Science.gov

Sample records for light-induced survival response

  1. UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

    SciTech Connect

    Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

    1982-02-01

    A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance after ..gamma..-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process.

  2. Differential Light-induced Responses in Sectorial Inherited Retinal Degeneration*

    PubMed Central

    Ramon, Eva; Cordomí, Arnau; Aguilà, Mònica; Srinivasan, Sundaramoorthy; Dong, Xiaoyun; Moore, Anthony T.; Webster, Andrew R.; Cheetham, Michael E.; Garriga, Pere

    2014-01-01

    Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous inherited degenerative retinopathies caused by abnormalities of photoreceptors or retinal pigment epithelium in the retina leading to progressive sight loss. Rhodopsin is the prototypical G-protein-coupled receptor located in the vertebrate retina and is responsible for dim light vision. Here, novel M39R and N55K variants were identified as causing an intriguing sector phenotype of RP in affected patients, with selective degeneration in the inferior retina. To gain insights into the molecular aspects associated with this sector RP phenotype, whose molecular mechanism remains elusive, the mutations were constructed by site-directed mutagenesis, expressed in heterologous systems, and studied by biochemical, spectroscopic, and functional assays. M39R and N55K opsins had variable degrees of chromophore regeneration when compared with WT opsin but showed no gross structural misfolding or altered trafficking. M39R showed a faster rate for transducin activation than WT rhodopsin with a faster metarhodopsinII decay, whereas N55K presented a reduced activation rate and an altered photobleaching pattern. N55K also showed an altered retinal release from the opsin binding pocket upon light exposure, affecting its optimal functional response. Our data suggest that these sector RP mutations cause different protein phenotypes that may be related to their different clinical progression. Overall, these findings illuminate the molecular mechanisms of sector RP associated with rhodopsin mutations. PMID:25359768

  3. Photochemically triggered cytosolic drug delivery using pH-responsive hyaluronic acid nanoparticles for light-induced cancer therapy.

    PubMed

    Lee, Chung-Sung; Na, Kun

    2014-11-10

    A photochemically triggered cytosolic drug delivery system based on combining tumor-targeting pH-responsive hyaluronic acid (HA) nanoparticles (PHANs) with anticancer therapeutics (doxorubicin; DOX) was successfully developed for light-induced cancer therapy. PHANs were prepared through the self-assembly of a photosensitizer (PS), chlorin e6, and a pH-responsive moiety, poly(diisopropylaminoethyl) aspartamide (PDIPASP),conjugated to HA. DOX encapsulating PHANs (DOX@PHANs) have a uniform spherical shape,a sub-100 nm size distribution and a negative surface charge. The pH-responsiveness of PHANs leads to their disassembly due to the protonation of PDIPASP, which triggers DOX release. Competitive cellular uptake and confocal microscopy studies revealed CD44 receptor-mediated endocytosis, endosomal escape capability and efficient drug targeting. Compared to treatment with free DOX or PHANs, the combined treatment with DOX@PHANs and spatiotemporally defined irradiation remarkably improved the anticancer efficacy both in vitro and in vivo studies. Therefore, this strategy shows promise for the photochemically triggered cytosolic drug delivery of therapeutic agents for light-induced cancer therapy. PMID:25251731

  4. Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response

    PubMed Central

    Randhawa, Manpreet; Seo, InSeok; Liebel, Frank; Southall, Michael D.; Kollias, Nikiforos; Ruvolo, Eduardo

    2015-01-01

    Visible light (400–700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions. PMID:26121474

  5. Effects of kinetics of light-induced stomatal responses on photosynthesis and water-use efficiency.

    PubMed

    McAusland, Lorna; Vialet-Chabrand, Silvère; Davey, Philip; Baker, Neil R; Brendel, Oliver; Lawson, Tracy

    2016-09-01

    Both photosynthesis (A) and stomatal conductance (gs ) respond to changing irradiance, yet stomatal responses are an order of magnitude slower than photosynthesis, resulting in noncoordination between A and gs in dynamic light environments. Infrared gas exchange analysis was used to examine the temporal responses and coordination of A and gs to a step increase and decrease in light in a range of different species, and the impact on intrinsic water use efficiency was evaluated. The temporal responses revealed a large range of strategies to save water or maximize photosynthesis in the different species used in this study but also displayed an uncoupling of A and gs in most of the species. The shape of the guard cells influenced the rapidity of response and the overall gs values achieved, with different impacts on A and Wi . The rapidity of gs in dumbbell-shaped guard cells could be attributed to size, whilst in elliptical-shaped guard cells features other than anatomy were more important for kinetics. Our findings suggest significant variation in the rapidity of stomatal responses amongst species, providing a novel target for improving photosynthesis and water use. PMID:27214387

  6. Functional characterization of blue-light-induced responses and PHOTOTROPIN 1 gene in Welwitschia mirabilis.

    PubMed

    Ishishita, Kazuhiro; Suetsugu, Noriyuki; Hirose, Yuki; Higa, Takeshi; Doi, Michio; Wada, Masamitsu; Matsushita, Tomonao; Gotoh, Eiji

    2016-03-01

    The blue light (BL) receptor phototropin (phot) is specifically found in green plants; it regulates various BL-induced responses such as phototropism, chloroplast movement, stomatal opening, and leaf flattening. In Arabidopsis thaliana, two phototropins--phot1 and phot2--respond to blue light in overlapping but distinct ways. These BL-receptor-mediated responses enhance the photosynthetic activity of plants under weak light and minimize photodamage under strong light conditions. Welwitschia mirabilis Hook.f. found in the Namib Desert, and it has adapted to severe environmental stresses such as limiting water and strong sunlight. Although the plant has physiologically and ecologically unique features, it is unknown whether phototropin is functional in this plant. In this study, we assessed the functioning of phot-mediated BL responses in W. mirabilis. BL-dependent phototropism and stomatal opening was observed but light-dependent chloroplast movement was not detected. We performed a functional analysis of the PHOT1 gene of W. mirabilis, WmPHOT1, in Arabidopsis thaliana. We generated transgenic A. thaliana lines expressing WmPHOT1 in a phot1 phot2 double mutant background. Several Wmphot1 transgenic plants showed normal growth, although phot1 phot2 double mutant plants showed stunted growth. Furthermore, Wmphot1 transgenic plants showed normal phot1-mediated responses including phototropism, chloroplast accumulation, stomatal opening, and leaf flattening, but lacked the chloroplast avoidance response that is specifically mediated by phot2. Thus, our findings indicate that W. mirabilis possesses typical phot-mediated BL responses that were at least partially mediated by functional phototropin 1, an ortholog of Atphot1. PMID:26858202

  7. The different response mechanisms of Wolffia globosa: Light-induced silver nanoparticle toxicity.

    PubMed

    Zou, Xiaoyan; Li, Penghui; Huang, Qing; Zhang, Hongwu

    2016-07-01

    Silver nanoparticles (AgNPs) have emerged as a promising bactericide. Plants are a major point of entry of contaminants into trophic chains. Here, the physiological responses of Wolffia globosa to AgNPs have been probed using different light schemes, and these data may reveal new insights into the toxic mechanism of AgNPs. W. globosa was grown in culture medium and treated with different concentrations of AgNPs for 24h under pre- and post-illuminated conditions. However, fluorescence quenching, the accumulation of sugar and the reduction of Hill reaction activity were found in response to the AgNP-stresses. In the pre-illuminated condition, oxidative damage was obvious, as indicated by the higher malondialdehyde (MDA) content and an up-regulation of superoxide dismutase (SOD) activity. The maximum increases of MDA content and SOD activity were 1.14 and 2.52 times the respective controls when exposed to 10mg/L AgNPs. In contrast, in the post-illuminated condition, the alterations in photosynthetic pigment and soluble proteins content were more significant than the alterations in oxidative stress. The contents of chlorophyll a, carotenoids and soluble protein decreased to 77.7%, 66.2% and 72.9% of the controls after treatment with the highest concentration of AgNPs (10mg/L). Based on the different physiological responses, we speculated that in the pre-illuminated condition, oxidative stress was responsible for the decline in the oxygen evolution rate, while in the post-illuminated condition, the decrease in the Hill reaction activity could be attributed to the blocking of electron transfer and an insufficient proton supply. Our findings demonstrate that environmental factors regulate the physiological responses of plants to AgNPs through distinct mechanisms. PMID:27130969

  8. Computational classification of different wild-type zebrafish strains based on their variation in light-induced locomotor response.

    PubMed

    Gao, Yuan; Zhang, Gaonan; Jelfs, Beth; Carmer, Robert; Venkatraman, Prahatha; Ghadami, Mohammad; Brown, Skye A; Pang, Chi Pui; Leung, Yuk Fai; Chan, Rosa H M; Zhang, Mingzhi

    2016-02-01

    Zebrafish larvae display a rapid and characteristic swimming behaviour after abrupt light onset or offset. This light-induced locomotor response (LLR) has been widely used for behavioural research and drug screening. However, the locomotor responses have long been shown to be different between different wild-type (WT) strains. Thus, it is critical to define the differences in the WT LLR to facilitate accurate interpretation of behavioural data. In this investigation, we used support vector machine (SVM) models to classify LLR data collected from three WT strains: AB, TL and TLAB (a hybrid of AB and TL), during early embryogenesis, from 3 to 9 days post-fertilisation (dpf). We analysed both the complete dataset and a subset of the data during the first 30after light change. This initial period of activity is substantially driven by vision, and is also known as the visual motor response (VMR). The analyses have resulted in three major conclusions: First, the LLR is different between the three WT strains, and at different developmental stages. Second, the distinguishable information in the VMR is comparable to, if not better than, the full dataset for classification purposes. Third, the distinguishable information of WT strains in the light-onset response differs from that in the light-offset response. While the classification accuracies were higher for the light-offset than light-onset response when using the complete LLR dataset, a reverse trend was observed when using a shorter VMR dataset. Together, our results indicate that one should use caution when extrapolating interpretations of LLR/VMR obtained from one WT strain to another. PMID:26688204

  9. CYCLIN H;1 regulates drought stress responses and blue light-induced stomatal opening by inhibiting reactive oxygen species accumulation in Arabidopsis.

    PubMed

    Zhou, Xiao Feng; Jin, Yin Hua; Yoo, Chan Yul; Lin, Xiao-Li; Kim, Woe-Yeon; Yun, Dae-Jin; Bressan, Ray A; Hasegawa, Paul M; Jin, Jing Bo

    2013-06-01

    Arabidopsis (Arabidopsis thaliana) CYCLIN-DEPENDENT KINASE Ds (CDKDs) phosphorylate the C-terminal domain of the largest subunit of RNA polymerase II. Arabidopsis CYCLIN H;1 (CYCH;1) interacts with and activates CDKDs; however, the physiological function of CYCH;1 has not been determined. Here, we report that CYCH;1, which is localized to the nucleus, positively regulates blue light-induced stomatal opening. Reduced-function cych;1 RNA interference (cych;1 RNAi) plants exhibited a drought tolerance phenotype. CYCH;1 is predominantly expressed in guard cells, and its expression was substantially down-regulated by dehydration. Transpiration of intact leaves was reduced in cych;1 RNAi plants compared with the wild-type control in light but not in darkness. CYCH;1 down-regulation impaired blue light-induced stomatal opening but did not affect guard cell development or abscisic acid-mediated stomatal closure. Microarray and real-time polymerase chain reaction analyses indicated that CYCH;1 did not regulate the expression of abscisic acid-responsive genes or light-induced stomatal opening signaling determinants, such as MYB60, MYB61, Hypersensitive to red and blue1, and Protein phosphatase7. CYCH;1 down-regulation induced the expression of redox homeostasis genes, such as LIPOXYGENASE3 (LOX3), LOX4, ARABIDOPSIS GLUTATHIONE PEROXIDASE 7 (ATGPX7), EARLY LIGHT-INDUCIBLE PROTEIN1 (ELIP1), and ELIP2, and increased hydrogen peroxide production in guard cells. Furthermore, loss-of-function mutations in CDKD;2 or CDKD;3 did not affect responsiveness to drought stress, suggesting that CYCH;1 regulates the drought stress response in a CDKD-independent manner. We propose that CYCH;1 regulates blue light-mediated stomatal opening by controlling reactive oxygen species homeostasis. PMID:23656895

  10. Role of Ge:As ratio in controlling the light-induced response of a-Ge(x)As(35-x)Se65 thin films.

    PubMed

    Khan, Pritam; Jain, H; Adarsh, K V

    2014-01-01

    In this paper, we present interesting results on the quantification of photodarkening (PD), photobleaching (PB) and transient PD (TPD) in a-Ge(x)As(35-x)Se65 thin films as a function of network rigidity. Composition dependent light-induced responses of these samples indicate that there exist two parallel competing mechanisms of instantaneous PD arising from the As part of the network, and PB arising from the Ge part of the network. Raman spectra of the as-prepared and illuminated samples provide first direct evidence of the light-induced structural changes: an increase in AsSe3/2 pyramidal and GeSe4/2 corner-sharing tetrahedra units together with new Ge-O bond formation and decrease in energetically unstable edge sharing GeSe4/2 tetrahedra. Importantly, for a fixed Se concentration, Ge:As ratio plays the critical role in controlling the net light-induced response rather than the much believed rigidity of the glassy network. PMID:24504158

  11. Role of Ge:As ratio in controlling the light-induced response of a-GexAs35-xSe65 thin films

    NASA Astrophysics Data System (ADS)

    Khan, Pritam; Jain, H.; Adarsh, K. V.

