in the pressure suppression chamber during the initial blowdown period of a LOCA, tests with various blowdown conditions were conducted using the existing Suppression Pool (SP) tank of the integral test facility, called Purdue University Multi-Dimensional Integral Test Assembly for ESBWR applications (PUMA-E) facility, a scaled downcomer pipe installed in the PUMA-E SP, and air discharge pipe system. Two different diameter sizes of air injection pipe (0.076 and 0.102 m), a range of air volumetric flux (7.9–24.7 m/s), initial void conditions in an air injection pipe (fully void, partially void, and fully filled with water) and different air velocity ramp rates (1.0, 1.5, and 2.0 s) are used to investigate the impact of the blowdown conditions to the void distribution in the SP. Two distinct phases of experiments, namely, an initial and a quasi-steady phase were observed. The maximum void penetration depth was experienced during the initial phase. The quasi-steady phase provided less void

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

Energy Technology Data Exchange (ETDEWEB)

Eid, Rawan [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Boucher, Eric [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Gharib, Nada [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Khoury, Chamel [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Arab, Nagla T.T. [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Murray, Alistair [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Young, Paul G. [Department of Biology, Queen' s University, Kingston, Ontario (Canada); Mandato, Craig A. [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Greenwood, Michael T., E-mail: michael.greenwood@rmc.ca [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada)

2016-03-01

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast. �

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Eid, Rawan; Boucher, Eric; Gharib, Nada; Khoury, Chamel; Arab, Nagla T.T.; Murray, Alistair; Young, Paul G.; Mandato, Craig A.; Greenwood, Michael T.

2016-01-01

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast. �

Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

Science.gov (United States)

Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

2017-03-01

Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which

The Wheat Bax Inhibitor-1 Protein Interacts with an Aquaporin TaPIP1 and Enhances Disease Resistance in Arabidopsis

Directory of Open Access Journals (Sweden)

Pan-Pan Lu

2018-01-01

Full Text Available Bax inhibitor-1 (BI-1 is an endoplasmic reticulum (ER-resident cell death suppressor evolutionarily conserved in eukaryotes. The ability of BI-1 to inhibit the biotic and abiotic stresses have been well-studied in Arabidopsis, while the functions of wheat BI-1 are largely unknown. In this study, the wheat BI-1 gene TaBI-1.1 was isolated by an RNA-seq analysis of Fusarium graminearum (Fg-treated wheat. TaBI-1.1 expression was induced by a salicylic acid (SA treatment and down-regulated by an abscisic acid (ABA treatment. Based on β-glucuronidase (GUS staining, TaBI-1.1 was expressed in mature leaves and roots but not in the hypocotyl or young leaves. Constitutive expression of TaBI-1.1 in Arabidopsis enhanced its resistance to Pseudomonas syringae pv. Tomato (Pst DC3000 infection and induced SA-related gene expression. Additionally, TaBI-1.1 transgenic Arabidopsis exhibited an alleviation of damage caused by high concentrations of SA and decreased the sensitivity to ABA. Consistent with the phenotype, the RNA-seq analysis of 35S::TaBI-1.1 and Col-0 plants showed that TaBI-1.1 was involved in biotic stresses. These results suggested that TaBI-1.1 positively regulates SA signals and plays important roles in the response to biotic stresses. In addition, TaBI-1.1 interacted with the aquaporin TaPIP1, and both them were localized to ER membrane. Furthermore, we demonstrated that TaPIP1 was up-regulated by SA treatment and TaPIP1 transgenic Arabidopsis enhanced the resistance to Pst DC3000 infection. Thus, the interaction between TaBI-1.1 and TaPIP1 on the ER membrane probably occurs in response to SA signals and defense response.

Characterization of regionally associated feline immunodeficiency virus (FIV) in bobcats (Lynx rufus).

Science.gov (United States)

Lagana, Danielle M; Lee, Justin S; Lewis, Jesse S; Bevins, Sarah N; Carver, Scott; Sweanor, Linda L; McBride, Roy; McBride, Caleb; Crooks, Kevin R; VandeWoude, Sue

2013-07-01

Feline immunodeficiency virus (FIV) classically infects felid species with highly divergent species-specific FIVs. However, recent studies have detected an FIV strain infecting both bobcats (Lynx rufus) and pumas (Puma concolor) in California and Florida. To further investigate this observation, we evaluated FIV from bobcats in Florida (n=25) and Colorado (n=80) between 2008 and 2011. Partial viral sequences from five Florida bobcats cluster with previously published sequences from Florida panthers. We did not detect FIV in Colorado bobcats.

No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

Directory of Open Access Journals (Sweden)

Ohlemiller Kevin K

2010-07-01

Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

Flavanols from evening primrose (Oenothera paradoxa) defatted seeds inhibit prostate cells invasiveness and cause changes in Bcl-2/Bax mRNA ratio.

Science.gov (United States)

Lewandowska, Urszula; Szewczyk, Karolina; Owczarek, Katarzyna; Hrabec, Zbigniew; Podsędek, Anna; Koziołkiewicz, Maria; Hrabec, Elżbieta

2013-03-27

In this study, we assessed the influence of an evening primrose flavanol preparation (EPFP) on proliferation and invasiveness of human prostate cancer cells (DU 145) and immortalized prostate epithelial cells (PNT1A). We report for the first time that EPFP reduces DU 145 cell proliferation (IC50 = 97 μM GAE for 72 h incubation) and invasiveness (by 24% versus control at 75 μM GAE). EPFP strongly inhibited PNT1A invasiveness in a concentration-dependent manner (by 67% versus control at 75 μM GAE) and did not cause a reduction in their proliferation. Furthermore, EPFP inhibited the activities of MMP-2 and MMP-9 secreted to culture medium by PNT1A cells by 84% and 34% versus control at 100 μM GAE, respectively. In the case of DU 145, MMP-9 activity at 100 μM GAE was reduced by 37% versus control. Moreover, the evening primrose seed flavanols suppressed the expression of selected genes (MMP-1, MMP-9, MMP-14, c-Fos, c-Jun, and VEGF) and also caused favorable changes in Bcl-2/Bax mRNA ratio which render DU 145 cells more sensitive to apoptosis-triggering agents. An additional confirmation of the proapoptotic activity of EPFP toward DU 145 was visualization of characteristic apoptotic bodies by DAPI staining. In conclusion, this study suggests that EPFP may increase apoptosis and reduce angiogenesis of prostate cancer cells.

Health Promotion Education

DEFF Research Database (Denmark)

Lehn-Christiansen, Sine

The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills are concei......The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills...

p53-Induced Apoptosis Occurs in the Absence of p14ARF in Malignant Pleural Mesothelioma

Directory of Open Access Journals (Sweden)

Sally Hopkins-Donaldson

2006-07-01

Full Text Available Malignant pleural mesotheliomas (MPMs are usually wild type for the p53 gene but contain homozygous deletions in the INK4A locus that encodes p14ARF, an inhibitor of p53-MDM2 interaction. Previous findings suggest that lack of p14ARF expression and the presence of SV40 large T antigen (L-Tag result in p53 inactivation in MPM. We did not detect SV40 L-Tag mRNA in either MPM cell lines or primary cultures, treatment of p14ARF-deficient cells with cisplatin (CDDP increased both total and phosphorylated p53 and enhanced p53 DNA-binding activity. On incubation with CDDP, levels of positively regulated p53 transcriptional targets p21WAF, PIG3, MDM2, Bax, PUMA increased in p14ARF-deficient cells, whereas negatively regulated survivin decreased. Significantly, p53-induced apoptosis was activated by CDDP in p14ARF-deficient cells, treatment with p53-specific siRNA rendered them more CDDP-resistant. p53 was also activated by: 1 inhibition of MDM2 (using nutlin-3; 2 transient overexpression of p14ARF; and 3 targeting of survivin using antisense oligonucleotides. However, it is noteworthy that only survivin downregulation sensitized cells to CDDP-induced apoptosis. These results suggest that p53 is functional in the absence of p14ARF in MPM and that targeting of the downstream apoptosis inhibitor survivin can sensitize to CDDP-induced apoptosis.

Deletion of the N-terminus of IKKγ induces apoptosis in keratinocytes and impairs the AKT/PTEN signaling pathway

International Nuclear Information System (INIS)

Leis, Hugo; Sanchis, Ana; Perez, Paloma

2007-01-01

The regulatory subunit IKKγ/NEMO is crucial for skin development and function and although devoid of kinase activity, loss of IKKγ function completely abolishes the activation of NF-κB by all pro-inflammatory cytokines. To inhibit the IκB kinase (IKK) complex in keratinocytes, we have used a dominant negative approach by generating stable transfectants of an N-terminal deletion of IKKγ (IKKγ-DN97) that uncouples formation of the IKK complex. Expression of this mutant in PB keratinocytes (PB-IKKγ-DN97) delayed growth kinetics, caused morphological changes and dramatically augmented apoptosis even in the absence of pro-apoptotic stimuli, as determined by cell morphology, TUNEL and caspase-3 cleavage. Moreover, in PB-IKKγ-DN97 cells, TNF-α and IL-1 treatment failed to induce degradation of IκBα, phosphorylation of p65 on Ser 536 and nuclear translocation which, consequently, reduced κB-binding activity. In PB-IKKγ-DN97 cells, accumulation of IκBα correlated with a downregulation of AKT activity and an increase of PTEN protein levels whereas pro-apoptotic p53 target genes Bax and Puma were upregulated. These effects were most likely mediated through IKK since coexpression of the wild-type form of IKKγ in keratinocytes partially reversed apoptosis and reduced PTEN expression. Thus, our data suggest a negative cross-talk mechanism involving PTEN and NF-κB, critical for the anti-apoptotic role of NF-κB in keratinocytes

Low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro

International Nuclear Information System (INIS)

Sakurai, Toshiharu; Itoh, Katsuhiko; Liu Yu; Higashitsuji, Hiroaki; Sumitomo, Yasuhiko; Sakamaki, Kazuhiro; Fujita, Jun

2005-01-01

Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we examined the effects of low temperature (32 deg. C) on cells exposed to a variety of stress in vitro. We found that 32 deg. C suppressed induction of apoptosis by cytotoxic stimuli such as adriamycin, etoposide, thapsigargin, NaCl, H 2 O 2 , and anti-Fas antibody. In adriamycin-treated BALB/3T3 cells, the down-shift in temperature from 37 deg. C to 32 deg. C increased the Bcl-xL protein level and decreased the mRNA level of Puma and mitochondrial translocation of Bax, suppressing caspase-9-mediated apoptosis. Furthermore, the protein level and stability of p53 were decreased, and its nuclear export was increased concomitant with Mdm2 mRNA upregulation. The low temperature effect was not observed in p53 -/- /Mdm2 -/- mouse embryonic fibroblasts, suggesting that the effect is mediated by suppression of the p53 pathway. In contrast, while thapsigargin-induced apoptosis was suppressed by the low temperature, no effect on the p53 protein level was observed. Furthermore, the survival rate of p53 -/- /Mdm2 -/- cells exposed to thapsigargin was increased when cultured at 32 deg. C compared with 37 deg. C. In conclusion, mild hypothermia protects cells from a variety of stress by p53-dependent and p53-independent mechanisms

Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.

Science.gov (United States)

Hirsch, Matthew L; Fagan, B Matthew; Dumitru, Raluca; Bower, Jacquelyn J; Yadav, Swati; Porteus, Matthew H; Pevny, Larysa H; Samulski, R Jude

2011-01-01

Human embryonic stem cells (hESCs) are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV) single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.

Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.

Directory of Open Access Journals (Sweden)

Matthew L Hirsch

Full Text Available Human embryonic stem cells (hESCs are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.

Zmpste24-/- mouse model for senescent wound healing research.

Science.gov (United States)

Butala, Parag; Szpalski, Caroline; Soares, Marc; Davidson, Edward H; Knobel, Denis; Warren, Stephen M

2012-12-01

The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing. Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

Glass fiber sensors for detecting special nuclear materials at portal and monitor stations

International Nuclear Information System (INIS)

Hull, C.D.; Seymour, R.; Crawford, T.; Bliss, M.; Craig, R.A.