    2014-02-01

    In this paper, we present interesting results on the quantification of photodarkening (PD), photobleaching (PB) and transient PD (TPD) in a-GexAs35-xSe65 thin films as a function of network rigidity. Composition dependent light-induced responses of these samples indicate that there exist two parallel competing mechanisms of instantaneous PD arising from the As part of the network, and PB arising from the Ge part of the network. Raman spectra of the as-prepared and illuminated samples provide first direct evidence of the light-induced structural changes: an increase in AsSe3/2 pyramidal and GeSe4/2 corner-sharing tetrahedra units together with new Ge-O bond formation and decrease in energetically unstable edge sharing GeSe4/2 tetrahedra. Importantly, for a fixed Se concentration, Ge:As ratio plays the critical role in controlling the net light-induced response rather than the much believed rigidity of the glassy network.

  12. Visible-light-induced synthesis of pH-responsive composite hydrogels for controlled delivery of the anticonvulsant drug pregabalin.

    PubMed

    Cevik, Ozlem; Gidon, Dogan; Kizilel, Seda

    2015-01-01

    We report here a novel method for the synthesis of a pH-responsive composite using visible light. Formation of the pH-responsive layer is based on poly(methacrylic acid-g-ethylene glycol) as the macromer, eosin Y as the photoinitiator and triethanolamine as the co-initiator. The hydrogel was functionalized with hydrophobic domains through incorporation of crosslinked styrene-butadiene-styrene (SBS) copolymer into the pH-responsive prepolymer. Swelling ratios were decreased with the addition of SBS, and resulted in high hydrogel crosslink density. The composite allowed for controlled release of an anticonvulsant model drug, pregabalin, under neutral pH condition and the release was analyzed to describe the mode of transport through the network. In vitro human fibroblast survival assay and in vivo rabbit implantation experiments demonstrated that this hybrid network is not toxic and has desirable biocompatibility properties. This is the first report about the synthesis of a pH-responsive network incorporating crosslinked SBS synthesized under visible light. The approach for multifunctional membranes could allow the incorporation of molecules with specific functionalities so that sequential molecule delivery in response to specific stimuli could be achieved. PMID:25242648

  13. Arabidopsis FHY3 and FAR1 Regulate Light-Induced myo-Inositol Biosynthesis and Oxidative Stress Responses by Transcriptional Activation of MIPS1.

    PubMed

    Ma, Lin; Tian, Tian; Lin, Rongcheng; Deng, Xing-Wang; Wang, Haiyang; Li, Gang

    2016-04-01

    myo-Inositol-1-phosphate synthase (MIPS) catalyzes the limiting step of inositol biosynthesis and has crucial roles in plant growth and development. In response to stress, the transcription of MIPS1 is induced and the biosynthesis of inositol or inositol derivatives is promoted by unknown mechanisms. Here, we found that the light signaling protein FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1) regulate light-induced inositol biosynthesis and oxidative stress responses by activating the transcription of MIPS1. Disruption of FHY3 and FAR1 caused light-induced cell death after dark-light transition, precocious leaf senescence, and increased sensitivity to oxidative stress. Reduction of salicylic acid (SA) accumulation by overexpression of SALICYLIC ACID 3-HYDROXYLASE largely suppressed the cell death phenotype of fhy3 far1 mutant plants, suggesting that FHY3- and FAR1-mediated cell death is dependent on SA. Furthermore, comparative analysis of chromatin immunoprecipitation sequencing and microarray results revealed that FHY3 and FAR1 directly target both MIPS1 and MIPS2. The fhy3 far1 mutant plants showed severely decreased MIPS1/2 transcript levels and reduced inositol levels. Conversely, constitutive expression of MIPS1 partially rescued the inositol contents, caused reduced transcript levels of SA-biosynthesis genes, and prevented oxidative stress in fhy3 far1. Taken together, our results indicate that the light signaling proteins FHY3 and FAR1 directly bind the promoter of MIPS1 to activate its expression and thereby promote inositol biosynthesis to prevent light-induced oxidative stress and SA-dependent cell death. PMID:26714049

  14. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

    ... disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, or ... tract infection) and then a powerful and harmful response by your body’s own immune system . “With sepsis, ...

  15. Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool.

    PubMed

    Shah, Ishan G; Stagner, William C

    2016-08-01

    The effect of percent relative humidity (16-84% RH), moisture content (4.2-6.5% w/w MC), and compression force (4.9-44.1 kN CF) on the light-induced fluorescence (LIF) response of 10% w/w active pharmaceutical ingredient (API) compacts is reported. The fluorescent response was evaluated using two separate central composite designs of experiments. The effect of % RH and CF on the LIF signal was highly significant with an adjusted R (2)  = 0.9436 and p < 0.0001. Percent relative humidity (p = 0.0022), CF (p < 0.0001), and % RH(2) (p = 0.0237) were statistically significant factors affecting the LIF response. The effects of MC and CF on LIF response were also statistically significant with a p value <0.0001 and adjusted R (2) value of 0.9874. The LIF response was highly impacted by MC (p < 0.0001), CF (p < 0.0001), and MC(2) (p = 0022). At 10% w/w API, increased % RH, MC, and CF led to a nonlinear decrease in LIF response. The derived quadratic model equations explained more than 94% of the data. Awareness of these effects on LIF response is critical when implementing LIF as a process analytical tool. PMID:27435199

  16. Phytochrome B-mediated activation of lipoxygenase modulates an excess red light-induced defence response in Arabidopsis

    PubMed Central

    Zhao, Yuanyuan; Zhou, Jun; Xing, Da

    2014-01-01

    Lipoxygenase (LOX), a non-haem-iron-containing dioxygenase, is activated under various biotic or abiotic stresses to trigger a series resistance response, but the molecular mechanism of LOX activation remains unclear. This work investigated the activation of LOX during the plant defence response induced by excess red light (RL). In conditions of RL-induced defence, Arabidopsis LOX activity and transcription levels of LOX2, LOX3, and LOX4 were both upregulated. Under RL, phytochrome B promoted the degradation of phytochrome-interacting factor 3 (PIF3), a factor that inhibited the expression levels of LOXs, and thus the transcription levels of LOX2, LOX3, and LOX4 were increased. Upon pathogen infection, the activity of mitogen-activated protein kinase 3 (MPK3) and MPK6 was increased in plants pre-treated with RL. Moreover, experiments with the inhibitor PD98059 and mutants mpk3 and mpk6-2 demonstrated that MPK3 and MPK6 were both responsible for LOX activation. Further results showed that, in response to RL, an increase in cytoplasmic calcium concentration and upregulation of calmodulin 3 (CaM3) transcript level occurred upstream of MPK3 and MPK6 activation. Collectively, these results suggested that activation of LOX both at the transcript level and in terms of activity modulates the defence response induced by RL, providing a new insight into the mechanistic study of LOX during plant defences. PMID:24916071

  17. Channelrhodopsin-1 Initiates Phototaxis and Photophobic Responses in Chlamydomonas by Immediate Light-Induced Depolarization[W

    PubMed Central

    Berthold, Peter; Tsunoda, Satoshi P.; Ernst, Oliver P.; Mages, Wolfgang; Gradmann, Dietrich; Hegemann, Peter

    2008-01-01

    Channelrhodopsins (CHR1 and CHR2) are light-gated ion channels acting as sensory photoreceptors in Chlamydomonas reinhardtii. In neuroscience, they are used to trigger action potentials by light in neuronal cells, tissues, or living animals. Here, we demonstrate that Chlamydomonas cells with low CHR2 content exhibit photophobic and phototactic responses that strictly depend on the availability of CHR1. Since CHR1 was described as a H+-channel, the ion specificity of CHR1 was reinvestigated in Xenopus laevis oocytes. Our experiments show that, in addition to H+, CHR1 also conducts Na+, K+, and Ca2+. The kinetic selectivity analysis demonstrates that H+ selectivity is not due to specific translocation but due to selective ion binding. Purified recombinant CHR1 consists of two isoforms with different absorption maxima, CHR1505 and CHR1463, that are in pH-dependent equilibrium. Thus, CHR1 is a photochromic and protochromic sensory photoreceptor that functions as a light-activated cation channel mediating phototactic and photophobic responses via depolarizing currents in a wide range of ionic conditions. PMID:18552201

  18. UV-B light induces an adaptive response to UV-C exposure via photoreactivation activity in Euglena gracilis.

    PubMed

    Takahashi, Akihisa; Shibata, Naoaki; Nishikawa, Shoko; Ohnishi, Ken; Ishioka, Noriaki; Ohnishi, Takeo

    2006-05-01

    Phytoplankton such as Euglena are constantly exposed to solar light which is used for photosynthesis. Although the solar ultraviolet (UV) induces DNA damage such as cyclobutane-pyrimidine dimers (CPDs), many kinds of living organisms can repair CPDs by photoreactivation (PR) utilizing the near-UV/blue light component in sunlight. Euglena cells are known to possess such PR activity. In the present paper, the formation of CPDs induced by UV-C exposure and the photoreactivation PR repair of these CPDs by UV-A are demonstrated. To clarify the adaptive responses prior UV-B irradiation on PR activity, cells were cultured in the dark or under UV-B light. When the cells were cultured in the dark for 3 d prior to UV-C exposure, PR activity decreased. When the cells were cultured under UV-B light, however, PR activity increased. These results suggest that exposing the cells to UV-B prior to exposure to UV-C induced an adaptive response towards DNA damage caused by UV-C exposure, and this UV-C induced damage was repaired through PR activity. PMID:16685323

  19. Testicular Nuclear Receptor 4 (TR4) Regulates UV Light-induced Responses via Cockayne Syndrome B Protein-mediated Transcription-coupled DNA Repair*

    PubMed Central

    Liu, Su; Yan, Shian-Jang; Lee, Yi-Fen; Liu, Ning-Chun; Ting, Huei-Ju; Li, Gonghui; Wu, Qiao; Chen, Lu-Min; Chang, Chawnshang

    2011-01-01

    UV irradiation is one of the major external insults to cells and can cause skin aging and cancer. In response to UV light-induced DNA damage, the nucleotide excision repair (NER) pathways are activated to remove DNA lesions. We report here that testicular nuclear receptor 4 (TR4), a member of the nuclear receptor family, modulates DNA repair specifically through the transcription-coupled (TC) NER pathway but not the global genomic NER pathway. The level of Cockayne syndrome B protein (CSB), a member of the TC-NER pathway, is 10-fold reduced in TR4-deficient mouse tissues, and TR4 directly regulates CSB at the transcriptional level. Moreover, restored CSB expression rescues UV hypersensitivity of TR4-deficient cells. Together, these results indicate that TR4 modulates UV sensitivity by promoting the TC-NER DNA repair pathway through transcriptional regulation of CSB. These results may lead to the development of new treatments for UV light-sensitive syndromes, skin cancer, and aging. PMID:21918225

  20. The HT1 protein kinase is essential for red light-induced stomatal opening and genetically interacts with OST1 in red light and CO2 -induced stomatal movement responses.

    PubMed

    Matrosova, Anastasia; Bogireddi, Hanumakumar; Mateo-Peñas, Alfonso; Hashimoto-Sugimoto, Mimi; Iba, Koh; Schroeder, Julian I; Israelsson-Nordström, Maria

    2015-12-01

    The question of whether red light-induced stomatal opening is mediated by a photosynthesis-derived reduction in intercellular [CO2 ] (Ci ) remains controversial and genetic analyses are needed. The Arabidopsis thaliana protein kinase HIGH TEMPERATURE 1 (HT1) is a negative regulator of [CO2 ]-induced stomatal closing and ht1-2 mutant plants do not show stomatal opening to low [CO2 ]. The protein kinase mutant ost1-3 exhibits slowed stomatal responses to CO2 . The functions of HT1 and OPEN STOMATA 1 (OST1) to changes in red, blue light or [CO2 ] were analyzed. For comparison we assayed recessive ca1ca4 carbonic anhydrase double mutant plants, based on their slowed stomatal response to CO2 . Here, we report a strong impairment in ht1 in red light-induced stomatal opening whereas blue light was able to induce stomatal opening. The effects on photosynthetic performance in ht1 were restored when stomatal limitation of CO2 uptake, by control of [Ci ], was eliminated. HT1 was found to interact genetically with OST1 both during red light- and low [CO2 ]-induced stomatal opening. Analyses of ca1ca4 plants suggest that more than a low [Ci ]-dependent pathway may function in red light-induced stomatal opening. These results demonstrate that HT1 is essential for red light-induced stomatal opening and interacts genetically with OST1 during stomatal responses to red light and altered [CO2 ]. PMID:26192339

  1. Exclusion of the Unfolded Protein Response in Light-Induced Retinal Degeneration in the Canine T4R RHO Model of Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Marsili, Stefania; Genini, Sem; Sudharsan, Raghavi; Gingrich, Jeremy; Aguirre, Gustavo D.; Beltran, William A.

    2015-01-01

    Purpose To examine the occurrence of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) following acute light damage in the naturally-occurring canine model of RHO-adRP (T4R RHO dog). Methods The left eyes of T4R RHO dogs were briefly light-exposed and retinas collected 3, 6 and 24 hours later. The contra-lateral eyes were shielded and used as controls. To evaluate the time course of cell death, histology and TUNEL assays were performed. Electron microscopy was used to examine ultrastructural alterations in photoreceptors at 15 min, 1 hour, and 6 hours after light exposure. Gene expression of markers of ER stress and UPR were assessed by RT-PCR, qRT-PCR and western blot at the 6 hour time-point. Calpain and caspase-3 activation were assessed at 1, 3 and 6 hours after exposure. Results A brief exposure to clinically-relevant levels of white light causes within minutes acute disruption of the rod outer segment disc membranes, followed by prominent ultrastructural alterations in the inner segments and the initiation of cell death by 6 hours. Activation of the PERK and IRE1 pathways, and downstream targets (BIP, CHOP) of the UPR was not observed. However increased transcription of caspase-12 and hsp70 occurred, as well as calpain activation, but not that of caspase-3. Conclusion The UPR is not activated in the early phase of light-induced photoreceptor cell death in the T4R RHO model. Instead, disruption in rods of disc and plasma membranes within minutes after light exposure followed by increase in calpain activity and caspase-12 expression suggests a different mechanism of degeneration. PMID:25695253

  2. Photoreceptor IRBP prevents light induced injury.

    PubMed

    Sun, Zhongcui; Zhang, Meng; Liu, Wei; Tian, Jie; Xu, Gezhi

    2016-01-01

    Interphotoreceptor retinoid-binding protein (IRBP) is a classic inducer of experimental autoimmune uveoretinitis (EAU). Although IRBP causes neuronal loss in susceptible animals, resistant animals such as Sprague-Dawley (SPD) rats can benefit from the evoked protective autoimmune responses. The aim of the present study was to analyze the neuroprotective effects of IRBP against light-induced photoreceptor degeneration. We immunized 75 male SPD rats with IRBP and the rats were then exposed to blue light for 24 hours (IRBP group). Seventy five rats were included in the control group. We found that the number of apoptotic cells in the outer nuclear layer (ONL) peaked on 1 day after light exposure, and the ONL thickness decreased significantly on day 3. OX42-positive cells appeared in the ONL immediately after light exposure, and their number peaked on day 3, and changed from resting ramified cells to activated amoeboid cells. Compared with the control group (n=75), the IRBP group showed less apoptotic cells, a thicker ONL, and reduced expression of tumor necrosis factor-alpha. These outcomes indicate the IRPB might protect retinal photoreceptors against light-induced injury. PMID:27100484

  3. SURVIVAL AND IMMUNE RESPONSE OF COHO SALMON EXPOSED TO COPPER

    EPA Science Inventory

    Vaccination with Vibrio anguillarum by oral administration during copper exposure and intraperitoneal injection prior to copper exposure was employed to investigate the effects of copper upon survival and the immune response of juvenile coho salmon (Oncorhynchus kisutch). Followi...

  4. The Responses of Arabidopsis Early Light-Induced Protein2 to Ultraviolet B, High Light, and Cold Stress Are Regulated by a Transcriptional Regulatory Unit Composed of Two Elements1[OPEN

    PubMed Central

    Hayami, Natsuki; Sakai, Yusaku; Kimura, Mitsuhiro; Saito, Tatsunori; Tokizawa, Mutsutomo; Iuchi, Satoshi; Kurihara, Yukio; Matsui, Minami; Nomoto, Mika; Tada, Yasuomi; Yamamoto, Yoshiharu Y.

    2015-01-01

    The Arabidopsis (Arabidopsis thaliana) Early Light-Induced Protein (ELIP) is thought to act as a photoprotectant, reducing the damaging effects of high light (HL). Expression of ELIP2 is activated by multiple environmental stresses related to photoinhibition. We have identified putative regulatory elements in an ELIP2 promoter using an octamer-based frequency comparison method, analyzed the role of these elements using synthetic promoters, and revealed a key transcriptional regulatory unit for ultraviolet B (UV-B) radiation, HL, and cold stress responses. The unit is composed of two elements, designated as Elements A (TACACACC) and B (GGCCACGCCA), and shows functionality only when paired. Our genome-wide correlation analysis between possession of these elements in the promoter region and expression profiles in response to UV-B, HL, and cold suggests that Element B receives and integrates these multiple stress signals. In vitro protein-DNA binding assays revealed that LONG HYPOCOTYL5 (HY5), a basic domain-Leucine zipper transcription factor, directly binds to Element B. In addition, mutant analysis of HY5 showed partial involvement in the UV-B and HL responses but not in the cold stress response. These results suggest that signals for UV-B, HL, and cold stress join at Element B, which recognizes the signals of multiple transcription factors, including HY5. PMID:26175515

  5. The Responses of Arabidopsis Early Light-Induced Protein2 to Ultraviolet B, High Light, and Cold Stress Are Regulated by a Transcriptional Regulatory Unit Composed of Two Elements.

    PubMed

    Hayami, Natsuki; Sakai, Yusaku; Kimura, Mitsuhiro; Saito, Tatsunori; Tokizawa, Mutsutomo; Iuchi, Satoshi; Kurihara, Yukio; Matsui, Minami; Nomoto, Mika; Tada, Yasuomi; Yamamoto, Yoshiharu Y

    2015-09-01

    The Arabidopsis (Arabidopsis thaliana) Early Light-Induced Protein (ELIP) is thought to act as a photoprotectant, reducing the damaging effects of high light (HL). Expression of ELIP2 is activated by multiple environmental stresses related to photoinhibition. We have identified putative regulatory elements in an ELIP2 promoter using an octamer-based frequency comparison method, analyzed the role of these elements using synthetic promoters, and revealed a key transcriptional regulatory unit for ultraviolet B (UV-B) radiation, HL, and cold stress responses. The unit is composed of two elements, designated as Elements A (TACACACC) and B (GGCCACGCCA), and shows functionality only when paired. Our genome-wide correlation analysis between possession of these elements in the promoter region and expression profiles in response to UV-B, HL, and cold suggests that Element B receives and integrates these multiple stress signals. In vitro protein-DNA binding assays revealed that LONG HYPOCOTYL5 (HY5), a basic domain-Leucine zipper transcription factor, directly binds to Element B. In addition, mutant analysis of HY5 showed partial involvement in the UV-B and HL responses but not in the cold stress response. These results suggest that signals for UV-B, HL, and cold stress join at Element B, which recognizes the signals of multiple transcription factors, including HY5. PMID:26175515

  6. Sprayed zinc oxide films: Ultra-violet light-induced reversible surface wettability and platinum-sensitization-assisted improved liquefied petroleum gas response.

    PubMed

    Nakate, Umesh T; Patil, Pramila; Bulakhe, R N; Lokhande, C D; Kale, Sangeeta N; Naushad, Mu; Mane, Rajaram S

    2016-10-15

    We report the rapid (superhydrophobic to superhydrophilic) transition property and improvement in the liquefied petroleum gas (LPG) sensing response of zinc oxide (ZnO) nanorods (NRs) on UV-irradiation and platinum (Pt) surface sensitization, respectively. The morphological evolution of ZnO NRs is evidenced from the field emission scanning electron microscope and atomic force microscope digital images and for the structural elucidation X-ray diffraction pattern is used. Elemental survey mapping is obtained from energy dispersive X-ray analysis spectrum. The optical properties have been studied by UV-Visible and photoluminescence spectroscopy measurements. The rapid (120sec) conversion of superhydrophobic (154°) ZnO NRs film to superhydrophilic (7°) is obtained under UV light illumination and the superhydrophobicity is regained by storing sample in dark. The mechanism for switching wettability behavior of ZnO NRs has thoroughly been discussed. In second phase, Pt-sensitized ZnO NRs film has demonstrated considerable gas sensitivity at 260ppm concentration of LPG. At 623K operating temperature, the maximum LPG response of 58% and the response time of 49sec for 1040ppm LPG concentration of Pt- sensitized ZnO NRs film are obtained. This higher LPG response of Pt-sensitized ZnO NRs film over pristine is primarily due to electronic effect and catalytic effect (spill-over effect) caused by an additional of Pt on ZnO NRs film surface. PMID:27421113

  7. Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase.

    PubMed

    Iyisan, Banu; Janke, Andreas; Reichenbach, Philipp; Eng, Lukas M; Appelhans, Dietmar; Voit, Brigitte

    2016-06-22

    Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane-β-cyclodextrin host-guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young's modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors. PMID

  8. Association of response endpoints with survival outcomes in multiple myeloma

    PubMed Central

    Lonial, S; Anderson, K C

    2014-01-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  9. Association of response endpoints with survival outcomes in multiple myeloma.

    PubMed

    Lonial, S; Anderson, K C

    2014-02-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  10. Autophagy in light-induced retinal damage.

    PubMed

    Chen, Yu; Perusek, Lindsay; Maeda, Akiko

    2016-03-01

    Vision is reliant upon converting photon signals to electrical information which is interpreted by the brain and therefore allowing us to receive information about our surroundings. However, when exposed to excessive light, photoreceptors and other types of cells in the retina can undergo light-induced cell death, termed light-induced retinal damage. In this review, we summarize our current knowledge regarding molecular events in the retina after excessive light exposure and mechanisms of light-induced retinal damage. We also introduce works which investigate potential roles of autophagy, an essential cellular mechanism required for maintaining homeostasis under stress conditions, in the illuminated retina and animal models of light-induced retinal damage. PMID:26325327

  11. Light-induced actuating nanotransducers.

    PubMed

    Ding, Tao; Valev, Ventsislav K; Salmon, Andrew R; Forman, Chris J; Smoukov, Stoyan K; Scherman, Oren A; Frenkel, Daan; Baumberg, Jeremy J

    2016-05-17

    Nanoactuators and nanomachines have long been sought after, but key bottlenecks remain. Forces at submicrometer scales are weak and slow, control is hard to achieve, and power cannot be reliably supplied. Despite the increasing complexity of nanodevices such as DNA origami and molecular machines, rapid mechanical operations are not yet possible. Here, we bind temperature-responsive polymers to charged Au nanoparticles, storing elastic energy that can be rapidly released under light control for repeatable isotropic nanoactuation. Optically heating above a critical temperature [Formula: see text] = 32 °C using plasmonic absorption of an incident laser causes the coatings to expel water and collapse within a microsecond to the nanoscale, millions of times faster than the base polymer. This triggers a controllable number of nanoparticles to tightly bind in clusters. Surprisingly, by cooling below [Formula: see text] their strong van der Waals attraction is overcome as the polymer expands, exerting nanoscale forces of several nN. This large force depends on van der Waals attractions between Au cores being very large in the collapsed polymer state, setting up a tightly compressed polymer spring which can be triggered into the inflated state. Our insights lead toward rational design of diverse colloidal nanomachines. PMID:27140648

  12. Rapid changes in protein phosphorylation associated with light-induced gravity perception in corn roots

    NASA Technical Reports Server (NTRS)

    McFadden, J. J.; Poovaiah, B. W.