2001-01-01

Nuclear Safeguards and Security Systems LLC (NucSafe) participated in the Illicit Trafficking Radiation Assessment Program (ITRAP) recently conducted by the Austrian Research Center, Seibersdorf (ARCS) for IAEA, INTERPOL, and the World Customs Organization (IAEA, in press). This presentation reviews ITRAP test results of NucSafe instrumentation. NucSafe produces stationary, mobile, and hand-held systems that use neutron and gamma ray sensors to detect Special Nuclear Materials (SNM). Neutron sensors are comprised of scintillating glass fibers (trade name 'PUMA' for Pu Materials Analysis), which provide several advantages over 3 He and 10 BF 3 tubes. PUMA 6 Li glass fiber sensors offer greater neutron sensitivity and dynamic counting range with significantly less microphonic susceptibility than tubes, while eliminating transport and operational hazards. PUMA sensors also cost less per active area than gas tubes, which is important since rapid neutron detection at passenger, freight, and vehicle portals require large sensor areas to provide the required sensitivity

Perceptions of health promoters about health promotion ...

African Journals Online (AJOL)

2013-02-11

Feb 11, 2013 ... regarding a health promotion programme for families with ... to contribute to high rates of not going to school (ibid. ... sector in order, amongst other objectives, to prevent health ... exercise and mental health promotion must be incorporated ..... (2009:141) identified ignorance and misconception about the.

Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

International Nuclear Information System (INIS)

Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun; Shin, Ki Soon; Kang, Shin Jung

2013-01-01

Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD

Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

Energy Technology Data Exchange (ETDEWEB)

Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of); Shin, Ki Soon [Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kang, Shin Jung, E-mail: sjkang@sejong.ac.kr [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of)

2013-08-09

Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.

Health Promotion

DEFF Research Database (Denmark)

Povlsen, Lene; Borup, I.

2015-01-01

and Adolescent Health Promotion', Salutogenesis - from theory to practice' and Health, Stress and Coping'. More than half of all doctoral theses undertaken at NHV during these years had health promotion as their theme. As a derivative, the Nordic Health Promotion Research Network (NHPRN) was established in 2007......In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...

Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic cell lines.

Science.gov (United States)

Serafin, Antonio M; Bohm, Lothar

2005-01-01

The administration of cancer chemotherapeutic agents results in an increase in the apoptotic cells in the tumor: therefore, it has been assumed that anticancer drugs exhibit their cytotoxic effects via apoptotic signaling pathways. Characteristics that confer sensitivity to drug-induced apoptosis are, a functional p53 protein and expression of the apoptosis-promoting protein, bax. The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD(50) concentrations of etoposide, vinblastine and estramustine. Cell death was monitored morphologically by fluorescent microscopy, and by flow cytometry (Annexin-V assay). Apoptotic morphology was rather low and ranged from 0.1% to 12.1%, 3.0% to 6.0% and 0.1% to 8.5% for etoposide, estramustine and vinblastine, respectively. Annexin-V binding and flow cytometry indicated apoptotic propensities of 0% to 4%, 0% to 3% and 0% to 5%, respectively. The percentage of cells responding to drug-induced apoptosis was, on average, higher in the tumor cell lines than in the normal cell lines, but showed no correlation with p53 status. The percentage of cells showing necrosis, assessed by Annexin binding and Propidium Iodide permeability in aqueous medium, tended to be much higher, and was found to be at the level of 5% to 30%. Immunoblotting demonstrated that bax and bcl-2 proteins were expressed at a basal level in all cell lines, but did not increase after exposure to TD(50) doses of the three drugs. The ratio of bax and bcl-2, measured by laser scanning densitometry, was not altered by the drug-induced DNA damage. The results suggest that apoptosis is not a major mechanism of drug-induced cell death in prostate cell lines and appears to be independent of p53 status and bax/bcl-2 expression.

3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

Science.gov (United States)

Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

2016-06-17

Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

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Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

2016-04-01

The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis.

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Rie Ibusuki

Full Text Available Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1.Transgenic (TG mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro.After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro.HNP-1 secreted by neutrophils may exacerbate alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2 expression and an increase in miR-34a-5p expression.

Decreased expression of MUC1 induces apoptosis and inhibits migration in pancreatic cancer PANC-1 cells via regulation of Slug pathway.

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Zhao, Ping; Meng, Meng; Xu, Bin; Dong, Aiping; Ni, Guangzhen; Lu, Lianfang

2017-12-06

MUC1, a membrane tethered mucin glycoprotein, is overexpressed in > 60% of human pancreatic cancers (PCs), and is associated with poor prognosis and enhanced metastasis. Here, we report the effect of silencing MUC1 expression on the growth, migration and invasive ability of pancreatic cancer cells, and explored its mechanisms. We observed that siRNA mediated suppression of the MUC1 expression significantly reduced invasive and migrative capability and induced apoptosis of the pancreatic cancer PANC-1 cells. We found that Slug was inhibited in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Expression of PUMA and E-cadherin was increased in the MUC1 siRNA/PANC-1 cells. PANC-1 cells overexpressing full long Slug gene (when transfected with Slug cDNA plasmid) significantly inhibited PUMA and E-cadherin expression in the MUC1 siRNA/PANC-1 cells. Silencing PUMA expression inhibited apoptosis in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Silencing E-cadherin expression restored the invasion and migration ability in the MUC1 siRNA/PANC-1 cells. We therefore concluded that silencing MUC1 expression inhibited migration and invasion, and induced apoptosis of PANC-1 cells via downregulation of Slug and upregulation of Slug dependent PUMA and E-cadherin expression. MUC1 could serve as a potential therapeutic target in pancreatic cancer.

Seroprevalence and genomic divergence of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species.

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Troyer, Jennifer L; Pecon-Slattery, Jill; Roelke, Melody E; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A; Revilla, Eloy; O'Brien, Stephen J

2005-07-01

Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today.

Seroprevalence and Genomic Divergence of Circulating Strains of Feline Immunodeficiency Virus among Felidae and Hyaenidae Species†

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Troyer, Jennifer L.; Pecon-Slattery, Jill; Roelke, Melody E.; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A.; Revilla, Eloy; O'Brien, Stephen J.

2005-01-01

Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today. PMID:15956574

Methylprednisolone promotes recovery of neurological function after spinal cord injury: association with Wnt/β-catenin signaling pathway activation

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Lu, Gong-biao; Niu, Fu-wen; Zhang, Ying-chun; Du, Lin; Liang, Zhi-yuan; Gao, Yuan; Yan, Ting-zhen; Nie, Zhi-kui; Gao, Kai

2016-01-01

Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specific proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are significantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery after spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment significantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. The number of surviving motor neurons increased, whereas the lesion size significantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. These results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway. PMID:28123427

Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression

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Kumari Ratna

2010-07-01

Full Text Available Abstract Background p53 is the most studied tumor suppressor and its overexpression may or may not cause cell death depending upon the genetic background of the cells. p53 is degraded by human papillomavirus (HPV E6 protein in cervical carcinoma. Several stress activated kinases are known to phosphorylate p53 and, among them cyclin dependent kinase 5 (Cdk5 is one of the kinase studied in neuronal cell system. Recently, the involvement of Cdk5 in phosphorylating p53 has been shown in certain cancer types. Phosphorylation at specific serine residues in p53 is essential for it to cause cell growth inhibition. Activation of p53 under non stress conditions is poorly understood. Therefore, the activation of p53 and detection of upstream kinases that phosphorylate non-genotoxically overexpressed p53 will be of therapeutic importance for cancer treatment. Results To determine the non-genotoxic effect of p53; Tet-On system was utilized and p53 inducible HPV-positive HeLa cells were developed. p53 overexpression in HPV-positive cells did not induce cell cycle arrest or apoptosis. However, we demonstrate that overexpressed p53 can be activated to upregulate p21 and Bax which causes G2 arrest and apoptosis, by inhibiting protein phosphatase 2A. Additionally, we report that the upstream kinase cyclin dependent kinase 5 interacts with p53 to phosphorylate it at Serine20 and Serine46 residues thereby promoting its recruitment on p21 and bax promoters. Upregulation and translocation of Bax causes apoptosis through intrinsic mitochondrial pathway. Interestingly, overexpressed activated p53 specifically inhibits cell-growth and causes regression in vivo tumor growth as well. Conclusion Present study details the mechanism of activation of p53 and puts forth the possibility of p53 gene therapy to work in HPV positive cervical carcinoma.

Allergen-Removed Rhus verniciflua Extract Induces Ovarian Cancer Cell Death via JNK Activation.

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Kang, Se-Hui; Hwang, In-Hu; Son, Eunju; Cho, Chong-Kwan; Choi, Jong-Soon; Park, Soo-Jung; Jang, Byeong-Churl; Lee, Kyung-Bok; Lee, Zee-Won; Lee, Jong Hoon; Yoo, Hwa-Seung; Jang, Ik-Soon

2016-01-01

Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.

SPORT PROMOTION STRATEGIES

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Alexandru Lucian MIHAI

2013-10-01

Full Text Available In sport marketing, the word promotion covers a range of interrelated activities. All of these activities are designed to attract attention, stimulate the interest and awareness of consumers, and of course, encourage them to purchase a sport product. Promotion is about communicating with and educating consumers. The purpose of a sport promotional strategy is to build brand loyalty and product credibility, develop image, and position the brand. A promotional strategy is similar to a marketing strategy, but the promotional strategy seeks short-term objectives, both direct and indirect. Promotional objectives usually include increased sales, stimulate impulse buying, raise customer traffic, and present and reinforce image. It also provides information about products and services, publicizes new stores or websites, and creates and enhances customer satisfaction.

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway

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Fan Zhang

2018-05-01

Full Text Available Objective: Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Methods: Female adult Wistar rats were randomly divided into three groups (n = 15 per group: control (CON group, SCH group and overt hypothyroidism (OH group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP and Morris water-maze (MWM test. The protein expression of the p75 neurotrophin receptor (p75NTR, phospho-c-Jun N-terminal kinase (p-JNK, the pro-apoptotic protein p53 and Bax were detected by Western blotting. Results: The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75NTR, p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Conclusions: Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex.

Endoplasmic reticulum stress and IRE-1 signaling cause apoptosis in colon cancer cells in response to andrographolide treatment.

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Banerjee, Aditi; Ahmed, Hafiz; Yang, Peixin; Czinn, Steven J; Blanchard, Thomas G

2016-07-05

The plant metabolite andrographolide induces cell cycle arrest and apoptosis in cancer cells. The mechanism(s) by which andrographolide induces apoptosis however, have not been elucidated. The present study was performed to determine the molecular events that promote apoptosis in andrographolide treated cells using T84, HCT116 and COLO 205 colon cancer cell lines. Andrographolide was determined to limit colony formation and Ki67 expression, alter nuclear morphology, increase cytoplasmic histone-associated-DNA-fragments, and increase cleaved caspase-3 levels. Andrographolide also induced significantly higher expression of endoplasmic reticulum (ER) stress proteins GRP-78 and IRE-1 by 48 h but not PERK or ATF6. Apoptosis signaling molecules BAX, spliced XBP-1 and CHOP were also significantly increased. Moreover, chemical inhibition of ER stress or IRE-1 depletion with siRNA in andrographolide treated cells significantly limited expression of IRE-1 and CHOP as determined by immunofluorescence staining, real time PCR, or immunobloting. This was accompanied by a decreased BAX/Bcl-2 ratio. Andrographolide significantly promotes cancer cell death compared to normal cells. These data demonstrate that andrographolide associated ER stress contributes to apoptosis through the activation of a pro-apoptotic GRP-78/IRE-1/XBP-1/CHOP signaling pathway.

The study on Egr-1 promoter which is radioactive promoter

International Nuclear Information System (INIS)

Zhang Chunzhi; Guo Yang; Lv Zhonghong

2006-01-01

Radiogenetic therapy is a heated reaseach on oncotherapy. Early growth response gene-1 (Egr-1) gene promoter is a probably means in radiogenetic therapy. The article review studying on Egr-1 gene promoter and constructing regulating gene expressing system by radiation-inducible Egr-1 gene promoter. (authors)

Bax/Tubulin/Epithelial-Mesenchymal Pathways Determine the Efficacy of Silybin Analog HM015k in Colorectal Cancer Cell Growth and Metastasis

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Haneen Amawi

2018-05-01

Full Text Available The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT, are involved in the progression, metastasis, and resistance of colorectal cancer (CRC to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a−15k and compound 17, were screened for cytotoxicity in CRC cell lines. Compounds HM015j and HM015k (15k and 15j significantly decreased cell proliferation, inhibited colony formation, and produced cell cycle arrest in CRC cells. Furthermore, 15k significantly induced the formation of reactive oxygen species and apoptosis. It induced the cleavage of the intrinsic apoptotic protein (Bax p21 to its more efficacious fragment, p18. Compound 15k also inhibited tubulin expression and disrupted its structure. Compound 15k significantly decreased metastatic LOVO cell migration and invasion. Furthermore, 15k reversed mesenchymal morphology in HCT116 and LOVO cells. Additionally, 15k significantly inhibited the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker, E-cadherin. Compound 15k inhibited the expression of key proteins known to induce EMT (i.e., DVL3, β-catenin, c-Myc and upregulated the anti-metastatic protein, cyclin B1. Overall, in vitro, 15k significantly inhibited CRC progression and metastasis by inhibiting apoptosis, tubulin activity and the EMT pathways. Overall, these data suggest that compound 15k should be tested in vivo in a CRC animal model for further development.