    1988-01-01

    The effect of light and calcium depletion on in vivo protein phosphorylation was tested using dark-grown roots of Merit corn. Light caused rapid and specific promotion of phosphorylation of three polypeptides. Pretreatment of roots with ethylene glycol bis N,N,N',N' tetraacetic acid and A23187 prevented light-induced changes in protein phosphorylation. We postulate that these changes in protein phosphorylation are involved in the light-induced gravity response.

  13. Metastable light induced defects in pentacene

    SciTech Connect

    Liguori, R.; Aprano, S.; Rubino, A.

    2014-02-21

    In this study we analyzed one of the environmental factors that could affect organic materials. Pentacene thin film samples were fabricated and the degradation of their electrical characteristics was measured when the devices were exposed to ultraviolet light irradiation. The results have been reported in terms of a trap density model, which provides a description of the dynamics of light induced electrically active defects in an organic semiconductor.

  14. Strain Differences in Light-Induced Retinopathy

    PubMed Central

    Polosa, Anna; Bessaklia, Hyba; Lachapelle, Pierre

    2016-01-01

    The purpose of this study was to better understand the role of ocular pigmentation and genetics in light-induced retinal damage. Adult pigmented [Long Evans (LE) and Brown Norway (BN)] and albino [Sprague Dawley (SD) and Lewis (LW)] rats were exposed to a bright cyclic light for 6 consecutive days and where compared with juvenile animals exposed to the same bright light environment from postnatal age 14 to 28. Flash ERGs and retinal histology were performed at predetermined days (D) post-light exposure. At D1, ERGs were similar in all adult groups with no recordable a-waves and residual b-waves. A transient recovery was noticed at D30 in the LW and LE only [b-wave: 18% and 25% of their original amplitude respectively]. Histology revealed that BN retina was the most damaged, while LE retina was best preserved. SD and LW rats were almost as damaged as BN rats. In contrast, the retina of juvenile BN was almost as resistant to the bright light exposure as that of juvenile LE rats. Our results strongly suggest that, although ocular pigmentation and genetic background are important factors in regulating the severity of light-induced retinal damage, the age of the animal at the onset of light exposure appears to be the most important determining factor. PMID:27355622

  15. Functional analysis of chloroplast early light inducible proteins (ELIPs)

    SciTech Connect

    Wetzel, Carolyn M

    2005-02-22

    The objectives of this project were to characterize gene expression patterns of early light inducible protein (ELIP) genes in Arabidopsis thaliana and in Lycopersicon esculentum, to identify knock mutants of the 2 ELIP genes in Arabidopsis, and to characterize the effects of the knockouts. Expression in Arabidopsis was studied in response to thylakoid electron transport chain (PETC) capacity, where it was found that there is a signal for expression associated with reduction of the PETC. Expression in response to salt was also studied, with different responses of the two gene copies. Knockout lines for ELIP1 and ELIP2 have been identified and are being characterized. In tomato, it was found that the single-copy ELIP gene is highly expressed in ripening fruit during the chloroplast-to-chromoplast transition. Studies of expression in tomato ripening mutants are ongoing.

  16. Transient light-induced intracellular oxidation revealed by redox biosensor

    SciTech Connect

    Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

    2013-10-04

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

  17. Preimplantation Mouse Embryo Selection Guided by Light-Induced Dielectrophoresis

    PubMed Central

    Valley, Justin K.; Swinton, Paul; Boscardin, W. John; Lue, Tom F.; Rinaudo, Paolo F.; Wu, Ming C.; Garcia, Maurice M.

    2010-01-01

    Selection of optimal quality embryos for in vitro fertilization (IVF) transfer is critical to successful live birth outcomes. Currently, embryos are chosen based on subjective assessment of morphologic developmental maturity. A non-invasive means to quantitatively measure an embryo's developmental maturity would reduce the variability introduced by the current standard. We present a method that exploits the scaling electrical properties of pre-transfer embryos to quantitatively discern embryo developmental maturity using light-induced dielectrophoresis (DEP). We show that an embryo's DEP response is highly correlated with its developmental stage. Uniquely, this technique allows one to select, in sequence and under blinded conditions, the most developmentally mature embryos among a mixed cohort of morphologically indistinguishable embryos cultured in optimized and sub-optimal culture media. Following assay, embryos continue to develop normally in vitro. Light-induced dielectrophoresis provides a non-invasive, quantitative, and reproducible means to select embryos for applications including IVF transfer and embryonic stem cell harvest. PMID:20405021

  18. Light-induced effects in dye-doped liquid crystals: role of space charges

    NASA Astrophysics Data System (ADS)

    Simoni, F.; Lucchetti, L.

    2014-10-01

    We report the experimental demonstration that both the extra-ordinarily large nonlinear response and the light-induced permanent reorientation in liquid crystals doped by the azo-dye Methyl-Red originates from the modification of the charge density on the irradiated surface. By recording the sample response by applying dc or ac voltage, it is shown that in the latter case no permanent anchoring is possible. It is also demonstrated the limited role of photo-isomerization that gives a contribution to the nonlinear reorientation process only in the high dose regime. The effects on light-induced tuning of the Freedericksz transition are also reported.

  19. Light-Induced Dielectrophoretic Manipulation of DNA

    PubMed Central

    Hoeb, Marco; Rädler, Joachim O.; Klein, Stefan; Stutzmann, Martin; Brandt, Martin S.

    2007-01-01

    Light-induced dielectrophoretic movement of polystyrene beads and λ-DNA is studied using thin films of amorphous hydrogenated silicon as local photoaddressable electrodes with a diameter of 4 μm. Positive (high-field seeking) dielectrophoretic movement is observed for both types of objects. The absence of strong negative (low-field seeking) dielectrophoresis of DNA at high frequencies is in agreement with the similarity of the dielectric constants of DNA and water, the real part of the dielectric function. The corresponding imaginary part of the dielectric function governed by the conductivity of DNA can be determined from a comparison of the frequency dependence of the dielectrophoretic drift velocity with the Clausius-Mossotti relation. PMID:17483160

  20. Broadband Visible Light Induced NO Formation

    NASA Astrophysics Data System (ADS)

    Lubart, Rachel; Eichler, Maor; Friedmann, Harry; Savion, N.; Breitbart, Haim; Ankri, Rinat

    2009-06-01

    Nitric oxide formation is a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme, and thus absorbs visible light. The purpose of this work was to study broadband visible light induced NO formation in various cells. Cardiac, endothelial, sperm cells and RAW 264.7 macrophages were illuminated with broadband visible light, 40-130 mW/cm2, 2.4-39 J/cm2, and nitric oxide production was quantified by using the Griess reagent. The results showed that visible light illumination increased NO concentration both in sperm and endothelial cells, but not in cardiac cells. Activation of RAW 264.7 macrophages was very small. It thus appears that NO is involved in photobiomodulation, though different light parameters and illumination protocols are needed to induce NO in various cells.

  1. A light-induced microwave oscillator

    NASA Technical Reports Server (NTRS)

    Yao, X. S.; Maleki, L.

    1995-01-01

    We describe a novel oscillator that converts continuous light energy into sta ble and spectrally pure microwave signals. This light-induced microwave oscillator (LIMO) consists of a pump laser and a feedback circuit, including an intensity modulator, an optical fiber delay line, a photodetector, an amplifier, and a filter. We develop a quasilinear theory and obtain expressions for the threshold condition, the amplitude, the frequency, the line width, and the spectral power density of the oscillation. We also present experimental data to compare with the theoretical results. Our findings indicate that the LIMO can generate ultrastable, spectrally pure microwave reference signals up to 75 GHz with a phase noise lower than -140 dBc/Hz at 10 kHz.

  2. Broadband Visible Light Induced NO Formation

    SciTech Connect

    Lubart, Rachel; Eichler, Maor; Friedmann, Harry; Ankri, Rinat; Savion, N.; Breitbart, Haim

    2009-06-19

    Nitric oxide formation is a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme, and thus absorbs visible light. The purpose of this work was to study broadband visible light induced NO formation in various cells. Cardiac, endothelial, sperm cells and RAW 264.7 macrophages were illuminated with broadband visible light, 40-130 mW/cm2, 2.4-39 J/cm2, and nitric oxide production was quantified by using the Griess reagent. The results showed that visible light illumination increased NO concentration both in sperm and endothelial cells, but not in cardiac cells. Activation of RAW 264.7 macrophages was very small. It thus appears that NO is involved in photobiomodulation, though different light parameters and illumination protocols are needed to induce NO in various cells.

  3. Light-induced currents in Xenopus oocytes expressing bovine rhodopsin.

    PubMed Central

    Knox, B E; Khorana, H G; Nasi, E

    1993-01-01

    1. We have investigated the functioning of bovine rod opsin, which is efficiently synthesized from RNA made by in vitro transcription, following injection into Xenopus oocytes. We found that oocytes expressing the gene for opsin exhibit light-dependent ionic currents only after pigment generation by incubation with 11-cis-retinal. These currents are similar to the endogenous muscarinic acetylcholine (ACh) response of oocytes, but their amplitude is substantially smaller. 2. In order to optimize the conditions for obtaining light-induced currents in RNA-injected oocytes, the native ACh response was examined under several conditions. It was found that elevated external calcium markedly enhances the muscarinic response and that these currents have a non-linear dependence on membrane voltage, increasing substantially with depolarization. 3. Using the optimal conditions for evoking the largest ACh responses, (28 mM [Ca2+]o, 0 mV, omission of serum and Hepes from the media), the light-evoked currents obtained in RNA-injected oocytes were remarkably enhanced, and responses to multiple light stimuli could be obtained. 4. The light response appeared to desensitize, even after long periods of recovery and pigment regeneration. By contrast, the ACh responses continued to appear normal. These results suggest that desensitization of photoresponses expressed in Xenopus oocytes involve changes at early stages of the pathway, resulting in a reduced ability of rhodopsin to couple to the endogenous signalling system. Images Fig. 3 PMID:7692039

  4. EDITORIAL Light-induced material organization Light-induced material organization

    NASA Astrophysics Data System (ADS)

    Vainos, Nikos; Rode, Andrei V.

    2010-12-01

    Light-induced material organization extends over a broad area of research, from photon momentum transfer to atoms, molecules and particles, serving the basis for optical trapping, and expands into the laser-induced changes of material properties through photopolymerization, photodarkening, and materials ablation. Relevant phenomena are observed over many orders of magnitude of light intensity, from a few kW cm-2 for the optical trapping of living cells to 1014 W cm-2 encountered in femtosecond laser micromachining and micro-explosion. Relevant interactions reveal a rich palette of novel phenomena in the solid state, from subtle excitations and material organization to phase transformations, non-equilibrium and transient states. The laser-induced material modifications relate to changes in the crystal structure and the molecular bonding, phase transitions in liquid state, ablation and plasma production associated with extreme pressure and temperature conditions towards entirely new states of matter. The underlying physical mechanisms form the foundations for micro-engineering photonic and other functional devices and lead the way to relevant applications. At the same time, they hold the potential for creating non-equilibrium material states and a range of fundamentally new products not available by other means. The fundamental understanding of both materials nature and functional behaviour will ultimately yield novel devices and improved performance in several fields. The far reaching goals of these studies relate to the development of new methods and technologies for micro- and nano-fabrication, not only offering a significant reduction of cost, but also expanding the fabrication capabilities into unexplored areas of biophotonics and nanotechnology. This special issue of Journal of Optics presents some very recent and exciting advances in the field of materials manipulation by laser beams, aiming to underline its current trends. In optical trapping research we

  5. Light-induced fluorescence for pulpal diagnosis

    NASA Astrophysics Data System (ADS)

    Ebihara, Arata; Liaw, Lih-Huei L.; Krasieva, Tatiana B.; Wilder-Smith, Petra B. B.

    2001-04-01

    A direct non-histological means of pulpal diagnosis remains elusive to clinical practice. Clinical vitality testing remains limited to electric, thermal criteria, or laser Doppler flowmetry. The goal of these investigations was to determine the feasibility of using light-induced fluorescence as a non-invasive modality for pulpal evaluation. Such a capability would, for example, permit expanded use of pulpotomy/pulpectomy techniques. Clinically healthy and diseased human extirpated pulpal tissues were used in this study. After excision, they were rapidly frozen and standard cryosections prepared. Measurement of tissue excitation/emission characteristics was performed using spectrographic analysis. A low-light level fluorescence microscopy system was then used to image autofluorescence localization and intensity at optimal excitation/detection parameters. Excitation/detection parameters used in this study included 405/605, 405/635, 405/670, 440/550, and 440/635. Autofluorescence intensities in healthy tissues were significantly stronger than those in diseased tissues at optimal parameters. It is postulated that autofluorescence characteristics are related to pathology- related structural changes in the pulp. This work provides the basis for further investigation into the relation between autofluorescence, histology and clinical symptoms.

  6. Light-induced atomic desorption: recent developments

    NASA Astrophysics Data System (ADS)

    Mariotti, E.; Atutov, S. N.; Biancalana, Valerio; Bocci, S.; Burchianti, A.; Marinelli, C.; Nasyrov, K. A.; Pieragnoli, B.; Moi, L.

    2001-04-01

    Light induced atomic desorption (LIAD) is an impressive manifestation of a new class of phenomena involving alkali atoms, dielectric films and light. LIAD consists of a huge emission of alkali atoms (experimentally proved for sodium, potassium, rubidium and cesium) from siloxane films when illuminated by laser or ordinary light. Most of the experiments have been performed in glass cells suitably coated by a thin film (of the order of 10 micrometer) either of poly - (dimethylsiloxane) (PDMS), a polymer, or of octamethylcyclotetrasiloxane (OCT), a crown molecule. LIAD is a combination of two processes: direct photo-desorption from the surface and diffusion within the siloxane layer. The photo-desorbed atoms are replaced by fresh atoms diffusing to the surface. Moreover, from the experimental data it comes out that the desorbing light increases atomic diffusion and hence the diffusion coefficient. To our knowledge this is the first time that such an effect is clearly observed, measured and discussed: LIAD represents a new class of photo-effects characterized by two simultaneous phenomena due to the light: surface desorption and fastened bulk diffusion.

  7. An Analysis of Light-Induced Retroactive Inhibition in Pigeon Short-Term Memory

    ERIC Educational Resources Information Center

    Roberts, William A.; Grant, Douglas S.

    1978-01-01

    Grant and Roberts found that houselight presented throughout the delay period on a delayed matching-to-sample task caused pigeons to demonstrate a much lower level of accuracy than was found when the delay was spent in darkness. A series of experiments was carried out to examine possible mechanisms responsible for this light-induced retroactive…

  8. Light-induced changes of sensitivity in Limulus ventral photoreceptors

    PubMed Central

    1975-01-01

    The responses of Limulus ventral photoreceptors to brief test flashes and to longer adapting lights were measured under voltage clamp conditions. When the cell was dark adapted, there was a range of energy of the test flashes over which the peak amplitude of the responses (light-induced currents) was directly proportional to the flash energy. This was also true when test flashes were superposed on adapting stimuli but the proportionality constant (termed peak currently/photon) was reduced. The peak current/photon was attenuated more by brighter adapting stimuli than by less bright adapting stimuli. The peak current/photon is a measure of the sensitivity of the conductance- increase mechanism underlying the light response of the photo-receptor. The response elicited by an adapting stimulus had a large initial transient which declined to a smaller plateau. The peak current/photon decreased sharply during the declining phase of the transient and was relatively stable during the plateau. This indicates that the onset of light adaptation is delayed with respect to the onset of the response to the adapting stimulus. If the adaptational state just before the onset of each of a series of adapting stimuli was constant, the amplitude of the transient was a nearly linear function of intensity. When the total intensity was rapidly doubled (or halved) during a plateau response, the total current approximately doubled (or halved). We argue that the transition from transient to plateau, light-elicited changes of threshold, and the nonlinear function relating the plateau response to stimulus intensity all reflect changes of the responsiveness of the conductance-increase mechanism. PMID:1181378

  9. The regulatory mechanism underlying light-inducible production of carotenoids in nonphototrophic bacteria.

    PubMed

    Takano, Hideaki

    2016-07-01

    Light is a ubiquitous environmental factor serving as an energy source and external stimulus. Here, I review the conserved molecular mechanism of light-inducible production of carotenoids in three nonphototrophic bacteria: Streptomyces coelicolor A3(2), Thermus thermophilus HB27, and Bacillus megaterium QM B1551. A MerR family transcriptional regulator, LitR, commonly plays a central role in their light-inducible carotenoid production. Genetic and biochemical studies on LitR proteins revealed a conserved function: LitR in complex with adenosyl B12 (AdoB12) has a light-sensitive DNA-binding activity and thus suppresses the expression of the Crt biosynthesis gene cluster. The in vitro DNA-binding and transcription assays showed that the LitR-AdoB12 complex serves as a repressor allowing transcription initiation by RNA polymerase in response to illumination. The existence of novel light-inducible genes and the unique role of the megaplasmid were revealed by the transcriptomic analysis of T. thermophilus. The findings suggest that LitR is a general regulator responsible for the light-inducible carotenoid production in the phylogenetically divergent nonphototrophic bacteria, and that LitR performs diverse physiological functions in bacteria. PMID:26967471

  10. Predicting response and survival in chemotherapy-treated triple-negative breast cancer

    PubMed Central

    Prat, A; Lluch, A; Albanell, J; Barry, W T; Fan, C; Chacón, J I; Parker, J S; Calvo, L; Plazaola, A; Arcusa, A; Seguí-Palmer, M A; Burgues, O; Ribelles, N; Rodriguez-Lescure, A; Guerrero, A; Ruiz-Borrego, M; Munarriz, B; López, J A; Adamo, B; Cheang, M C U; Li, Y; Hu, Z; Gulley, M L; Vidal, M J; Pitcher, B N; Liu, M C; Citron, M L; Ellis, M J; Mardis, E; Vickery, T; Hudis, C A; Winer, E P; Carey, L A; Caballero, R; Carrasco, E; Martín, M; Perou, C M; Alba, E

    2014-01-01

    Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). Methods: Gene expression and clinical–pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55–81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not. PMID:25101563

  11. Radiographic Response to Locoregional Therapy in Hepatocellular Carcinoma Predicts Patient Survival Times

    PubMed Central

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-01-01

    Background & Aims It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs; chemoembolization and radioembolization). Methods Patients received LRTs over a 9-year period (n=463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh≤B7 were analyzed. Response (based on European Association for Study of the Liver [EASL] or World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Results Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P=0.002 and 0.0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P=0.0463 and 0.707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P=<0.0001 and 0.004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P=0.0132 and 0.010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P<0.0001; P=0.596 with WHO criteria). In the subanalysis, responders lived longer than patients with SD or PD. Conclusion Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. PMID:21664356

  12. Light-induced hopping conductivity in a transparent oxide

    NASA Astrophysics Data System (ADS)

    Medvedeva, J. E.; Freeman, A. J.; Bertoni, M. I.; Mason, T. O.

    2004-03-01

    Recently, Hayashi et al (K. Hayashi et al), Nature 419, 462 (2002) found a way to convert a transparent oxide into a persistent conductor using UV light. The simplicity of the insulator-conductor conversion (hydrogen annealing followed by UV irradiation) and the resulting drastic change in conductivity (by 10 orders of magnitude) makes this material an extremely attractive starting point for optoelectronic applications. Despite careful experimental studies, no definitive understanding has been reached on the underlying mechanism responsible for this new dramatic effect. Here we demonstrate that ab-initio calculations provide a detailed explanation of the experimental findings and reveal the origin of the light-induced conductivity. We (i) show that the charge transport, associated with photo-excitation of an electron from hydrogen, occurs by electron hopping, (ii) determine the exact paths for the carrier migration and (iii) derive the temperature behavior of the hopping conductivity. We predict the strong dependence of the transport on the particular hopping centers and their spatial arrangement which is confirmed by our measurements, and investigate the possibility of varying the conductivity by proper doping.

  13. A light-induced shortcut in the planktonic microbial loop.

    PubMed

    Ptacnik, Robert; Gomes, Ana; Royer, Sarah-Jeanne; Berger, Stella A; Calbet, Albert; Nejstgaard, Jens C; Gasol, Josep M; Isari, Stamatina; Moorthi, Stefanie D; Ptacnikova, Radka; Striebel, Maren; Sazhin, Andrey F; Tsagaraki, Tatiana M; Zervoudaki, Soultana; Altoja, Kristi; Dimitriou, Panagiotis D; Laas, Peeter; Gazihan, Ayse; Martínez, Rodrigo A; Schabhüttl, Stefanie; Santi, Ioulia; Sousoni, Despoina; Pitta, Paraskevi

    2016-01-01

    Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10-fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light. PMID:27404551

  14. A light-induced shortcut in the planktonic microbial loop

    PubMed Central

    Ptacnik, Robert; Gomes, Ana; Royer, Sarah-Jeanne; Berger, Stella A.; Calbet, Albert; Nejstgaard, Jens C.; Gasol, Josep M.; Isari, Stamatina; Moorthi, Stefanie D.; Ptacnikova, Radka; Striebel, Maren; Sazhin, Andrey F.; Tsagaraki, Tatiana M.; Zervoudaki, Soultana; Altoja, Kristi; Dimitriou, Panagiotis D.; Laas, Peeter; Gazihan, Ayse; Martínez, Rodrigo A.; Schabhüttl, Stefanie; Santi, Ioulia; Sousoni, Despoina; Pitta, Paraskevi

    2016-01-01

    Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10-fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light. PMID:27404551

  15. A possible mechanism for visible-light-induced skin rejuvenation

    NASA Astrophysics Data System (ADS)

    Longo, Leonardo; Lubart, Rachel; Friedman, Harry; Lavie, R.

    2004-09-01

    In recent years there has been intensive research in the field of non-ablative skin rejuvenation. This comes as a response to the desire for a simple method of treating rhytids caused by aging, UV exposure and acne scars. In numerous studies intense visible light pulsed systems (20-30J/cm2) are used. The mechanism of action was supposed to be a selective heat induced denaturalization of dermal collagen that leads to subsequent reactive synthesis. In this study we suggest a different mechanism for photorejuvenation based on light induced Reactive Oxygen Species (ROS) formation. We irradiated collagen in-vitro with a broad band of visible light, 400-800 nm, 12-22J/cm2, and used the spin trapping coupled with electron paramagnetic resonance (EPR) spectroscopy to detect ROS. In vivo, we used dose 30 J in average (35 for acnis scars, 25 for wrinkles and redness). Irradiated collagen results in hydroxyl and methyl radicals formation. We propose, as a new concept, that visible light at the intensity used for skin rejuvenation, 20-30J/cm2, produces high amounts of ROS which destroy old collagen fibers encouraging the formation of new ones. On the other hand at inner depths of the skin, where the light intensity is much weaker, low amounts of ROS are formed which are well known to stimulate fibroblast proliferation.

  16. Ab initio investigation of light-induced relativistic spin-flip effects in magneto-optics

    NASA Astrophysics Data System (ADS)

    Mondal, Ritwik; Berritta, Marco; Carva, Karel; Oppeneer, Peter M.

    2015-05-01

    Excitation of a metallic ferromagnet such as Ni with an intensive femtosecond laser pulse causes an ultrafast demagnetization within approximately 300 fs. It was proposed that the ultrafast demagnetization measured in femtosecond magneto-optical experiments could be due to relativistic light-induced processes. We perform an ab initio investigation of the influence of relativistic effects on the magneto-optical response of Ni. To this end, first, we develop a response theory formulation of the additional appearing ultrarelativistic terms in the Foldy-Wouthuysen transformed Dirac Hamiltonian due to the electromagnetic field, and second, we compute the influence of relativistic light-induced spin-flip transitions on the magneto-optics. Our ab initio calculations of relativistic spin-flip optical excitations predict that these can give only a very small contribution (≤0.1 %) to the laser-induced magnetization change in Ni.

  17. Light-induced cytotoxicity of a photochromic spiropyran.

    PubMed

    Nilsson, Jesper R; Li, Shiming; Önfelt, Björn; Andréasson, Joakim

    2011-10-21

    In this work we present a novel water soluble spiropyran photoswitch that can be photonically activated inside live cells from a form that has no significant effect on the cellular survival to a form that induces a dramatic toxic response. PMID:21909522

  18. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    SciTech Connect

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-05-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.

  19. Light-Inducible Gene Regulation with Engineered Zinc Finger Proteins

    PubMed Central

    Polstein, Lauren R.; Gersbach, Charles A.