Radiation promotive concept

International Nuclear Information System (INIS)

Shebaita, M.K.

1975-01-01

The concept of radiation promotion was proposed in this study. The proposal of this concept was dependent upon stimulation in growth weight of survived chicks when fertile eggs were exposed to 60 Co gamma radiation. It was found that female chick (Promotive Sex) responded to this proposal concept rather than the male. Moreover, the dose level of 640 rads was found to be the Promotive Dose. It is important before applying ionizing radiation as a growth promotive to take into consideration whether you want increasing egg or meat production, as meat promotion in layers breed is bound to decrease egg production. (orig.) [de

Promoting Health in Early Childhood Environments: A Health-Promotion Approach

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Minniss, Fiona Rowe; Wardrope, Cheryl; Johnston, Donni; Kendall, Elizabeth

2013-01-01

This paper investigates the mechanisms by which a health-promotion intervention might influence the health-promoting behaviours of staff members working in early childhood centres. The intervention was an ecological health-promotion initiative that was implemented within four early childhood centres in South-East Queensland, Australia. In-depth,…

[Population estimates and conservation of felids (Carnivora: Felidae) in Northern Quintana Roo, Mexico].

Science.gov (United States)

Ávila-Nájera, Dulce María; Chávez, Cuauhtémoc; Lazcano-Barrero, Marco A; Pérez-Elizalde, Sergio; Alcántara-Carbajal, José Luis

2015-09-01

Wildlife density estimates provide an idea of the current state of populations, and in some cases, reflect the conservation status of ecosystems, essential aspects for effective management actions. In Mexico, several regions have been identified as high priority areas for the conservation of species that have some level of risk, like the Yucatan Peninsula (YP), where the country has the largest population of jaguars. However, little is known about the current status of threatened and endangered felids, which coexist in the Northeastern portion of the Peninsula. Our objective was to estimate the wild cats' density population over time at El Eden Ecological Reserve (EEER) and its surrounding areas. Camera trap surveys over four years (2008, 2010, 2011 and 2012) were conducted, and data were obtained with the use of capture-recapture models for closed populations (CAPTURE + MMDM or 1/2 MMDM), and the spatially explicit capture-recapture model (SPACECAP). The species studied were jaguar (Panthera onca), puma (Puma concolor), ocelot (Leopardus pardalis), jaguarundi (Puma yaguaroundi) and margay (Leopardus wiedii). Capture frequency was obtained for all five species and the density for three (individuals/100km2). The density estimated with The Mean Maximum Distance Moved (MMDM), CAPTURE, ranged from 1.2 to 2.6 for jaguars, from 1.7 to 4.3 for pumas and from 1.4 to 13.8 for ocelots. The density estimates in SPACECAP ranged from 0.7 to 3.6 for jaguars, from 1.8 to 5.2 for pumas and 2.1 to 5.1 for ocelots. Spatially explicit capture recapture (SECR) methods in SPACECAP were less likely to overestimate densities, making it a useful tool in the planning and decision making process for the conservation of these species. The Northeastern portion of the Yucatan Peninsula maintains high populations of cats, the EEER and its surrounding areas are valuable sites for the conservation of this group of predators. Rev. Biol.

Del-1 overexpression potentiates lung cancer cell proliferation and invasion

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Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2015-12-04

Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells. �

Del-1 overexpression potentiates lung cancer cell proliferation and invasion

International Nuclear Information System (INIS)

Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

2015-01-01

Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells. �

Promoting preschool reading

OpenAIRE

Istenič, Vesna

2013-01-01

The thesis titled Promoting preschool reading consists of a theoretiral and an empirical part. In the theoretical part I wrote about reading, the importance of reading, types of reading, about reading motivation, promoting reading motivation, internal and external motivation, influence of reading motivation on the child's reading activity, reading and familial literacy, the role of adults in promotion reading literacy, reading to a child and promoting reading in pre-school years, where I ...

p53 inactivation decreases dependence on estrogen/ERK signalling for proliferation but promotes EMT and susceptility to 3-bromopyruvate in ERα+ breast cancer MCF-7 cells.

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Rieber, Manuel; Strasberg-Rieber, Mary

2014-03-15

Most breast cancers express the estrogen receptor alpha (ERα(+)), harbor wt TP53, depend on estrogen/ERK signalling for proliferation, and respond to anti-estrogens. However, concomittant activation of the epidermal growth factor receptor (EGFR)/MEK pathway promotes resistance by decreasing estrogen dependence. Previously, we showed that retroviral transduction of mutant p53 R175H into wt TP53 ERα(+) MCF-7 cells induces epidermal growth factor (EGF)-independent proliferation, activation of the EGF receptor (p-EGFR) and some characteristics of epithelial-mesenchymal transition (EMT). To investigate whether p53 inactivation augments ERα(+) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. Introduction of mutant p53 R175H lowered expression of p53-dependent PUMA and p21WAF1, decreased E-cadherin and cytokeratin 18 associated with EMT, but increased the % of proliferating ERα(+)/Ki67 cells, diminishing estrogen dependence. These cells also exhibited higher proliferation in the presence of MEK-inhibitor UO126, reciprocally correlating with preferential susceptibility to the pyruvate analog 3-bromopyruvate (3-BrPA) without a comparable response to 2-deoxyglucose. p53 siRNA silencing by electroporation in wt TP53 MCF-7 cells also decreased estrogen dependence and response to MEK inhibition, while also conferring susceptibility to 3-BrPA. (a) ERα(+) breast cancer cells dysfunctional for TP53 which proliferate irrespective of low estrogen and chemical MEK inhibition are likely to increase metabolic consumption becoming increasingly susceptible to 3-BrPA; (b) targeting the pyruvate pathway may improve response to endocrine therapy in ERα(+) breast cancer with p53 dysfunction. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

7α-Hydroxy-β-Sitosterol from Chisocheton tomentosus Induces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation

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Mohammad Tasyriq

2012-01-01

Full Text Available In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1, a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.

The role of landowners in jaguar conservation in Sonora, Mexico.

Science.gov (United States)

Rosas-Rosas, Octavio C; Valdez, Raul

2010-04-01

The northernmost known breeding population of jaguars occurs in the municipality of Nácori Chico, Sonora, Mexico about 270 km from the United States-Mexico border and may be the source from which jaguars sighted in the United States dispersed. Since 1999 at least 11 jaguars (Panthera onca) had been illegally killed in the area due to predator control programs. We initiated a jaguar landowner-based conservation plan in 2004. The eight participating landowners agreed to suspend predator control programs targeting jaguars and pumas (Puma concolor) only if cattle losses were compensated. A private outfitter, with the consent of landowners, initiated white-tailed deer (Odocoileus virginianus) hunts in 2004 and agreed to pay the group of participating landowners US$1500 for every deer hunt permit sold. The funds paid to the landowners from deer hunts were sufficient to convince landowners to suspend all predator-control efforts of jaguars and pumas. The involvement of landowners in the jaguar conservation program in northeastern Sonora is a successful, private, wildlife-conservation initiative that provides an example for jaguar conservation efforts in northern Mexico.

Preliminary Flight Software Specification for the Petite Amateur Navy Satellite (PANSAT)

Science.gov (United States)

1994-03-01

8217p bax: array(4J of AbstractBax-Chmnnel( Bax,.End) kudlvihdua queue; end; module DATA TRANSFER TYPE syunrCeWs; (Between BAX and FTA ’p pc: arroy...proided ( CURRENT COMMAND(command) = dir short cmd or CURRENTSOMAD command) =dfir long.. Fmd ) aMW so ( (command.info(O..31 < > OxOOOOOOO and

Streamlining Appointment, Promotion, and Tenure Procedures to Promote Early-Career Faculty Success.

Science.gov (United States)

Smith, Shannon B; Hollerbach, Ann; Donato, Annemarie Sipkes; Edlund, Barbara J; Atz, Teresa; Kelechi, Teresa J

2016-01-01

A critical component of the progression of a successful academic career is being promoted in rank. Early-career faculty are required to have an understanding of appointment, promotion, and tenure (APT) guidelines, but many factors often impede this understanding, thwarting a smooth and planned promotion pathway for professional advancement. This article outlines the steps taken by an APT committee to improve the promotion process from instructor to assistant professor. Six sigma's DMAIC improvement model was selected as the guiding operational framework to remove variation in the promotion process. After faculty handbook revisions were made, several checklists developed, and a process review rubric was implemented; recently promoted faculty were surveyed on satisfaction with the process. Faculty opinions captured in the survey suggest increased transparency in the process and perceived support offered by the APT committee. Positive outcomes include a strengthened faculty support framework, streamlined promotion processes, and improved faculty satisfaction. Changes to the APT processes resulted in an unambiguous and standardized pathway for successful promotion. Copyright © 2016 Elsevier Inc. All rights reserved.

Promoter2.0: for the recognition of PolII promoter sequences

DEFF Research Database (Denmark)

Knudsen, Steen; Knudsen, Steen

1999-01-01

transcription start sites. On standardized test setsconsisting of human genomic DNA, the performance of Promoter2.0 compares well with other softwaredeveloped for the same purpose. Availability : Promoter2.0 is available as a Web server at http://www.cbs.dtu.dk/services/promoter/ Contact : steen@cbs.dtu.dk...

Health-promoting schools

DEFF Research Database (Denmark)

Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M

2005-01-01

Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling...... them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...

What Is a Promotion?

Science.gov (United States)

Pergamit, Michael R.; Veum, Jonathan R.

1999-01-01

For a sample of young workers, "promotion" involved no change in position or duties; promotion was more likely for males than females and Whites than Blacks or Hispanics. Company training and prior promotions were important predictors. Promotion did not appear to have a direct impact on job satisfaction. (SK)

Promoter2.0: for the recognition of PolII promoter sequences

DEFF Research Database (Denmark)

Knudsen, Steen; Knudsen, Steen

1999-01-01

Motivation : A new approach to the prediction of eukaryotic PolII promoters from DNA sequence takesadvantage of a combination of elements similar to neural networks and genetic algorithms to recognize a set ofdiscrete subpatterns with variable separation as one pattern: a promoter. The neural...... of optimization, the algorithm was able todiscriminate between vertebrate promoter and non-promoter sequences in a test set with a correlationcoefficient of 0.63. In addition, all five known transcription start sites on the plus strand of the completeadenovirus genome were within 161 bp of 35 predicted...

Promoting mental health as an essential aspect of health promotion.

Science.gov (United States)

Sturgeon, Shona

2006-12-01

This paper advocates that mental health promotion receive appropriate attention within health promotion. It is of great concern that, in practice, mental health promotion is frequently overlooked in health promotion programmes although the WHO definitions of health and the Ottawa Charter describe mental health as an integral part of health. It is suggested that more attention be given to addressing the determinants of mental health in terms of protective and risk factors for both physical and mental conditions, particularly in developing countries. Examples of evidence-based mental health programmes operating in widely diverse settings are presented to demonstrate that well designed interventions can contribute to the well-being of populations. It is advocated that particular attention be given to the intersectorial cooperation needed for this work.

Data describing the effect of DRD4 promoter polymorphisms on promoter activity

Directory of Open Access Journals (Sweden)

Shoin Tei

2016-06-01

Full Text Available This data article tested whether polymorphisms within the dopamine D4 receptor (DRD4 gene promoter can lead to differences in the promoter activity. The variants, a 120-bp variable number tandem repeat (VNTR, −906 T/C, −809 G/A, −616G/C, and −521C/T, were introduced into the DRD4 promoter and the promoter activity was measured in a neural cell line using the luciferase assay. However, no differences were detected among the haplotypes investigated, and the in vitro data obtained from our protocol could not support the involvement of DRD4 promoter polymorphisms in heritable human traits.

Promotion primer. Foerderfibel

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

This revised edition of the promotion primer is to serve as a topical orientation aid for industrial firms, unions, boards and other bodies interested where the actions of governmental R and D and innovation policy are compiled and clearly arranged. It is important for the success of governmental aids that the institutions concerned are informed about all possibilities of the promotion, financing and advisory programme. Beyond the presentation of the research promotion sectors, the fiscal measures and the contractual as well as the joint research this revised edition focussess on the fields of consultative services for innovation and information. For many firms the access to qualified information and guidance is of particular importance. That is why this brochure points out the ways towards governmental research promotion. The BMFT has provided a remarkable contribution to research promotion by establishing information and consultative services for trade and industry.