    2014-01-01

    The coupling of light-inducible protein-protein interactions with gene regulation systems has enabled the control of gene expression with light. In particular, heterodimer protein pairs from plants can be used to engineer a gene regulation system in mammalian cells that is reversible, repeatable, tunable, controllable in a spatiotemporal manner, and targetable to any DNA sequence. This system, Light-Inducible Transcription using Engineered Zinc finger proteins (LITEZ), is based on the blue light-induced interaction of GIGANTEA and the LOV domain of FKF1 that drives the localization of a transcriptional activator to the DNA-binding site of a highly customizable engineered zinc finger protein. This chapter provides methods for modifying LITEZ to target new DNA sequences, engineering a programmable LED array to illuminate cell cultures, and using the modified LITEZ system to achieve spatiotemporal control of transgene expression in mammalian cells. PMID:24718797

  20. Exploring the impact of dysfunctional posttraumatic survival responses on crime revictimization.

    PubMed

    Kunst, Maarten Jacob Johannes; Winkel, Frans Willem

    2013-01-01

    This study investigated the association between posttraumatic stress disorder (PTSD) symptoms and repeat victimization across crime types in survivors of traumatic interpersonal violence. An evolutionary psychological perspective was adopted to propose that symptoms of hyperarousal (particularly hypervigilance, exaggerated startle response, and irritability or outbursts of anger) and numbing predict revictimization. These symptoms may act as manifestations of dysfunctional survival responses. Survival responses are adaptive in life-threatening situations but may work counter-productive in the absence of immediate threat. Participants were recruited through the Dutch Victim Compensation Fund (DVCF; N = 233). PTSD symptomatology was assessed between October and December 2007. Revictimization was measured 6 months later. Results were partly in line with expectations. Exaggerated startle response and symptoms of irritability or outbursts of anger but not hypervigilance and numbing were related to revictimization. PMID:24047046

  1. Survival and stress responses of E. coli exposed to alkaline cleaners

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies were undertaken to evaluate the effects of alkaline cleaners commonly used in food processing environments on survival and stress responses of the foodborne pathogen Escherichia coli O157:H7. Alkaline cleaners containing either sodium hydroxide or potassium hydroxide and hypochlorite had gre...

  2. Light induced self-written waveguides interactions in photopolymer media.

    PubMed

    Ben Belgacem, Mohamed; Kamoun, Saber; Gargouri, Mohamed; Honorat Dorkenoo, Kokou D; Barsella, Alberto; Mager, Loïc

    2015-08-10

    We present experimental and theoretical study of the interaction of Light Induced Self-Written (LISW) waveguides in photopolymers. We show that the diffusion of the monomer controls the refractive index distribution. Consequently it influences the interaction between the LISW channels allowing the observation of anti-crossing behavior or the propagation of an array of non interacting LISW waveguides. PMID:26367937

  3. EP300 Protects from Light-Induced Retinopathy in Zebrafish

    PubMed Central

    Kawase, Reiko; Nishimura, Yuhei; Ashikawa, Yoshifumi; Sasagawa, Shota; Murakami, Soichiro; Yuge, Mizuki; Okabe, Shiko; Kawaguchi, Koki; Yamamoto, Hiroshi; Moriyuki, Kazumi; Yamane, Shinsaku; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Tanaka, Toshio

    2016-01-01

    Exposure of rhodopsin to bright white light can induce photoreceptor cell damage and degeneration. However, a comprehensive understanding of the mechanisms underlying light-induced retinopathy remains elusive. In this study, we performed comparative transcriptome analysis of three rodent models of light-induced retinopathy, and we identified 37 genes that are dysregulated in all three models. Gene ontology analysis revealed that this gene set is significantly associated with a cytokine signaling axis composed of signal transducer and activator of transcription 1 and 3 (STAT1/3), interleukin 6 signal transducer (IL6ST), and oncostatin M receptor (OSMR). Furthermore, the analysis suggested that the histone acetyltransferase EP300 may be a key upstream regulator of the STAT1/3–IL6ST/OSMR axis. To examine the role of EP300 directly, we developed a larval zebrafish model of light-induced retinopathy. Using this model, we demonstrated that pharmacological inhibition of EP300 significantly increased retinal cell apoptosis, decreased photoreceptor cell outer segments, and increased proliferation of putative Müller cells upon exposure to intense light. These results suggest that EP300 may protect photoreceptor cells from light-induced damage and that activation of EP300 may be a novel therapeutic approach for the treatment of retinal degenerative diseases. PMID:27242532

  4. Predator functional response and prey survival: Direct and indirect interactions affecting a marked prey population

    USGS Publications Warehouse

    Miller, David A.; Grand, J.B.; Fondell, T.F.; Anthony, M.

    2006-01-01

    1. Predation plays an integral role in many community interactions, with the number of predators and the rate at which they consume prey (i.e. their functional response) determining interaction strengths. Owing to the difficulty of directly observing predation events, attempts to determine the functional response of predators in natural systems are limited. Determining the forms that predator functional responses take in complex systems is important in advancing understanding of community interactions. 2. Prey survival has a direct relationship to the functional response of their predators. We employed this relationship to estimate the functional response for bald eagle Haliaeetus leucocepalus predation of Canada goose Branta canadensis nests. We compared models that incorporated eagle abundance, nest abundance and alternative prey presence to determine the form of the functional response that best predicted intra-annual variation in survival of goose nests. 3. Eagle abundance, nest abundance and the availability of alternative prey were all related to predation rates of goose nests by eagles. There was a sigmoidal relationship between predation rate and prey abundance and prey switching occurred when alternative prey was present. In addition, predation by individual eagles increased as eagle abundance increased. 4. A complex set of interactions among the three species examined in this study determined survival rates of goose nests. Results show that eagle predation had both prey- and predator-dependent components with no support for ratio dependence. In addition, indirect interactions resulting from the availability of alternative prey had an important role in mediating the rate at which eagles depredated nests. As a result, much of the within-season variation in nest survival was due to changing availability of alternative prey consumed by eagles. 5. Empirical relationships drawn from ecological theory can be directly integrated into the estimation process to

  5. Role of space charges on light-induced effects in nematic liquid crystals doped by methyl red

    NASA Astrophysics Data System (ADS)

    Lucchetti, L.; Simoni, F.

    2014-03-01

    We show that both the extraordinarily large nonlinear response and the light-induced permanent reorientation in liquid crystals doped by the azo dye methyl red originates from the same phenomenon of modification of the charge density on the irradiated surface. The demonstration is done by applying ac voltage to the samples, showing that in this case no permanent anchoring is possible. The measurements confirm the role of photoisomerization that gives a transient contribution to the actual reorientation process only in the high dose regime. This result allows us to draw a picture for light-induced effects that might be applied to a large class of compounds.

  6. Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice*S⃞

    PubMed Central

    Maeda, Akiko; Maeda, Tadao; Golczak, Marcin; Chou, Steven; Desai, Amar; Hoppel, Charles L.; Matsuyama, Shigemi; Palczewski, Krzysztof

    2009-01-01

    Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration. PMID:19304658

  7. Identification of novel light-induced genes in the suprachiasmatic nucleus

    PubMed Central

    Porterfield, Veronica M; Piontkivska, Helen; Mintz, Eric M

    2007-01-01

    Background The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice. Results The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose) polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements. Conclusion The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders. PMID:18021443

  8. Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.

    PubMed

    Burén, Stefan; Gomes, Ana L; Teijeiro, Ana; Fawal, Mohamad-Ali; Yilmaz, Mahmut; Tummala, Krishna S; Perez, Manuel; Rodriguez-Justo, Manuel; Campos-Olivas, Ramón; Megías, Diego; Djouder, Nabil

    2016-08-01

    Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations. PMID:27505673

  9. Blue and green light-induced phototropism in Arabidopsis thaliana and Lactuca sativa L. seedlings

    SciTech Connect

    Steinitz, B.; Ren, Z.; Poff, K.L.

    1985-01-01

    Exposure time-response curves for blue and green light-induced phototropic bending in hypocotyls of Arabidopsis thaliana (L.) Heynh. and Lactuca sativa L. seedlings are presented. These seedlings show significant phototropic sensitivity up to 540 to 550 nanometers. Since wavelengths longer than 560 nanometers do not induce phototropic bending, it is suggested that the response to 510 to 550 nanometers light is mediated by the specific blue light photoreceptor of phototropism. The authors advise care in the use of green safelights for studies of phototropism.

  10. Pathological and immunological responses associated with differential survival of Chinook salmon following Renibacterium salmoninarum challenge

    USGS Publications Warehouse

    Purcell, Maureen K.; Elliott, Diane G.; Metzger, C. David; Wargo, Andrew; Park, K. Linda

    2010-01-01

    Chinook salmon Oncorhynchus tshawytscha are highly susceptible to Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD). Previously we demonstrated that introduced Chinook salmon from Lake Michigan, Wisconsin (WI), USA, have higher survival following R. salmoninarum challenge relative to the progenitor stock from Green River, Washington, USA. In the present study, we investigated the pathological and immunological responses that are associated with differential survival in the 2 Chinook salmon stocks following intra-peritoneal R. salmoninarum challenge of 2 different cohort years (2003 and 2005). Histological evaluation revealed delayed appearance of severe granulomatous lesions in the kidney and lower overall prevalence of membranous glomerulopathy in the higher surviving WI stock. The higher survival WI stock had a lower bacterial load at 28 d post-infection, as measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). However, at all other time points, bacterial load levels were similar despite higher mortality in the more susceptible Green River stock, suggesting the possibility that the stocks may differ in their tolerance to infection by the bacterium. Interferon-y, inducible nitric oxide synthase (iNOS), Mx-1, and transferrin gene expression were up-regulated in both stocks following challenge. A trend of higher iNOS gene expression at later time points (≥28 d post-infection) was observed in the lower surviving Green River stock, suggesting the possibility that higher iNOS expression may contribute to greater pathology in that stock.

  11. Pathological and immunological responses associated with differential survival of Chinook salmon following Renibacterium salmoninarum challenge.

    PubMed

    Metzger, David C; Elliott, Diane G; Wargo, Andrew; Park, Linda K; Purcell, Maureen K

    2010-05-18

    Chinook salmon Oncorhynchus tshawytscha are highly susceptible to Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD). Previously we demonstrated that introduced Chinook salmon from Lake Michigan, Wisconsin (WI), USA, have higher survival following R. salmoninarum challenge relative to the progenitor stock from Green River, Washington, USA. In the present study, we investigated the pathological and immunological responses that are associated with differential survival in the 2 Chinook salmon stocks following intra-peritoneal R. salmoninarum challenge of 2 different cohort years (2003 and 2005). Histological evaluation revealed delayed appearance of severe granulomatous lesions in the kidney and lower overall prevalence of membranous glomerulopathy in the higher surviving WI stock. The higher survival WI stock had a lower bacterial load at 28 d post-infection, as measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). However, at all other time points, bacterial load levels were similar despite higher mortality in the more susceptible Green River stock, suggesting the possibility that the stocks may differ in their tolerance to infection by the bacterium. Interferon-gamma, inducible nitric oxide synthase (iNOS), Mx-1, and transferrin gene expression were up-regulated in both stocks following challenge. A trend of higher iNOS gene expression at later time points (> or = 28 d post-infection) was observed in the lower surviving Green River stock, suggesting the possibility that higher iNOS expression may contribute to greater pathology in that stock. PMID:20597428

  12. UV light induces premature senescence in Akt1-null mouse embryonic fibroblasts by increasing intracellular levels of ROS

    SciTech Connect

    Jee, Hye Jin; Kim, Hyun-Ju; Kim, Ae Jeong; Bae, Yoe-Sik; Bae, Sun Sik; Yun, Jeanho

    2009-06-05

    Akt/PKB plays a pivotal role in cell survival and proliferation. Previously, we reported that UV-irradiation induces extensive cell death in Akt2{sup -/-} mouse embryonic fibroblasts (MEFs) while Akt1{sup -/-} MEFs show cell cycle arrest. Here, we find that Akt1{sup -/-} MEFs exhibit phenotypic changes characteristics of senescence upon UV-irradiation. An enlarged and flattened morphology, a reduced cell proliferation and an increased senescence-associated {beta}-galactosidase (SA {beta}-gal) staining indicate that Akt1{sup -/-} MEFs undergo premature senescence after UV-irradiation. Restoring Akt1 expression in Akt1{sup -/-} MEFs suppressed SA {beta}-gal activity, indicating that UV-induced senescence is due to the absence of Akt1 function. Notably, levels of ROS were rapidly increased upon UV-irradiation and the ROS scavenger NAC inhibits UV-induced senescence of Akt1{sup -/-} MEFs, suggesting that UV light induces premature senescence in Akt1{sup -/-} MEFs by modulating intracellular levels of ROS. In conjunction with our previous work, this indicates that different isoforms of Akt have distinct function in response to UV-irradiation.

  13. Factors that affect response to chemotherapy and survival of patients with advanced head and neck cancer.

    PubMed

    Amer, M H; Al-Sarraf, M; Vaitkevicius, V K

    1979-06-01

    A review of 164 patients with far advanced head and neck cancer, treated by a cytotoxic chemotherapy over a ten year period, at WAyne State University, Detroit, Michigan, was done in an attempt to determine factors that may influence the response to chemotherapy and subsequent survival. Response rate to methotrexate was 28%, 5-FU 31%, and porfiromycin 13%. Improved responses were noted with combination chemotherapy. Patients who failed to first line therapy rarely responded to other single agent or combination chemotherapy. Those who did not have prior surgery and/or radiotherapy had better results from drug therapy. Patients with good performance status at the time of initial chemotherapy, had better response to treatment (32% vs. 13% PR & CR) and longer survival (28 weeks vs. 9 weeks, p = 0.01) when compared to those with poor status. Patients who responded to chemotherapy have better survival compared to nonresponders (29 weeks vs. 16 weeks, p = 0.002). This information may prove helpful in future planning of multidisciplinary approach in the treatment of patients with head and neck cancer. PMID:455217

  14. Transcriptional responses to fluctuating thermal regimes underpinning differences in survival in the solitary bee Megachile rotundata.

    PubMed

    Torson, Alex S; Yocum, George D; Rinehart, Joseph P; Kemp, William P; Bowsher, Julia H

    2015-04-01

    The transcriptional responses of insects to long-term, ecologically relevant temperature stress are poorly understood. Long-term exposure to low temperatures, commonly referred to as chilling, can lead to physiological effects collectively known as chill injury. Periodically increasing temperatures during long-term chilling has been shown to increase survival in many insects. However, the transcripts responsible for this increase in survival have never been characterized. Here, we present the first transcriptome-level analysis of increased longevity under fluctuating temperatures during chilling. Overwintering post-diapause quiescent alfalfa leafcutting bees (Megachile rotundata) were exposed to a constant temperature of 6°C, or 6°C with a daily fluctuation to 20°C. RNA was collected at two different time points, before and after mortality rates began to diverge between temperature treatments. Expression analysis identified differentially regulated transcripts between pairwise comparisons of both treatments and time points. Transcripts functioning in ion homeostasis, metabolic pathways and oxidative stress response were up-regulated in individuals exposed to periodic temperature fluctuations during chilling. The differential expression of these transcripts provides support for the hypotheses that fluctuating temperatures protect against chill injury by reducing oxidative stress and returning ion concentrations and metabolic function to more favorable levels. Additionally, exposure to fluctuating temperatures leads to increased expression of transcripts functioning in the immune response and neurogenesis, providing evidence for additional mechanisms associated with increased survival during chilling in M. rotundata. PMID:25657206

  15. Phytochromes A and B mediate red-light-induced positive phototropism in roots

    NASA Technical Reports Server (NTRS)

    Kiss, John Z.; Mullen, Jack L.; Correll, Melanie J.; Hangarter, Roger P.

    2003-01-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30 degrees to 40 degrees, compared with 5 degrees to 10 degrees without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants.

  16. Relationship between tumor response and survival following radiotherapy for carcinoma of the bronchus

    SciTech Connect

    Saunders, M.I.; Barltrop, M.A.; Rassa, P.M.; Anderson, P.J.; Dische, S.

    1984-04-01

    Tumor response was closely observed in a randomized controlled trial of a radiosensitizing drug in the radiotherapy of carcinoma of the bronchus. The persistence of tumor cells in the sputum after treatment and the degree of regression measured radiologically at two months did not correlate with the subsequent course. However, total regression of tumor and time to regrowth both assessed radiologically showed a highly significant correlation with survival.

  17. An unusual response with long term survival using erlotinib in NSCLC lung with brain metastases.

    PubMed

    Rastogi, Madhup; Nanda, Sambit Swarup; Prakash, Chandra; Kulshreshtha, Dinkar

    2016-01-01

    We present a case of a middle-aged woman with adenocarcinoma of the lung and metastatic brain lesions. In view of her poor general condition and poor compliance to first-line chemotherapy, the patient was kept on tablet erlotinib after whole brain radiotherapy. This novel treatment resulted in a dramatic response with radiological regression in both the primary lung lesion and metastatic intracranial lesions translating in unexpected and ongoing 24-month survival. PMID:26729829

  18. Divergence of the Response Induced by Xenogenic Immunization in the Sepsis Survival of Rats

    PubMed Central

    Perez-Cruz, Magdiel; Costa, Cristina; Manez, Rafael

    2015-01-01

    We have previously described that boosted natural xenoantibodies in rats cross-react to bacteria by targeting carbohydrate antigens. This type of immunization is associated with reduced survival after cecal ligation and puncture (CLP). In the present study, we investigated further this phenomenon by immunizing Lewis rats with three intraperitoneal injections, every other day, of hamster blood compared to saline-injected control animals. One day after the last injection, CLP was performed to produce a low-grade sepsis. Induction of xenoantibodies was associated with a reduction in animal survival after CLP relative to controls (45% vs. 90%, p<0.01). No bacterial blood load was observed after CLP in this model either with or without xenoantibody enhancement, indicating that the augmented mortality was not mediated by a direct effect of boosted xenoantibodies over blood bacteria. Nevertheless, the xenoimmunization produced a systemic inflammatory response in all rats. Additionally, a lack of weight gain at the time of CLP was present in animals that died after the procedure, which was not observed in surviving rats and controls. The cytokine profile at the time of CLP in animals that died after the procedure was characterized by an increase in the serum level of several cytokines, particularly adipokines. In contrast, the cytokine profile at CLP of xenoimmunized rats that survived the procedure was characterized by a reduction in the level of cytokines. In conclusion, this study failed to show a direct effect of boosted xenoantibodies over blood bacterial isolates as cause for the decreased survival after CLP. However, it evidenced that non-infectious systemic inflammation may lead to a pattern of augmented cytokines, particularly adipokines, which impairs survival after subsequent CLP. Therefore, the profile of cytokines existing before the infectious insult appears more crucial than that resulting from the condition for the outcome of sepsis. PMID:25984763

  19. JAK/STAT signalling mediates cell survival in response to tissue stress.

    PubMed

    La Fortezza, Marco; Schenk, Madlin; Cosolo, Andrea; Kolybaba, Addie; Grass, Isabelle; Classen, Anne-Kathrin

    2016-08-15

    Tissue homeostasis relies on the ability of tissues to respond to stress. Tissue regeneration and tumour models in Drosophila have shown that c-Jun amino-terminal kinase (JNK) acts as a prominent stress-response pathway promoting injury-induced apoptosis and compensatory proliferation. A central question remaining unanswered is how both responses are balanced by activation of a single pathway. Signalling through the Janus kinase/Signal transducers and activators of transcription (JAK/STAT) pathway, which is a potential JNK target, is implicated in promoting compensatory proliferation. While we observe JAK/STAT activation in imaginal discs upon damage, our data demonstrate that JAK/STAT and its downstream effector Zfh2 promote the survival of JNK signalling cells. The JNK component fos and the pro-apoptotic gene hid are regulated in a JAK/STAT-dependent manner. This molecular pathway restrains JNK-induced apoptosis and spatial propagation of JNK signalling, thereby limiting the extent of tissue damage, as well as facilitating systemic and proliferative responses to injury. We find that the pro-survival function of JAK/STAT also drives tumour growth under conditions of chronic stress. Our study defines the function of JAK/STAT in tissue stress and illustrates how crosstalk between conserved signalling pathways establishes an intricate equilibrium between proliferation, apoptosis and survival to restore tissue homeostasis. PMID:27385008

  20. Nanoparticle-Mediated, Light-Induced Phase Separations.

    PubMed

    Neumann, Oara; Neumann, Albert D; Silva, Edgar; Ayala-Orozco, Ciceron; Tian, Shu; Nordlander, Peter; Halas, Naomi J

    2015-12-01

    Nanoparticles that both absorb and scatter light, when dispersed in a liquid, absorb optical energy and heat a reduced fluid volume due to the combination of multiple scattering and optical absorption. This can induce a localized liquid-vapor phase change within the reduced volume without the requirement of heating the entire fluid. For binary liquid mixtures, this process results in vaporization of the more volatile component of the mixture. When subsequently condensed, these two steps of vaporization and condensation constitute a distillation process mediated by nanoparticles and driven by optical illumination. Because it does not require the heating of a large volume of fluid, this process requires substantially less energy than traditional distillation using thermal sources. We investigated nanoparticle-mediated, light-induced distillation of ethanol-H2O and 1-propanol-H2O mixtures, using Au-SiO2 nanoshells as the absorber-scatterer nanoparticle and nanoparticle-resonant laser irradiation to drive the process. For ethanol-H2O mixtures, the mole fraction of ethanol obtained in the light-induced process is substantially higher than that obtained by conventional thermal distillation, essentially removing the ethanol-H2O azeotrope that limits conventional distillation. In contrast, for 1-propanol-H2O mixtures the distillate properties resulting from light-induced distillation were very similar to those obtained by thermal distillation. In the 1-propanol-H2O system, a nanoparticle-mediated, light-induced liquid-liquid phase separation was also observed. PMID:26535465

  1. Light-induced anodisation of silicon for solar cell passivation

    NASA Astrophysics Data System (ADS)

    Cui, J.; Wang, X.; Opila, R.; Lennon, A.

    2013-11-01

    This paper reports a new method for forming anodic oxides on silicon surfaces using the light-induced current of pn-junction solar cells to make p-type silicon surfaces anodic. The light-induced anodisation process enables anodic oxide layers as thick as 79 nm to be formed at room temperature in a faster, more uniform, and controllable manner compared to previously reported clip-based anodisation methods. Although the effective minority carrier lifetime decreased immediately after light-induced anodisation from initial values measured with an 17 nm thermally grown oxide on both wafer surfaces, the 1-sun implied open circuit voltage of wafers on which the thermally grown oxide on the p-type surface was replaced by an anodic oxide of the same thickness could be returned to its initial value of ˜635 mV (for 3-5 Ω-cm Cz silicon wafers) after a 400 °C anneal in oxygen and then forming gas. The passivation of the formed anodic oxide layers was stable for a period of 50 days providing the oxide was protected by a 75 nm thick silicon nitride capping layer.

  2. Modulation of Dendritic Cell Responses by Parasites: A Common Strategy to Survive

    PubMed Central

    Terrazas, César A.; Terrazas, Luis I.; Gómez-García, Lorena

    2010-01-01

    Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved. PMID:20204070

  3. Influence of saliva-coating on the ultraviolet-light-induced photocatalytic bactericidal effects on modified titanium surfaces

    NASA Astrophysics Data System (ADS)

    Lee, Jeong-Eun; Park, So-Yoon; Chang, Young-Il; Lim, Young-Jun; Ahn, Sug-Joon

    2012-07-01

    The purpose of this study was to investigate the ultraviolet-light-induced photocatalytic bactericidal effects of titanium surfaces on Streptococcus sanguinis in the presence of saliva-coating. Three different titanium disks were prepared: machined (MA), heat-treated (HT), and anodized surfaces (AO). Each disk was incubated with whole saliva or phosphate-buffered saline for 2 h. Antibacterial tests were performed by incubating a S. sanguinis suspension with each disk for 90 or 180 min under ultraviolet (UV) illumination. The viable counts of bacteria were enumerated from the cell suspension and the UV-light-induced photocatalytic bactericidal effects were determined by the bacterial survival rate. Without saliva-coating, AO disks exhibited significantly decreased bacterial survival rates compared to MA disks. The bacterial survival rates of the HT disks were intermediate between MA and AO in the absence of saliva-coating. However, saliva-coating significantly increased bacterial survival rates in all surface types. There was no significant difference in bacterial survival rates among the three surface types after saliva-coating. This study suggests that Ti-based antibacterial implant materials using TiO2 photocatalyst may have a limitation for intraoral use.

  4. Survival Response and Rearrangement of Plasmid DNA of Lactococcus lactis during Long-Term Starvation

    PubMed Central

    Kim, Woojin S.; Park, Ji Hyeon; Ren, Jun; Su, Ping; Dunn, Noel W.