Activity of Metabotropic Glutamate Receptor 4 Suppresses Proliferation and Promotes Apoptosis With Inhibition of Gli-1 in Human Glioblastoma Cells

Directory of Open Access Journals (Sweden)

Zhichao Zhang

2018-05-01

Full Text Available Glioblastoma multiforme (GBM is the most lethal glioma variant in the adult brain and among the deadliest of human cancers. Increasing evidence has shown that metabotropic glutamate receptor subtype 4 (mGluR4 expression may play roles in regulating the growth of neural stem cells as well as several cancer cell lines. Here, we investigated the effects of mGluR4 on the growth and apoptosis of the LN229 GBM cell line. Involvement of Gli-1, one of the key transcription factors in the sonic Hedgehog (SHH signaling pathway, was further explored. In this study, mGluR4 was activated using selective agonist VU0155041; and gene-targeted siRNAs were used to generate loss of function of mGluR4 and Gli-1 in LN229 cells. The results demonstrated that LN229 cells expressed mGluR4 and the agonist VU0155041 decreased cell viability in a dose- and time-dependent manner. Activation of mGluR4 inhibited cyclin D1 expression, activated pro-caspase-8/9/3, and disrupted the balance of Bcl-2/Bax expression, which indicated cell cycle arrest and apoptosis of LN229 cells, respectively. Furthermore, Gli-1 expression was reduced by mGluR4 activation in LN229 cells, and downregulation of Gli-1 expression by gene-targeted siRNA resulted in both inhibition of cell proliferation and promotion of apoptosis. Moreover, VU0155041 treatment substantially blocked SHH-induced cyclin D1 expression and cell proliferation, while increasing TUNEL-positive cells and the activation of apoptosis-related proteins. We concluded that activation of mGluR4 expressed in LN229 cells could inhibit GBM cell growth by decreasing cell proliferation and promoting apoptosis. Further suppression of intracellular Gli-1 expression might be involved in the action of mGluR4 on cancer cells. Our study suggested a novel role of mGluR4, which might serve as a potential drug target for control of GBM cell growth.

1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl Ethanone-Induced Cell Cycle Arrest in G1/G0 in HT-29 Cells Human Colon Adenocarcinoma Cells

Directory of Open Access Journals (Sweden)

Ma Ma Lay

2014-01-01

Full Text Available 1-(2,6-Dihydroxy-4-methoxyphenyl-2-(4-hydroxyphenyl ethanone (DMHE was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff. Boerl fruits and the structure confirmed by GC-MS (gas chromatography-mass spectrometry and NMR (nuclear magnetic resonance analysis. This compound was tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of transcriptional and translational cell proliferation assay. The results of MTT assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose- and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72 h incubation. Morphological features of apoptotic cells upon treatment by DMHE, e.g., cell shrinkage and membrane blebbing, were examined by an inverted and phase microscope. Other features, such as chromatin condension and nuclear fragmentation were studied using acridine orange and propidium iodide staining under the fluorescence microscope. Future evidence of apoptosis/necrosis was provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium iodide staining revealed the percentage of early apoptotic, late apoptotic, necrotic and live cells in a dose- and time-dependent manner using flow cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A western blot analysis indicated that cell death might be associated with the up-regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent manner. The expression of the pro-apoptotic protein Bak was not observed.

7 CFR 1210.312 - Promotion.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1210.312 Section 1210.312 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any...

7 CFR 1216.23 - Promotion.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1216.23 Section 1216.23 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion...

7 CFR 1250.310 - Promotion.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1250.310 Section 1250.310 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.310 Promotion. Promotion means any action, including paid...

7 CFR 1260.122 - Promotion.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1260.122 Section 1260.122 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions § 1260.122 Promotion. Promotion means any action, including paid...

7 CFR 1150.114 - Promotion.

Science.gov (United States)

2010-01-01

... and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.114 Promotion. Promotion means actions such as paid advertising, sales... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1150.114 Section 1150.114 Agriculture...

Deletion analysis of susy-sl promoter for the identification of optimal promoter sequence

International Nuclear Information System (INIS)

Bacha, S.; Khatoon, A.; Asif, M.; Bshir, A.

2015-01-01

The promoter region of sucrose synthase (susy-Sl) was identified and isolated from tomato. The 5? deletion analysis was carried out for the identification of minimum optimal promoter. Transgenic lines of Arabidopsis thaliana were developed by floral dip method incorporating various promoter deletion cassettes controlling GUS reporter gene. GUS assay of transgenic tissues indicated that full length susy-Sl promoter and its deletion mutants were constitutively expressed in vegetative and floral tissues of A. thaliana. The expression was observed in roots, shoots and flowers of A. thaliana. Analysis of 5? deletion series of susy-Sl promoter showed that a minimum of 679 bp fragment of the promoter was sufficient to drive expression of GUS reporter gene in the major tissues of transgenic A. thaliana. (author)

Phase coexistence and magnetic behavior in the low-dimensional hexagonal cobaltites BaxA1-xCoO3-δ (A = Mg or Ca and 0 ⩽ x ⩽ 0.20)

Science.gov (United States)

Oliveira, M. P.; Mercena, S. G.; Meneses, C. T.; Jesus, C. B. R.; Pagliuso, P. G.; Duque, J. G. S.

2018-04-01

In this work, we report on X-ray diffraction and magnetization measurements carried out in the low-dimensional hexagonal cobaltites BaxA1-xCoO3-δ (A = Mg or Ca, 0 ⩽ x ⩽ 0.20 and δ = 0 or 0.4). Polycrystalline samples have been synthesized by solid-state reaction. The Rietveld refinements of the X-ray diffraction patterns show clearly a phase coexistence of both BaCoO2.6 and BaCoO3 hexagonal polytype structures (space group: P63/mmc), which is dependent on both the dopant ion and doping level. At low temperatures (T 0.10 the low temperature hysteresis is not observed anymore. The field-dependence of ZFC-FC curves taken for the sample grown with x = 0 show a displacement of the peak position into low temperature region. Except for the sample grown with x = 0.20, the MvsH loops taken at T = 2 K show multiple steps in the field region ranging - 15 ⩽ H ⩽ 15 kOe . Finally, the saturation magnetization values are consistent with a low-spin state for the Co2+ or Co4+ ions.

Promoters of Escherichia coli versus promoter islands: function and structure comparison.

Directory of Open Access Journals (Sweden)

Valeriy V Panyukov

Full Text Available Expression of bacterial genes takes place under the control of RNA polymerase with exchangeable σ-subunits and multiple transcription factors. A typical promoter region contains one or several overlapping promoters. In the latter case promoters have the same or different σ-specificity and are often subjected to different regulatory stimuli. Genes, transcribed from multiple promoters, have on average higher expression levels. However, recently in the genome of Escherichia coli we found 78 regions with an extremely large number of potential transcription start points (promoter islands, PIs. It was shown that all PIs interact with RNA polymerase in vivo and are able to form transcriptionally competent open complexes both in vitro and in vivo but their transcriptional activity measured by oligonucleotide microarrays was very low, if any. Here we confirmed transcriptional defectiveness of PIs by analyzing the 5'-end specific RNA-seq data, but showed their ability to produce short oligos (9-14 bases. This combination of functional properties indicated a deliberate suppression of transcriptional activity within PIs. According to our data this suppression may be due to a specific conformation of the DNA double helix, which provides an ideal platform for interaction with both RNA polymerase and the histone-like nucleoid protein H-NS. The genomic DNA of E.coli contains therefore several dozen sites optimized by evolution for staying in a heterochromatin-like state. Since almost all promoter islands are associated with horizontally acquired genes, we offer them as specific components of bacterial evolution involved in acquisition of foreign genetic material by turning off the expression of toxic or useless aliens or by providing optimal promoter for beneficial genes. The putative molecular mechanism underlying the appearance of promoter islands within recipient genomes is discussed.

Health promotion in globalization

Directory of Open Access Journals (Sweden)

Álvaro Franco-Giraldo

2012-10-01

Full Text Available Objective: to unravel some theoretical and factual elements required to implement more effective health promotion strategies and practices in the field of health services whilst following the great challenges that globalization has imposed on the health systems, which are inevitably expressed in the local context (glocalization. Methodology: a narrative review taking into account the concepts of globalization and health promotion in relation to health determinants. The authors approach some courses of action and strategies for health promotion based on the social principles and universal values that guide health promotion, health service reorientation and primary healthcare, empowerment, social participation, and inter-sectoral and social mobilization. Discussion: the discussion focuses on the redirection of health promotion services in relation to the wave of health reforms that has spread throughout the world under the neoliberal rule. The author also discusses health promotion, its ineffectiveness, and the quest for renewal. Likewise, the author sets priorities for health promotion in relation to social determinants. Conclusion: the current global order, in terms of international relations, is not consistent with the ethical principles of health promotion. In this paper, the author advocates for the implementation of actions to change the social and physical life conditions of people based on changes in the use of power in society and the appropriate practice of politics in the context of globalization in order to achieve the effectiveness of the actions of health promotion.

FORRAJE Y GRANO DE HÍBRIDOS DE MAÍZ AMARILLOS PARA VALLES ALTOS DE MÉXICO

Directory of Open Access Journals (Sweden)

Margarita Tadeo-Robledo

2012-01-01

Full Text Available El objetivo de este trabajo fue determinar la producción de grano y de forraje en híbridos trilineales amarillos. Se establecieron en el año 2009 tres experimentos, comparando híbridos trilineales amarillos con híbridos comerciales blancos y el híbrido Búho de Asgrow; dos experimentos en el Campo Experimental de Valle de México del INIFAP, donde se evaluó la productividad de grano y otro en la Facultad de Estudios Superiores Cuautitlán de la Universidad Nacional Autónoma de México, para evaluación de forraje a una densidad de 70 000 plantas/ha. El análisis combinado para rendimiento detectó diferencias altamente significativas para híbridos, sitios y la interacción híbridos x sitios. El coeficiente de variación fue de 17,7% y la media general de 7113 kg/ha. La comparación de medias ubicó en el primer grupo de significancia a los híbridos de grano blanco comerciales Puma 1167 y Puma 1163 con 9549 kg/ha y 8748 kg/ha, respectivamente. Los híbridos amarillos 501X497 y 501X555 fueron superiores 36,0% y 12,4% con respecto a H-48 y el híbrido testigo. Búho presentó similar rendimiento en materia verde, que Puma 1163 y fue superior (P<0,05 a los otros híbridos evaluados. El híbrido Puma 1163 por su buen rendimiento de grano, materia verde y materia seca se sugiere validarlo a nivel comercial en doble propósito.

Nerve growth factor reduces apoptotic cell death in rat facial motor neurons after facial nerve injury.

Science.gov (United States)

Hui, Lian; Yuan, Jing; Ren, Zhong; Jiang, Xuejun

2015-01-01

To assess the effects of nerve growth factor (NGF) on motor neurons after induction of a facial nerve lesion, and to compare the effects of different routes of NGF injection on motor neuron survival. This study was carried out in the Department of Otolaryngology Head & Neck Surgery, China Medical University, Liaoning, China from October 2012 to March 2013. Male Wistar rats (n = 65) were randomly assigned into 4 groups: A) healthy controls; B) facial nerve lesion model + normal saline injection; C) facial nerve lesion model + NGF injection through the stylomastoid foramen; D) facial nerve lesion model + intraperitoneal injection of NGF. Apoptotic cell death was detected using the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. Expression of caspase-3 and p53 up-regulated modulator of apoptosis (PUMA) was determined by immunohistochemistry. Injection of NGF significantly reduced cell apoptosis, and also greatly decreased caspase-3 and PUMA expression in injured motor neurons. Group C exhibited better efficacy for preventing cellular apoptosis and decreasing caspase-3 and PUMA expression compared with group D (pfacial nerve injury in rats. The NGF injected through the stylomastoid foramen demonstrated better protective efficacy than when injected intraperitoneally.

Kaolin clays from Patagonia - Argentina. Relationship between the mineralogy and ceramic properties; Arcillas caolinicas de la Patagonia argentina. Relacion entre la mineralogia y las propiedades ceramicas

Energy Technology Data Exchange (ETDEWEB)

Factorovich, J.C.; Badino, D. [Piedra Grande S.A., Buenos Aires (Argentina); Cravero, F.; Dominguez, E. [Universidad Nacional del Sur, Bahia Blanca (Argentina). Dept. de Geologia

1997-12-31

The mineralogy, grain size distribution, chemical composition, S and C contents, plasticity, and cationic exchange capacity are determined in the sedimentary kaolinitic clays from the clay pits Puma Negra, Puma Gris, Tincar Super; and Chenque and Cardenal located in Santa Cruz and Chubut Provinces. Mineralogy and Particle size distribution of > 5, 5-2 and <2{mu} fractions are determined. Modulus of rupture, 1100 and 1250 deg C shrinkage and water absorption and whiteness are found. It is accomplished a statistics correlation between the characteristics of grain size distribution, mineralogy, and other physical properties with the main ceramic properties to understand its influence in the ceramic process. (author) 5 refs., 2 tabs.

Data of expression status of miR- 29a and its putative target mitochondrial apoptosis regulatory gene DRP1 upon miR-15a and miR-214 inhibition

Directory of Open Access Journals (Sweden)

Muhammad Ishtiaq Jan

2018-02-01

Full Text Available Data is about the mitochondrial apoptosis regulatory framework genes PUMA, DRP1 (apoptotic, and ARC (anti-apoptotic analysis after the employment of their controlling miRNAs inhibitors. The data represents putative conserved targeting of seed regions of miR-15a, miR-29a, and miR-214 with respective target genes PUMA, DRP1, and ARC. Data is of cross interference in expression levels of one miRNA family, miR-29a and its putative target DRP1 upon the inhibitory treatment of other miRNAs 15a and 214. Keywords: DRP1, miR-15a, Apoptosis, miRNAs inhibition

Kaolin clays from Patagonia - Argentina. Relationship between the mineralogy and ceramic properties

International Nuclear Information System (INIS)

Factorovich, J.C.; Badino, D.; Cravero, F.; Dominguez, E.

1997-01-01

The mineralogy, grain size distribution, chemical composition, S and C contents, plasticity, and cationic exchange capacity are determined in the sedimentary kaolinitic clays from the clay pits Puma Negra, Puma Gris, Tincar Super; and Chenque and Cardenal located in Santa Cruz and Chubut Provinces. Mineralogy and Particle size distribution of > 5, 5-2 and <2μ fractions are determined. Modulus of rupture, 1100 and 1250 deg C shrinkage and water absorption and whiteness are found. It is accomplished a statistics correlation between the characteristics of grain size distribution, mineralogy, and other physical properties with the main ceramic properties to understand its influence in the ceramic process. (author)

7 CFR 1218.17 - Promotion.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1218.17 Section 1218.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion...

7 CFR 1219.22 - Promotion.

Science.gov (United States)

2010-01-01

... in the United States, including paid advertising, sales promotion, and publicity. Promotion... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1219.22 Section 1219.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH...

7 CFR 1215.16 - Promotion.

Science.gov (United States)

2010-01-01

... Promotion. Promotion means any action, including paid advertising, to enhance the image or desirability of... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1215.16 Section 1215.16 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND...

7 CFR 1160.111 - Promotion.

Science.gov (United States)

2010-01-01

... demand for fluid milk products. (b) Advertising, which means any advertising or promotion program... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1160.111 Section 1160.111 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order...

7 CFR 1230.22 - Promotion.

Science.gov (United States)

2010-01-01

... Promotion. Promotion means any action, including but not limited to paid advertising and retail or food... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1230.22 Section 1230.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...

Suppression of chondrosarcoma cells by 15-deoxy-Δ12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21

International Nuclear Information System (INIS)

Shen, Zheng-Nan; Nishida, Keiichiro; Doi, Hideyuki; Oohashi, Toshitaka; Hirohata, Satoshi; Ozaki, Toshifumi; Yoshida, Aki; Ninomiya, Yoshifumi; Inoue, Hajime

2005-01-01

We previously reported that 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), the most potent agonist for peroxisome proliferator-activated receptor γ (PPARγ), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ 2 -induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ 2 -induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ 2 , but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ 2 was partly, but not completely, blocked by PPARγ antagonist (GW9662) suggesting the 15d-PGJ 2 exerted its effect by PPARγ-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ 2 in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma

The impact of the distance-dependent promotional effect on the promotion cost sharing decision

Science.gov (United States)

Sheen, Gwo-Ji; Wang, Shih-Yen; Yeh, Yingchieh

2016-02-01

This paper considers the promotion cost sharing decision between a supplier and a retailer. The customer demand is affected by both national and local promotional effects while the local promotional effect on a customer is dependent on the distance between the retailer and this customer. We propose a continuous approximation approach to modelling the sum of the customer demand in the whole market area served by the retailer. A model is provided to help managers decide on the retail price, the local advertising expenditure, the national advertising expenditure, and the supplier participation rate, with consideration of the influence of distance on the promotional effect. We also find that the supplier's promotion cost sharing rate increases as the market size increases or the influence of distance on the promotional effect decreases. A numerical example is given to show that the nature of distance-dependent promotional effect has a significant impact on the decisions and profits.

Promoter And Duties And Responsibilities Of Promoters In English Company Law

OpenAIRE

Neval Okan

2003-01-01

Any person who does an act with reference to the formation of a company or in aid of its organization whether he has the intention to be a partners or not is a promoter. No statuory definition of promoter is given in English company law; definition is given in case law. Promoters stand in a fiduciary relation to the proposed company. Apromoter is not an agent for the company which he is forming because a company cannot have an agent before it comes into existence. The fiduciary duty is owed t...

Self-tracking as Health promotion

DEFF Research Database (Denmark)

Jelsøe, Erling

Self-tracking has become widespread in many parts of the world and is understood by many of its proponents as a way to obtain bodily control and through that to improve healthy living. As such self-tracking can be understood as a particular approach to practicing individual health promotion (even...... though this is not the only incentive for self-tracking). Even though health promotion is often seen as an activity, which resonates with a focus on individual responsibility, such a conception of health promotion contrasts with a broader critical concept of health promotion that emphasize social...... an analysis of social and community oriented dimensions of self-tracking as a form of health promotion compared to the above mentioned broad critical approach to health promotion in order to identify the contradictions as well as common traits and discuss implications for health promoting initiatives...

Tetrahydroxystilbene Glucoside Effectively Prevents Apoptosis Induced Hair Loss

Directory of Open Access Journals (Sweden)

Lulu Chen

2018-01-01

Full Text Available The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.

5 CFR 532.407 - Promotion.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Promotion. 532.407 Section 532.407... Administration § 532.407 Promotion. (a) An employee who is promoted is entitled to be paid at the lowest.... (c) If the promotion is to a position in a different wage area, the agency shall determine the...

MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis.

Science.gov (United States)

Xu, Longjiang; Leng, Hong; Shi, Xin; Ji, Jiang; Fu, Jinxiang; Leng, Hong

2017-06-01

MicroRNAs (miRNAs) have been demonstrated to contribute to malignant progression in psoriasis development. The purposes of the study was to evaluated the effects of miRNA-155 on cell proliferation, migration and apoptosis in psoriasis development via PTEN singaling pathway and identify its direct target protein. Quantitative real-time RT-PCR (qRT-PCR) was performed to examine the level of miR-155 in psoriasis cells, miR-155 was downregulated in a psoriasis cell line Hacat by transfected with small interfering RNA (siRNA), respectively. Cell survival was detected by the MTT assay and colony formation assay. Cell migration and invasion were measured via wound-healing assayand transwell assay. In addition, cell cycle and apoptosis about psoriasis cells was measured by flow cytometry. In this study, qRT-PCR assay showed that the expressions of miR-155 mRNA in psoriasis tissues were significantly higher than that in normal tissues. The assays about cell growth and proliferation showed that miR-155 knockdown led to a significant decrease in cell proliferation which was determined by MTT assay and colony formation assay compared to those of Lv-NC cells. Flow cytometry analysis showed that depletion of miR-155 could cause cell cycle change and the number of apoptotic cells was significantly increased in Lv-miR155 cells compared with control cells. In addition, the expression of several apoptosis-related factors were dramatically changed, such as PTEN, PIP 3 , AKT, p-AKT, Bax and Bcl-2. Our findings indicate that down-regulation of miR-155 significantly inhibits proliferation, migration, invasion and promotes apoptosis through PTEN singaling pathway in psoriasis cells. miR-155 might function as an oncogene miRNA in the progress of psoriasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

1800 MHz mobile phone irradiation induced oxidative and nitrosative stress leads to p53 dependent Bax mediated testicular apoptosis in mice, Mus musculus.

Science.gov (United States)

Shahin, Saba; Singh, Surya P; Chaturvedi, Chandra M

2018-09-01

Present study was carried out to investigate the effect of long-term mobile phone radiation exposure in different operative modes (Dialing, Receiving, and Stand-by) on immature male mice. Three-week old male mice were exposed to mobile phone (1800 MHz) radiation for 3 hr/day for 120 days in different operative modes. To check the changes/alteration in testicular histoarchitecture and serum testosterone level, HE staining and ELISA was performed respectively. Further, we have checked the redox status (ROS, NO, MDA level, and antioxidant enzymes: SOD, CAT, and GPx) by biochemical estimation, alteration in the expression of pro-apoptotic proteins (p53 and Bax), active executioner caspase-3, full length/uncleaved PARP-1 (DNA repair enzyme), anti-apoptotic proteins (Bcl-2 and Bcl-x L ) in testes by immunofluorescence and cytosolic cytochrome-c by Western blot. Decreased seminiferous tubule diameter, sperm count, and viability along with increased germ cells apoptosis and decreased serum testosterone level, was observed in the testes of all the mobile phone exposed mice compared with control. We also observed that, mobile phone radiation exposure in all the three different operative modes alters the testicular redox status via increasing ROS, NO, and MDA level, and decreasing antioxidant enzymes levels leading to enhanced apoptosis of testicular cells by increasing the expression of pro-apoptotic and apoptotic proteins along with decreasing the expression of anti-apoptotic protein. On the basis of results, it is conclude that long-term mobile phone radiation exposure induced oxidative stress leads to apoptosis of testicular cells and thus impairs testicular function. © 2018 Wiley Periodicals, Inc.

Mineralizations of the Lavalleja Group (Uruguay), a Probable Neoproterozoic Volcano-sedimentary Sequence

International Nuclear Information System (INIS)

Sanchez Bettucci, L.; Oyhantcabal, P.; Loureiro, J.; Basei, M.; Ramos, V.; Preciozzi, F.; Basei, M.

2004-01-01

The Lavalleja Group is located in the southern extreme of the Dom Feliciano Belt, being tentatively correlated with the Porongos and Brusque Groups of Brazil. The basement of the Lavalleja Group is probably represented by granitic gneissic rocks of the Campanero Unit with ages, in the southern portion, ranging from 1.75 to 2.1 Ga (U-Pb in zircon). The Lavalleja Group is characterized by narrow bands of meta sedimentary and meta volcanic rocks and it is separated in three formations, namely (from base to top): Zanja del Tigre, Fuente del Puma and Minas. Outcrops assigned to the Minas Formation have been recently correlated with the Arroyo del Soldado Group. Only the Fuente del Puma formation hosts base metals, Au and Ag occurrences. The Fuente del Puma formation is divided into three informal units: sedimentary, volcanic and hornblenditic gabbros. The sedimentary unit is characterized by an important amount of carbonates. Syn collisional to pos tectonic granitic bodies (Carapé Complex) intrudes the Lavalleja Group and the Campanero Unit. Several mineralizations are located in the Fuente del Puma Formation, those associated to Arrospide, Ramallo-Reus, Chape, Valencia, La Oriental, Apolonia, Redondo Hill, La China and La Paloma mines are the most important. In addition, many occurrences of Cu-Zn-Pb were recognized in the region. The Cu-Zn-Pb mineralization includes massive sulfides with pyrite-chalcopyrite-sphalerite-galena-pyrrothyte, arsenopyrite-hematite into small bodies with lenticular shape. The host rock shows frequently hydrothermal alteration. The geochemistry and the geological features of the mineralizations suggest Besshi Massive Sulphide Zn-Cu-Pb and SEDEX Zn-Pb as most probably genetic models for the deposits related to the Neoproterozoic orogeny. Early mineralizations are syngenetic and were formed on the sea floor, although the main mineralizations are related to remobilization during syn- to late-metamorphic events and thrusting

Camera traps as a tool for Carnivore conservation in a mosaic of Protected Areas in the Pantanal wetlands, Brazil

Directory of Open Access Journals (Sweden)

Grasiela Porfirio

2018-06-01

Full Text Available Although known globally for its biodiversity, only around 5% of the Brazilian Pantanal is protected. The Network for Protection and Conservation of Amolar Mountain Ridge is an informal initiative that legally protects over 2000 km2 of the Pantanal biome. Several camera-trapping surveys were carried out at Amolar Mountain Ridge from August 2011 to September 2013 in order to increase our knowledge of the species occurrence and its ecological requirements. The aims of this study were : 1 to inventory the carnivore species occurring within this network of protected areas; 2 to describe their activity patterns and 3 to discuss threats for those species' conservation in the region. We used the Kernel density method to describe the species' activity patterns. We obtained 764 records (from 12703 camera-days of eight carnivores, including endangered species in Brazil, such as the jaguar (Panthera onca, puma (Puma concolor, and ocelot (Leopardus pardalis, that were among the most frequently recorded by camera traps. The other species detected were the South America coati (Nasua nasua, the tayra (Eira barbara, the crab-eating raccoon (Procyon cancrivorus and the jaguarundi (Puma yagouaroundi. We provided information on activity patterns of the jaguar and puma, which exhibited cathemeral activity patterns, on the ocelot and crab-eating fox, which were mostly nocturnal, and on the Southern coati and jaguarundi, which were diurnal. Scansorial and species that occur naturally in low densities as the tayra and the crab-eating raccoon were difficult to be detected with the used camera trapping setting. However, due to the natural characteristics of the study area, camera trapping is among the most appropriate tools for providing data about carnivores and their prey. This information is essential to delineate conservation plans for Amolar Mountain Ridge.

Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients

Directory of Open Access Journals (Sweden)

Elainy Patricia Lino Gasparotto

2011-12-01

Full Text Available Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV. This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005. CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020; while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19 compared with controls (1.39 and 2.01, p=0.006 and p=0.020. CD34+ cells in PV patients showed an elevated Bid expression (14.4 in comparison with healthy subjects (1.0; p=0.002. Patients' leukocytes showed an A1 augmentation (7.41, p=0.001 and a reduced expression of Bax (0.19; p=0.040 and Bad (0.2; p=0.030. There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV. Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005. Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020 e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19 em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0

Employer and Promoter Perspectives on the Quality of Health Promotion Within the Healthy Workplace Accreditation.

Science.gov (United States)

Tung, Chen-Yin; Yin, Yun-Wen; Liu, Chia-Yun; Chang, Chia-Chen; Zhou, Yi-Ping

2017-07-01

To explore the employers' and promoters' perspective of health promotion quality according to the healthy workplace accreditation. We assessed the perspectives of 85 employers and 81 health promoters regarding the quality of health promotion at their workplaces. The method of measurement referenced the European Network for Workplace Health Promotion (ENWHP) quality criteria. In the large workplaces, the accredited corporation employers had a higher impression (P health promoters from different sized workplaces with or without accreditation (P > 0.05). It seems that employers' perspectives of healthy workplace accreditation surpassed employers from non-accredited workplaces. Specifically, large accredited corporations could share their successful experiences to encourage a more involved workplace in small-medium workplaces.

Engineered Promoters for Potent Transient Overexpression.

Directory of Open Access Journals (Sweden)

Dan Y Even

Full Text Available The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3, which combines four core promoter elements (the TATA box, Inr, MTE and DPE into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods.

Development of a promoter shutoff system in Aspergillus oryzae using a sorbitol-sensitive promoter.

Science.gov (United States)

Oda, Ken; Terado, Shiho; Toyoura, Rieko; Fukuda, Hisashi; Kawauchi, Moriyuki; Iwashita, Kazuhiro

2016-09-01

Promoter shutoff is a general method for analyzing essential genes, but in the fungus Aspergillus oryzae, no tightly repressed promoters have been reported. To overcome the current limitations of conditional promoters, we examined sorbitol- and galactose-responsive genes using microarrays to identify regulatable genes with only minor physiological and genetic effects. We identified two sorbitol-induced genes (designated as sorA and sorB), cloned their promoters, and built a regulated egfp and brlA expression system. Growth medium-dependent enhanced green fluorescence protein (EGFP) fluorescence and conidiation were confirmed for egfp and brlA under the control of their respective promoters. We also used this shutoff system to regulate the essential rhoA, which demonstrated the expected growth inhibition under repressed growth conditions. Our new sorbitol promoter shutoff system developed can serve as a valuable new tool for essential gene analyses of filamentous fungi.

3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

Energy Technology Data Exchange (ETDEWEB)

Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan, E-mail: moonsonlife@yahoo.com; Xian, Shulin; Lu, Yunfei, E-mail: doctorlife@126.com

2016-06-17

Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

International Nuclear Information System (INIS)

Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

2016-01-01

Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

29 CFR 541.503 - Promotion work.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Promotion work. 541.503 Section 541.503 Labor Regulations... Outside Sales Employees § 541.503 Promotion work. (a) Promotion work is one type of activity often.... Promotion activities directed toward consummation of the employee's own sales are exempt. Promotional...

The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters

DEFF Research Database (Denmark)

Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian

2011-01-01

Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... cloned into the promoter-probe plasmid pIJ487 just upstream of the promoter-less aphII gene that confers resistance to neomycin. This synthetic promoter library was transformed into Streptomyces lividans, and the resulting transformants were screened for their ability to grow in the presence of different...... projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters...

Distinct apoptotic blocks mediate resistance to panHER inhibitors in HER2+ breast cancer cells.

Science.gov (United States)

Karakas, Bahriye; Ozmay, Yeliz; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur

2018-05-04

Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2+ breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR-75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2+ breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Sales promotions and food consumption.

Science.gov (United States)

Hawkes, Corinna

2009-06-01

Sales promotions are widely used to market food to adults, children, and youth. Yet, in contrast to advertising, practically no attention has been paid to their impacts on dietary behaviors, or to how they may be used more effectively to promote healthy eating. This review explores the available literature on the subject. The objective is to identify if and what literature exists, examine the nature of this literature, and analyze what can be learned from it about the effects of sales promotions on food consumption. The review finds that while sales promotions lead to significant sales increases over the short-term, this does not necessarily lead to changes in food-consumption patterns. Nevertheless, there is evidence from econometric modeling studies indicating that sales promotions can influence consumption patterns by influencing the purchasing choices of consumers and encouraging them to eat more. These effects depend on the characteristics of the food product, sales promotion, and consumer. The complexity of the effects means that sales promotions aiming to encourage consumption of nutritious foods need to be carefully designed. These conclusions are based on studies that use mainly sales data as a proxy for dietary intake. The nutrition (and economics) research communities should add to this existing body of research to provide evidence on the impact of sales promotions on dietary intake and related behaviors. This would help support the development of a sales promotion environment conducive to healthy eating.

7 CFR 1220.121 - Promotion.

Science.gov (United States)

2010-01-01

... promotion means any action, including paid advertising, technical assistance, and trade servicing activities... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1220.121 Section 1220.121 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND...

Influence of 103Pd radioactive stent on apoptosis of vascular smooth muscle cells

International Nuclear Information System (INIS)

Liu Yingmei; Wu Wei; Chen Xiaochao; Zhang Xuming; Wang Jingfeng; Wei Yulin; Yang Li

2003-01-01

Objective: To evaluate the influence of 103 Pd radioactive stent on apoptosis and its relative genes bcl-2 and bax in injured vascular media smooth muscle cells of rabbit abdominal arteries and to investigate the mechanism of 103 Pd radioactive stent for preventing restenosis after angioplasty. Methods: Fifty male New Zealand rabbits were randomized into stent group and 103 Pd stent group. Each group was subdivided into 5 sub-groups. Control group was set up. The study arteries were harvested at 3, 7, 14, 28 and 56 d after stenting and the pathomorphology, apoptosis analysis and in situ hybridization were performed to evaluate the expression of bcl-2 and bax mRNA. Results: The severity of the restenosis in 103 Pd stent group was less than that of stent group. It was most obvious at the 56th day (P 103 Pd stent group had much more apoptosis of vascular smooth muscle cells than stent group did and reached the peak at the 7th day, (14.72±0.53)% vs (12.42±1.13)% (P 103 Pd stent group was much lower than that of stent group at 3 to 28 d. The difference was most obvious at the 28th day after stenting, (18.43± 0.67)% vs (21.55±0.93)% (P 103 Pd stent group was higher than that of stent group, the peak was at the 7th day, (11.17±0.94)% vs (9.30±1.01)%. The ratio of bcl-2/bax in 103 Pd stent group was much lower than that of stent group at 3 to 28 d. Linear correlation analysis showed that there was significant negative correlation between bcl-2 mRNA and apoptosis. Between bax mRNA and apoptosis, the positive correlation was found (P 103 Pd radioactive stent induced more significant apoptosis in vascular media smooth muscle cells by promoting the expression of apoptosis related genes and relieved the expanding of restenosis

A future task for health-promotion research: Integration of health promotion and sustainable development.

Science.gov (United States)

Jelsøe, Erling; Thualagant, Nicole; Holm, Jesper; Kjærgård, Bente; Andersen, Heidi Myglegård; From, Ditte-Marie; Land, Birgit; Pedersen, Kirsten Bransholm

2018-02-01

Based on previous studies and reflections collected from participants in a workshop at the 8th Nordic Health Promotion Research Network conference, we reveal current tendencies and discuss future challenges for health-promotion research regarding integration of sustainable development principles. Despite obvious interfaces and interactions between the two, our contention is that strategies for health promotion are not sufficiently integrated with strategies for sustainable development and that policies aimed at solving health or sustainability problems may therefore cause new, undesired and unforeseen environmental and health problems. As illustrated in previous research and as deliberated in the above-mentioned workshop, a number of barriers are identified. These are believed to be related to historical segregation, the conceptual understandings of health promotion and sustainable development, as well as the politics and implementation of policy goals in both areas. Three focal points are proposed as important challenges to address in future research: (a) the duality of health promotion and sustainability and how it can be handled in order to enhance mutually supportive processes between them; (b) the social dimension of sustainability and how it can be strengthened in the development of strategies for health promotion and sustainable development; and (c) exploring and identifying policy approaches and strategies for integrating health promotion and sustainable development.

Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors. Publishable Final Activity Report

International Nuclear Information System (INIS)

Kuijper, J.C.; Somers, J.; Van Den Durpel, L.

2013-01-01

The PUMA project - the acronym stands for “Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors” - was a Specific Targeted Research Project (STREP) within the Euratom 6th Framework (EU FP6). The PUMA project ran from September 1, 2006, until August 31, 2009, and was executed by a consortium of 14 European partner organisations and one from the USA. This report serves 2 purposes. It is both the 'Publishable Final Activity Report' and the 'Final (Summary) Report', describing, per Work Package, the specific objectives, research activities, main conclusions, recommendations and supporting documents. PUMA's main objective was to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO2-free energy generation. The PUMA project has assessed the impact of the introduction of Pu/MA-burning HTRs at three levels: fuel and fuel performance (modelling), reactor (transmutation performance and safety) and reactor/fuel cycle facility park. Earlier projects already indicated favourable characteristics of HTRs with respect to Pu burning. So, core physics of Pu/MA fuel cycles for HTRs has been investigated to study the CP fuel and reactor characteristics and to assure nuclear stability of a Pu/MA HTR core, under both normal and abnormal operating conditions. The starting point of this investigation comprised the two main contemporary HTR designs, viz. the pebble-bed type HTR, represented by the South-African PBMR, and hexagonal block type HTR, represented by the GT-MHR. The results (once again) demonstrate the flexibility of the contemporary (and near future) HTR designs and their ability to accept a variety

Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors. Publishable Final Activity Report

International Nuclear Information System (INIS)

Kuijper, J.C.; Somers, J.; Van Den Durpel, L.; Chauvet, V.; Cerullo, N.; Cetnar, J.; Abram, T.; Bakker, K.; Bomboni, E.; Bernnat, W.; Domanska, J.G.; Girardi, E.; De Haas, J.B.M.; Hesketh, K.; Hiernaut, J.P.; Hossain, K.; Jonnet, J.; Kim, Y.; Kloosterman, J.L.; Kopec, M.; Murgatroyd, J.; Millington, D.; Lecarpentier, D.; Lomonaco, G.; McEachern, D.; Meier, A.; Mignanelli, M.; Nabielek, H.; Oppe, J.; Petrov, B.Y.; Pohl, C.; Ruetten, H.J.; Schihab, S.; Toury, G.; Trakas, C.; Venneri, F.; Verfondern, K.; Werner, H.; Wiss, T.; Zakova, J.

2010-11-01

The PUMA project -the acronym stands for 'Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors'- was a Specific Targeted Research Project (STREP) within the EURATOM 6th Framework Program (EU FP6). The PUMA project ran from September 1, 2006, until August 31, 2009, and was executed by a consortium of 14 European partner organisations and one from the USA. This report serves 2 purposes. It is both the 'Publishable Final Activity Report' and the 'Final (Summary) Report', describing, per Work Package, the specific objectives, research activities, main conclusions, recommendations and supporting documents. PUMA's main objective was to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO 2 -free energy generation. The PUMA project has assessed the impact of the introduction of Pu/MA-burning HTRs at three levels: fuel and fuel performance (modelling), reactor (transmutation performance and safety) and reactor/fuel cycle facility park. Earlier projects already indicated favourable characteristics of HTRs with respect to Pu burning. So, core physics of Pu/MA fuel cycles for HTRs has been investigated to study the CP fuel and reactor characteristics and to assure nuclear stability of a Pu/MA HTR core, under both normal and abnormal operating conditions. The starting point of this investigation comprised the two main contemporary HTR designs, viz. the pebble-bed type HTR, represented by the South-African PBMR, and hexagonal block type HTR, represented by the GT-MHR. The results (once again) demonstrate the flexibility of the contemporary (and near future) HTR designs and their ability to accept a

Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors. Publishable Final Activity Report

Energy Technology Data Exchange (ETDEWEB)

Kuijper, J.C., E-mail: kuijper@nrg.eu [Nuclear Research and Consultancy Group (NRG), Petten (Netherlands); Somers, J; Van Den Durpel, L; Chauvet, V; Cerullo, N; Cetnar, J; Abram, T; Bakker, K; Bomboni, E; Bernnat, W; Domanska, J G; Girardi, E; De Haas, J B.M.; Hesketh, K; Hiernaut, J P; Hossain, K; Jonnet, J; Kim, Y; Kloosterman, J L; Kopec, M; Murgatroyd, J; Millington, D; Lecarpentier, D; Lomonaco, G; McEachern, D; Meier, A; Mignanelli, M; Nabielek, H; Oppe, J; Petrov, B Y; Pohl, C; Ruetten, H J; Schihab, S; Toury, G; Trakas, C; Venneri, F; Verfondern, K; Werner, H; Wiss, T; Zakova, J

2010-11-15

The PUMA project -the acronym stands for 'Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors'- was a Specific Targeted Research Project (STREP) within the EURATOM 6th Framework Program (EU FP6). The PUMA project ran from September 1, 2006, until August 31, 2009, and was executed by a consortium of 14 European partner organisations and one from the USA. This report serves 2 purposes. It is both the 'Publishable Final Activity Report' and the 'Final (Summary) Report', describing, per Work Package, the specific objectives, research activities, main conclusions, recommendations and supporting documents. PUMA's main objective was to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO{sub 2}-free energy generation. The PUMA project has assessed the impact of the introduction of Pu/MA-burning HTRs at three levels: fuel and fuel performance (modelling), reactor (transmutation performance and safety) and reactor/fuel cycle facility park. Earlier projects already indicated favourable characteristics of HTRs with respect to Pu burning. So, core physics of Pu/MA fuel cycles for HTRs has been investigated to study the CP fuel and reactor characteristics and to assure nuclear stability of a Pu/MA HTR core, under both normal and abnormal operating conditions. The starting point of this investigation comprised the two main contemporary HTR designs, viz. the pebble-bed type HTR, represented by the South-African PBMR, and hexagonal block type HTR, represented by the GT-MHR. The results (once again) demonstrate the flexibility of the contemporary (and near future) HTR designs and their ability to accept a

Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors. Publishable Final Activity Report

Energy Technology Data Exchange (ETDEWEB)

Kuijper, J.C., E-mail: kuijper@nrg.eu [Nuclear Research and Consultancy Group (NRG), Petten (Netherlands); Somers, J.; Van Den Durpel, L.; Chauvet, V.; Cerullo, N.; Cetnar, J.; Abram, T.; Bakker, K.; Bomboni, E.; Bernnat, W.; Domanska, J.G.; Girardi, E.; De Haas, J.B.M.; Hesketh, K.; Hiernaut, J.P.; Hossain, K.; Jonnet, J.; Kim, Y.; Kloosterman, J.L.; Kopec, M.; Murgatroyd, J.; Millington, D.; Lecarpentier, D.; Lomonaco, G.; McEachern, D.; Meier, A.; Mignanelli, M.; Nabielek, H.; Oppe, J.; Petrov, B.Y.; Pohl, C.; Ruetten, H.J.; Schihab, S.; Toury, G.; Trakas, C.; Venneri, F.; Verfondern, K.; Werner, H.; Wiss, T.; Zakova, J.

2010-11-15

The PUMA project -the acronym stands for 'Plutonium and Minor Actinide Management in Thermal High-Temperature Gas-Cooled Reactors'- was a Specific Targeted Research Project (STREP) within the EURATOM 6th Framework Program (EU FP6). The PUMA project ran from September 1, 2006, until August 31, 2009, and was executed by a consortium of 14 European partner organisations and one from the USA. This report serves 2 purposes. It is both the 'Publishable Final Activity Report' and the 'Final (Summary) Report', describing, per Work Package, the specific objectives, research activities, main conclusions, recommendations and supporting documents. PUMA's main objective was to investigate the possibilities for the utilisation and transmutation of plutonium and especially minor actinides in contemporary and future (high temperature) gas-cooled reactor designs, which are promising tools for improving the sustainability of the nuclear fuel cycle. This contributes to the reduction of Pu and MA stockpiles, and also to the development of safe and sustainable reactors for CO{sub 2}-free energy generation. The PUMA project has assessed the impact of the introduction of Pu/MA-burning HTRs at three levels: fuel and fuel performance (modelling), reactor (transmutation performance and safety) and reactor/fuel cycle facility park. Earlier projects already indicated favourable characteristics of HTRs with respect to Pu burning. So, core physics of Pu/MA fuel cycles for HTRs has been investigated to study the CP fuel and reactor characteristics and to assure nuclear stability of a Pu/MA HTR core, under both normal and abnormal operating conditions. The starting point of this investigation comprised the two main contemporary HTR designs, viz. the pebble-bed type HTR, represented by the South-African PBMR, and hexagonal block type HTR, represented by the GT-MHR. The results (once again) demonstrate the flexibility of the contemporary (and near future) HTR

Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis.

Science.gov (United States)

Kim, Dongjoon; Mecham, Robert P; Trackman, Philip C; Roy, Sayon

2017-05-01

To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor. LOX expression, AKT activation, and caspase-3 activity were determined by Western blot (WB) analysis and apoptosis by differential dye staining assay. Moreover, to determine whether diabetes-induced LOX overexpression alters AKT activation and promotes apoptosis, changes in LOX expression, AKT phosphorylation, caspase-3 activation, and Bax expression were assessed in retinas of streptozotocin (STZ)-induced diabetic mice and LOX heterozygous knockout (LOX+/-) mice. WB analysis indicated significant LOX overexpression and reduced AKT activation under HG condition in RRECs. Interestingly, when cells grown in HG were transfected with LOX siRNA or exposed to BAPN, the number of apoptotic cells was significantly decreased concomitant with increased AKT phosphorylation. Diabetic mouse retinas exhibited LOX overexpression, decreased AKT phosphorylation, and increased Bax and caspase-3 activation compared to values in nondiabetic mice. In LOX+/- mice, reduced LOX levels were observed with increased AKT activity, and reduced Bax and caspase-3 activity. Furthermore, decreased levels of LOX in the LOX+/- mice was protective against diabetes-induced apoptosis. Findings from this study indicate that preventing LOX overexpression may be protective against HG-induced apoptosis in retinal vascular cells associated with diabetic retinopathy.

Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Yao, Jingyun; Wei, Xing [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai (China); Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai (China); Lu, Yanhua, E-mail: luyanhua@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai (China); Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai (China)

2016-05-13

Drug resistance limits leukemia treatment and chaetominine, a cytotoxic alkaloid that promotes apoptosis in a K562 human leukemia cell line via the mitochondrial pathway was studied with respect to chemoresistance in a K562/Adr human resistant leukemia cell line. Cytotoxicity assays indicated that K562/Adr resistance to adriamycin (ADR) did not occur in the presence of chaetominine and that chaetominine increased chemosensitivity of K562/Adr to ADR. Data show that chaetominine enhanced ADR-induced apoptosis and intracellular ADR accumulation in K562/Adr cells. Accordingly, chaetominine induced apoptosis by upregulating ROS, pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2. RT-PCR and western-blot confirmed that chaetominine suppressed highly expressed MRP1 at mRNA and protein levels. But little obvious alternation of another drug transporter MDR1 mRNA was observed. Furthermore, inhibition of MRP1 by chaetominine relied on inhibiting Akt phosphorylation and nuclear Nrf2. In summary, chaetominine strongly reverses drug resistance by interfering with the PI3K/Akt/Nrf2 signaling, resulting in reduction of MRP1-mediated drug efflux and induction of Bax/Bcl-2-dependent apoptosis in an ADR-resistant K562/Adr leukemia cell line. - Highlights: • Chaetominine enhanced chemosensitivity of ADR against K562/Adr cells. • Chaetominine increased intracellular ADR levels via inhibiting MRP1. • Chaetominine induced apoptosis of K562/Adr cells through upregulation of ROS and modulation of Bax/Bcl-2. • Inhibition of MRP1 and Nrf2 by chaetominine treatment was correlative with blockade of PI3K/Akt signaling.

Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage

Science.gov (United States)

Mihaylova, Valia T.; Green, Allison M.; Khurgel, Moshe; Semmes, Oliver J.; Kupfer, Gary M.

2018-01-01

Mutations in p53 are a common cause of resistance of cancers to standard chemotherapy and, thus, treatment failure. Reports have shown that Tax, a human T-cell leukemia virus type I encoded protein that has been associated with genomic instability and perturbation of transcription and cell cycle, sensitizes HeLa cells to UV treatment. The extent to which Tax can sensitize cells and the mechanism by which it exerts its effect are unknown. In this study, we show that Tax sensitizes p53-mutant cells to a broad range of DNA-damaging agents, including mitomycin C, a bifunctional alkylator, etoposide, a topoisomerase II drug, and UV light, but not ionizing radiation, a double-strand break agent, or vinblastine, a tubulin poison. Tax caused hypersensitivity in all p53-deleted cell lines and several, but not all, mutant-expressed p53–containing cell lines, while unexpectedly being protective in p53 wild-type (wt) cells. The effect observed in p53-deleted lines could be reversed for this by transfection of wt p53. We also show that Tax activates a p53-independent proapoptotic program through decreased expression of the retinoblastoma protein and subsequent increased E2F1 expression. The expression of several proapoptotic proteins was also induced by Tax, including Puma and Noxa, culminating in a substantial increase in Bax dimerization. Our results show that Tax can sensitize p53-mutant cells to DNA damage while protecting p53 wt cells, a side benefit that might result in reduced toxicity in normal cells. Such studies hold the promise of a novel adjunctive therapy that could make cancer chemotherapy more effective. PMID:18559532

Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

Directory of Open Access Journals (Sweden)

Louis Chesler

2008-11-01

Full Text Available Chemoresistance in neuroblastoma is a significant issue complicating treatment of this common pediatric solid tumor. MYCN-amplified neuroblastomas are infrequently mutated at p53 and are chemosensitive at diagnosis but acquire p53 mutations and chemoresistance with relapse. Paradoxically, Myc-driven transformation is thought to require apoptotic blockade. We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy. Tumors formed with high penetrance and low latency in p53-haploinsufficient TH-MYCN mice. Cyclophosphamide (CPM induced a complete remission in p53 wild type TH-MYCN tumors, mirroring the sensitivity of childhood neuroblastoma to this agent. Treated tumors showed a prominent proliferation block, induction of p53 protein, and massive apoptosis proceeding through induction of the Bcl-2 homology domain-3-only proteins PUMA and Bim, leading to the activation of Bax and cleavage of caspase-3 and -9. Apoptosis induced by CPM was reduced in p53-haploinsufficient tumors. Treatment of MYCN-expressing human neuroblastoma cell lines with CPM induced apoptosis that was suppressible by siRNA to p53. Taken together, the results indicate that the p53 pathway plays a significant role in opposing MYCN-driven oncogenesis in a mouse model of neuroblastoma and that basal inactivation of the pathway is achieved in progressing tumors. This, in part, explains the striking sensitivity of such tumors to chemotoxic agents that induce p53-dependent apoptosis and is consistent with clinical observations that therapy-associated mutations in p53 are a likely contributor to the biology of tumors at relapse and secondarily mediate resistance to therapy.

Melatonin Reverses Fas, E2F-1 and Endoplasmic Reticulum Stress Mediated Apoptosis and Dysregulation of Autophagy Induced by the Herbicide Atrazine in Murine Splenocytes.

Directory of Open Access Journals (Sweden)

Shweta Sharma

Full Text Available Exposure to the herbicide Atrazine (ATR can cause immunotoxicity, apart from other adverse consequences for animal and human health. We aimed at elucidating the apoptotic mechanisms involved in immunotoxicity of ATR and their attenuation by Melatonin (MEL. Young Swiss mice were divided into control, ATR and MEL+ATR groups based on daily (x14 intraperitoneal administration of the vehicle (normal saline, ATR (100 mg/kg body weight and MEL (20 mg/kg body weight with ATR. Isolated splenocytes were processed for detection of apoptosis by Annexin V-FITC and TUNEL assays, and endoplasmic reticulum (ER stress by immunostaining. Key proteins involved in apoptosis, ER stress and autophagy were quantified by immunoblotting. ATR treatment resulted in Fas-mediated activation of caspases 8 and 3 and inactivation of PARP1 which were inhibited significantly by co-treatment with MEL. MEL also attenuated the ATR-induced, p53 independent mitochondrial apoptosis through upregulation of E2F-1 and PUMA and suppression of their downstream target Bax. An excessive ER stress triggered by ATR through overexpression of ATF-6α, spliced XBP-1, CREB-2 and GADD153 signals was reversed by MEL. MEL also reversed the ATR-induced impairment of autophagy which was indicated by a decline in BECN-1, along with significant enhancement in LC3B-II and p62 expressions. Induction of mitochondrial apoptosis, ER stress and autophagy dysregulation provide a new insight into the mechanism of ATR immunotoxicity. The cytoprotective role of MEL, on the other hand, was defined by attenuation of ER stress, Fas-mediated and p53 independent mitochondria-mediated apoptosis as well as autophagy signals.

Health promotion in the workplace

Directory of Open Access Journals (Sweden)

Sultan T Al-Otaibi

2016-01-01

Full Text Available The objective of this review was to describe the scientific evidence for coordinating health promotion at the workplace and to discuss the required future research in this field. Literature review from March 1990 to November 2014 was performed. Using the keywords ′health, promotion, worksite and workplace′, literature was searched in the following databases: Medline, PubMed and Google Scholar; with no time limit. There is emerging evidence that workplace health promotion enhances the effectiveness of effort to promote and protect workers′ health. It proves both cost-effective and cost-beneficial to health promotion at the worksite and subsequently further reduces absenteeism. However, future research is needed to identify the impact of other factors such as age, gender and race on workers′ exposure. There is also a need to develop valid tests to measure the outcome of these programmes at the workplace. Health promotion should be central to workplace planning and should be recognised as an integral part of proactive occupational health. Indeed, the workplace is viewed as one of the most popular venues for promoting health and preventing diseases among employees.

Assessing environmental assets for health promotion program planning: a practical framework for health promotion practitioners.

Science.gov (United States)

Springer, Andrew E; Evans, Alexandra E

2016-01-01

Conducting a health needs assessment is an important if not essential first step for health promotion planning. This paper explores how health needs assessments may be further strengthened for health promotion planning via an assessment of environmental assets rooted in the multiple environments (policy, information, social and physical environments) that shape health and behavior. Guided by a behavioral-ecological perspective- one that seeks to identify environmental assets that can influence health behavior, and an implementation science perspective- one that seeks to interweave health promotion strategies into existing environmental assets, we present a basic framework for assessing environmental assets and review examples from the literature to illustrate the incorporation of environmental assets into health program design. Health promotion practitioners and researchers implicitly identify and apply environmental assets in the design and implementation of health promotion interventions;this paper provides foundation for greater intentionality in assessing environmental assets for health promotion planning.

Melatonin promotes Bax sequestration to mitochondria reducing cell susceptibility to apoptosis via the lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid

KAUST Repository

Radogna, Flavia; Albertini, M. C.; De Nicola, Milena D.; Diederich, Marc; Bejarano, Ignacio; Ghibelli, Lina

2015-01-01

of melatonin binding to its low affinity target calmodulin. Therefore, the anti-apoptotic effect of melatonin requires the simultaneous, independent interaction with high (MT1/MT2) and low (calmodulin) affinity targets, eliciting two independent signal

Alcohol promotions in Australian supermarket catalogues.

Science.gov (United States)

Johnston, Robyn; Stafford, Julia; Pierce, Hannah; Daube, Mike

2017-07-01

In Australia, most alcohol is sold as packaged liquor from off-premises retailers, a market increasingly dominated by supermarket chains. Competition between retailers may encourage marketing approaches, for example, discounting, that evidence indicates contribute to alcohol-related harms. This research documented the nature and variety of promotional methods used by two major supermarket retailers to promote alcohol products in their supermarket catalogues. Weekly catalogues from the two largest Australian supermarket chains were reviewed for alcohol-related content over 12 months. Alcohol promotions were assessed for promotion type, product type, number of standard drinks, purchase price and price/standard drink. Each store catalogue included, on average, 13 alcohol promotions/week, with price-based promotions most common. Forty-five percent of promotions required the purchase of multiple alcohol items. Wine was the most frequently promoted product (44%), followed by beer (24%) and spirits (18%). Most (99%) wine cask (2-5 L container) promotions required multiple (two to three) casks to be purchased. The average number of standard drinks required to be purchased to participate in catalogue promotions was 31.7 (SD = 24.9; median = 23.1). The median price per standard drink was $1.49 (range $0.19-$9.81). Cask wines had the lowest cost per standard drink across all product types. Supermarket catalogues' emphasis on low prices/high volumes of alcohol reflects that retailers are taking advantage of limited restrictions on off-premise sales and promotion, which allow them to approach market competition in ways that may increase alcohol-related harms in consumers. Regulation of alcohol marketing should address retailer catalogue promotions. [Johnston R, Stafford J, Pierce H, Daube M. Alcohol promotions in Australian supermarket catalogues. Drug Alcohol Rev 2017;36:456-463]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

78 FR 24239 - Temporary Mailing Promotion

Science.gov (United States)

2013-04-24

... POSTAL REGULATORY COMMISSION [Docket No. R2013-6; Order No. 1702] Temporary Mailing Promotion... offering a Technology Credit Promotion. This notice informs the public of the Postal Service's filing and... changes associated with offering a Technology Credit Promotion.\\1\\ The promotion is planned to begin on...

Measuring the Cost of Supermarket Promotions

DEFF Research Database (Denmark)

Gao, Cixiu

2014-01-01

The widespread use of retail promotions and the magnitude of dollars spent on them call economists to examine the role of promotional costs in shaping the coordination of pricing and promotion decisions. In this study, I estimate the marginal cost of price promotion in the retail industry. The es...

Proliferating Cell Nuclear Antigen (PCNA) Regulates Primordial Follicle Assembly by Promoting Apoptosis of Oocytes in Fetal and Neonatal Mouse Ovaries

Science.gov (United States)

Zhang, Yuanwei; Jiang, Xiaohua; Zhang, Huan; Ma, Tieliang; Zheng, Wei; Sun, Rui; Shen, Wei; Sha, Jiahao; Cooke, Howard J.; Shi, Qinghua

2011-01-01

Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer guanulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. PMID:21253613

Proliferating cell nuclear antigen (PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

Directory of Open Access Journals (Sweden)

Bo Xu

Full Text Available Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA, a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer granulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

Information technology in health promotion.

Science.gov (United States)

Lintonen, T P; Konu, A I; Seedhouse, D

2008-06-01

eHealth, the use of information technology to improve or enable health and health care, has recently been high on the health care development agenda. Given the vivid interest in eHealth, little reference has been made to the use of these technologies in the promotion of health. The aim of this present study was to conduct a review on recent uses of information technology in health promotion through looking at research articles published in peer-reviewed journals. Fifteen relevant journals with issues published between 2003 and June 2005 yielded altogether 1352 articles, 56 of which contained content related to the use of information technology in the context of health promotion. As reflected by this rather small proportion, research on the role of information technology is only starting to emerge. Four broad thematic application areas within health promotion were identified: use of information technology as an intervention medium, use of information technology as a research focus, use of information technology as a research instrument and use of information technology for professional development. In line with this rather instrumental focus, the concepts 'ePromotion of Health' or 'Health ePromotion' would come close to describing the role of information technology in health promotion.

76 FR 26930 - Dairy Promotion and Research Program; Importer Nominations to the Dairy Promotion and Research Board

Science.gov (United States)

2011-05-10

...: AMS-DA-08-0050] Dairy Promotion and Research Program; Importer Nominations to the Dairy Promotion and... to the Dairy Production Stabilization Act of 1983 (Dairy Act), as amended, and the Dairy Promotion... importer representation, initially two members, to the National Dairy Promotion and Research Board (Dairy...

Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

Science.gov (United States)

Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

2013-11-01

Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

Effect of dentate gyrus disruption on remembering what happened where

Directory of Open Access Journals (Sweden)

Min W Jung

2015-06-01

Full Text Available Our previous studies using Bax knockout (Bax-KO mice, in which newly generated granule cells continue to accumulate, disrupting neural circuitry specifically in the dentate gyrus (DG, suggest the involvement of the DG in binding the internally-generated spatial map with sensory information on external landmarks (spatial map-object association in forming a distinct spatial context for each environment. In order to test whether the DG is also involved in binding the internal spatial map with sensory information on external events (spatial map-event association, we tested the behavior of Bax-KO mice in a delayed-non-match-to-place task. Performance of Bax-KO mice was indistinguishable from that of wild-type mice as long as there was no interruption during the delay period (tested up to 5 min, suggesting that on-line maintenance of working memory is intact in Bax-KO mice. However, Bax-KO mice showed profound performance deficits when they were removed from the maze during the delay period (interruption condition with a sufficiently long (65 s delay, suggesting that episodic memory was impaired in Bax-KO mice. Together with previous findings, these results suggest the role of the DG in binding spatial information derived from dead reckoning and nonspatial information, such as external objects and events, in the process of encoding episodic memory.

A Menagerie of Promotional Characters: Promoting Food to Children through Food Packaging

Science.gov (United States)

Hebden, Lana; King, Lesley; Kelly, Bridget; Chapman, Kathy; Innes-Hughes, Christine

2011-01-01

Objective: To determine the extent to which (1) promotional characters are used on food packaging for healthful and less-healthful food and (2) different companies use this persuasive marketing strategy. Design: Cross-sectional supermarket audit of all food and beverages featuring promotional characters on the packaging. Setting: Three Australian…

Health promotion: an ethical analysis.

Science.gov (United States)

Carter, Stacy M

2014-04-01

Thinking and practising ethically requires reasoning systematically about the right thing to do. Health promotion ethics - a form of applied ethics - includes analysis of health promotion practice and how this can be ethically justified. Existing frameworks can assist in such evaluation. These acknowledge the moral value of delivering benefits. But benefits need to be weighed against burdens, harms or wrongs, and these should be minimised: they include invading privacy, breaking confidentiality, restraining liberty, undermining self-determination or people's own values, or perpetuating injustice. Thinking about the ethics of health promotion also means recognising health promotion as a normative ideal: a vision of the good society. This ideal society values health, sees citizens as active and includes them in decisions that affect them, and makes the state responsible for providing all of its citizens, no matter how advantaged or disadvantaged, with the conditions and resources they need to be healthy. Ethicists writing about health promotion have focused on this relationship between the citizen and the state. Comparing existing frameworks, theories and the expressed values of practitioners themselves, we can see common patterns. All oppose pursuing an instrumental, individualistic, health-at-all-costs vision of health promotion. And all defend the moral significance of just processes: those that engage with citizens in a transparent, inclusive and open way. In recent years, some Australian governments have sought to delegitimise health promotion, defining it as extraneous to the role of the state. Good evidence is not enough to counter this trend, because it is founded in competing visions of a good society. For this reason, the most pressing agenda for health promotion ethics is to engage with communities, in a procedurally just way, about the role and responsibilities of the citizen and the state in promoting and maintaining good health.

Marketing instruments of foreign trade promotion

Directory of Open Access Journals (Sweden)

Bjelić Predrag

2011-01-01

Full Text Available Instruments of promotion as a part of marketing mix are usually associated with companies but more and more countries use this instrument in order to boost their exports. These foreign trade promotion instruments are now popular in many countries in the world since their use is not opposed to any World Trade Organization rules. Marketing instruments of trade promotions are the most important. They include National Exhibitions and National labels of origin and quality. In order to coordinate the application of these instruments countries have established national bodies for trade promotion. Many studies in the past had argued that national Agencies established to promote export did not had any real success, but recent studies indicate that they could have a significant impact on country export promotion. The result of this rise in impact of national export promotion agencies is due to international effort spearheaded by International Trade Center. The aim of this paper is to point out types and methods of marketing instruments application in trade promotion and to present the effectiveness of these instruments applications.

Promoter reuse in prokaryotes