    2001-01-01

    The survival response of Lactococcus lactis during long-term starvation was investigated. The cells were cultured with different levels of glucose (the sole energy source) and either were kept in the resultant spent medium or transferred to fresh medium (without glucose) for up to 2 years. The survival of the cells during starvation was not dependent on the nature of transition phase, as expected, but on the nature of medium in which the cells were kept. The proliferation of cells, despite the apparent lack of glucose, could have been due to some cells being able to utilize the small amounts of peptides still present in the spent medium or to use energy sources provided by the breakup of dead cells. The 1- and 2-year-old cultures contained cells with vastly changed morphotypes. When these isolates were examined, it was revealed that the original plasmids present in the parent were rearranged in a certain way, and an entirely new plasmid was generated. Changes were also evident in the chromosomal DNA and in gene expression. Furthermore, all of the isolates exhibited a growth advantage relative to the parent cells when grown in energy-limiting media. When they were tested against different types of stresses, they exhibited a higher resistance against the bile salt and hydrogen peroxide stresses compared to the parent. Because of the similar changes observed in the 2-year-old isolates, a similar survival strategy may be operational in those cells that survive for that length of time. PMID:11571161

  5. Surviving the acid barrier: responses of pathogenic Vibrio cholerae to simulated gastric fluid.

    PubMed

    Singh, Atheesha; Barnard, Tobias G

    2016-01-01

    When bacteria are subjected to low acidic pHs of the gastric environment, they may enter the viable but nonculturable (VBNC) state of survival. In this state, bacteria cannot be cultured on solid media, still exhibit signs of metabolic activity (viability). In this study, the response of pathogenic Vibrio cholerae O1 and O139 to low pH-simulated environments of the human stomach was evaluated for their survival by culturability (plate count) and viability (flow cytometry-FC) assays. Bacteria were acid challenged with simulated gastric fluid (SGF) at pH 1.5, 2.5, 3.5 and 4.5 over a period of 180 min. Exposure to SGF up to 120 min increased acid tolerance of the Vibrios up to pH 3.5 with acid challenge occurring at pH 4.5. Bacteria were culturable from pH 2.5 to 4.5 up to 60 min SGF exposure. The stationary-phase cultures of Vibrio were able to survive SGF at all pHs in an 'injured' state with FC. This could possibly mean that the bacteria have entered the VBNC stage of survival. This is a worrying public health concern due to the fact that once favourable conditions arise (intestines), these Vibrios can change back to an infectious state and cause disease. PMID:26496916

  6. Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer

    SciTech Connect

    Jayachandran, Priya; Pai, Reetesh K.; Quon, Andrew; Graves, Edward; Krakow, Trevor E.; La, Trang; Loo, Billy W.; Koong, Albert C.; Chang, Daniel T.

    2012-10-01

    Purpose: To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer. Materials and Methods: The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum Multiplication-Sign 50%. The total glycolytic activity (TGA{sub x}) was defined as the mean SUV Multiplication-Sign MTV{sub x}. The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale. Results: The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV{sub 2.5Post} and TGA{sub 2.5Post} had the greatest correlation. The MTV{sub 2} ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001). Conclusion: The maximum SUV was not a predictive or prognostic parameter. The MTV{sub 2.5} and TGA{sub 2.5} were useful markers for predicting the response and

  7. Light-Induced Resistance Effect Observed in Nano Au Films Covered Two-Dimensional Colloidal Crystals.

    PubMed

    Liu, Shuai; Huang, Meizhen; Yao, Yanjie; Wang, Hui; Jin, Kui-juan; Zhan, Peng; Wang, Zhenlin

    2015-09-01

    Tailoring resistance response using periodic nanostructures is one of the key issues in the current research. Two-dimensional colloidal crystals (CCs) structure is one of popular periodic nanospheres' structures and most of reports are focused on anomalous transmission of light or biomedical applications. In this work, a light-induced resistance effect is observed on silicon-based Au films covered CCs, featuring a remarkable resistance change as much as 56% and resistance switching characteristic. The diffusion and recombination of photocarriers is the crucial factor for this effect. This finding will expand photoelectricity functionality and be useful for future development of CC-based photoelectric devices. PMID:26314930

  8. Involvement of Ras in survival responsiveness to nitric oxide toxicity in pheochromocytoma cells.

    PubMed

    Jeong, Hyun Sik; Kim, Seong Won; Baek, Kwang Jin; Lee, Hee Sung; Kwon, Nyoun Soo; Kim, Young-Myeong; Yun, Hye-Young

    2002-11-01

    Nitric oxide (NO) plays a key role in attenuation of tumor growth by activated macrophages that generate large amount of cytotoxic/cytostatic free radicals. However, some tumor cells may survive from NO cytotoxicity and continue to proliferate to malignant tumors. Since a protooncogene product Ras was shown to be activated by NO, this study investigated the involvement of Ras in the cell survival in response to NO cytotoxicity in pheochromocytoma (PC12) cells. Treatment with Ras inhibitor or constitutive expression of dominant negative Ras markedly increased NO-induced cell death. NO-resistant PC12 cells (PC12-NO-R) exhibited higher steady state Ras activity than the parental PC12 cells. Inducible expression using tetracycline-on (Tet-on) system of Ras mutants (dominant negative Ras or dominant active Ras) demonstrated that blockade of Ras activity increased NO-induced cell death whereas enhancement of Ras activity attenuated NO-induced cell death. Furthermore, inducible expression of NO-insensitive mutant Ras selectively increased cellular vulnerability to NO but not to ROS. NO, Ras inhibitor and extracellular signal-regulated kinase (Erk) blocker synergistically increased cell death. These observations suggest that Ras activity may be a critical factor for survival response of tumor cells to NO toxicity and pharmacological agents affecting Ras activity may enhance efficacy of NO-mediated tumor therapies. PMID:12635656

  9. Survival, growth and stress response of juvenile tidewater goby, Eucyclogobius newberryi, to interspecific competition for food

    PubMed Central

    Chase, Daniel A.; Flynn, Erin E.; Todgham, Anne E.

    2016-01-01

    Reintroduction of endangered fishes to historic habitat has been used as a recovery tool; however, these fish may face competition from other fishes that established in their native habitat since extirpation. This study investigated the physiological response of tidewater goby, Eucyclogobius newberryi, an endangered California fish, when competing for food with threespine stickleback, Gasterosteus aculeatus, a native species, and rainwater killifish, Lucania parva, a non-native species. Survival, growth and physiological indicators of stress (i.e. cortisol, glucose and lactate concentrations) were assessed for juvenile fish held for 28 days in two food-limited conditions. When fed a 75% ration, survival of E. newberryi was significantly lower when held with G. aculeatus. In all fish assemblages, weight and relative condition decreased then stabilized over the 28 day experiment, while length remained unchanged. Whole-body cortisol in E. newberryi was not affected by fish assemblage; however, glucose and lactate concentrations were significantly higher with conspecifics than with other fish assemblages. When fed a 50% ration, survival of E. newberryi decreased during the second half of the experiment, while weight and relative condition decreased and length remained unchanged in all three fish assemblages. Cortisol concentrations were significantly higher for all fish assemblages compared with concentrations at the start of the experiment, whereas glucose and lactate concentrations were depressed relative to concentrations at the start of the experiment, with the magnitude of decrease dependent on the species assemblage. Our findings indicate that E. newberryi exhibited reduced growth and an elevated generalized stress response during low food availability. In response to reduced food availability, competition with G. aculeatus had the greatest physiological effect on E. newberryi, with minimal effects from the non-native L. parva. This study presents the first

  10. Survival, growth and stress response of juvenile tidewater goby, Eucyclogobius newberryi, to interspecific competition for food.

    PubMed

    Chase, Daniel A; Flynn, Erin E; Todgham, Anne E

    2016-01-01

    Reintroduction of endangered fishes to historic habitat has been used as a recovery tool; however, these fish may face competition from other fishes that established in their native habitat since extirpation. This study investigated the physiological response of tidewater goby, Eucyclogobius newberryi, an endangered California fish, when competing for food with threespine stickleback, Gasterosteus aculeatus, a native species, and rainwater killifish, Lucania parva, a non-native species. Survival, growth and physiological indicators of stress (i.e. cortisol, glucose and lactate concentrations) were assessed for juvenile fish held for 28 days in two food-limited conditions. When fed a 75% ration, survival of E. newberryi was significantly lower when held with G. aculeatus. In all fish assemblages, weight and relative condition decreased then stabilized over the 28 day experiment, while length remained unchanged. Whole-body cortisol in E. newberryi was not affected by fish assemblage; however, glucose and lactate concentrations were significantly higher with conspecifics than with other fish assemblages. When fed a 50% ration, survival of E. newberryi decreased during the second half of the experiment, while weight and relative condition decreased and length remained unchanged in all three fish assemblages. Cortisol concentrations were significantly higher for all fish assemblages compared with concentrations at the start of the experiment, whereas glucose and lactate concentrations were depressed relative to concentrations at the start of the experiment, with the magnitude of decrease dependent on the species assemblage. Our findings indicate that E. newberryi exhibited reduced growth and an elevated generalized stress response during low food availability. In response to reduced food availability, competition with G. aculeatus had the greatest physiological effect on E. newberryi, with minimal effects from the non-native L. parva. This study presents the first

  11. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis

    PubMed Central

    Liang, DongYu; Hou, YanQiang; Lou, XiaoLi; Chen, HongWei

    2015-01-01

    Purpose Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Results Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Conclusions Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis. PMID:26121476

  12. Burkholderia pseudomallei Differentially Regulates Host Innate Immune Response Genes for Intracellular Survival in Lung Epithelial Cells

    PubMed Central

    Vellasamy, Kumutha Malar; Mariappan, Vanitha; Shankar, Esaki M.; Vadivelu, Jamuna

    2016-01-01

    Background Burkholderia pseudomallei, the causative agent of melioidosis poses a serious threat to humankind. B. pseudomallei secretes numerous virulence proteins that alter host cell functions to escape from intracellular immune sensors. However, the events underlying disease pathogenesis are poorly understood. Methods We determined the ability of B. pseudomallei to invade and survive intracellularly in A549 human lung epithelial cells, and also investigated the early transcriptional responses using an Illumina HumanHT-12 v4 microarray platform, after three hours of exposure to live B. pseudomallei (BCMS) and its secreted proteins (CCMS). Results We found that the ability of B. pseudomallei to invade and survive intracellularly correlated with increase of multiplicity of infection and duration of contact. Activation of host carbohydrate metabolism and apoptosis as well as suppression of amino acid metabolism and innate immune responses both by live bacteria and its secreted proteins were evident. These early events might be linked to initial activation of host genes directed towards bacterial dissemination from lungs to target organs (via proposed in vivo mechanisms) or to escape potential sensing by macrophages. Conclusion Understanding the early responses of A549 cells toward B. pseudomallei infection provide preliminary insights into the likely pathogenesis mechanisms underlying melioidosis, and could contribute to development of novel intervention strategies to combat B. pseudomallei infections. PMID:27367858

  13. High Dietary Folate in Mice Alters Immune Response and Reduces Survival after Malarial Infection

    PubMed Central

    Meadows, Danielle N.; Bahous, Renata H.; Best, Ana F.; Rozen, Rima

    2015-01-01

    Malaria is a significant global health issue, with nearly 200 million cases in 2013 alone. Parasites obtain folate from the host or synthesize it de novo. Folate consumption has increased in many populations, prompting concerns regarding potential deleterious consequences of higher intake. The impact of high dietary folate on the host’s immune function and response to malaria has not been examined. Our goal was to determine whether high dietary folate would affect response to malarial infection in a murine model of cerebral malaria. Mice were fed control diets (CD, recommended folate level for rodents) or folic acid-supplemented diets (FASD, 10x recommended level) for 5 weeks before infection with Plasmodium berghei ANKA. Survival, parasitemia, numbers of immune cells and other infection parameters were assessed. FASD mice had reduced survival (p<0.01, Cox proportional hazards) and higher parasitemia (p< 0.01, joint model of parasitemia and survival) compared with CD mice. FASD mice had lower numbers of splenocytes, total T cells, and lower numbers of specific T and NK cell sub-populations, compared with CD mice (p<0.05, linear mixed effects). Increased brain TNFα immunoreactive protein (p<0.01, t-test) and increased liver Abca1 mRNA (p<0.01, t-test), a modulator of TNFα, were observed in FASD mice; these variables correlated positively (rs = 0.63, p = 0.01). Bcl-xl/Bak mRNA was increased in liver of FASD mice (p<0.01, t-test), suggesting reduced apoptotic potential. We conclude that high dietary folate increases parasite replication, disturbs the immune response and reduces resistance to malaria in mice. These findings have relevance for malaria-endemic regions, when considering anti-folate anti-malarials, food fortification or vitamin supplementation programs. PMID:26599510

  14. Three components in the light-induced current of the Limulus ventral photoreceptor.

    PubMed Central

    Deckert, A; Nagy, K; Helrich, C S; Stieve, H

    1992-01-01

    1. Light-induced currents were measured in Limulus ventral nerve photoreceptors using a two-electrode voltage clamp. Three kinetically distinct components in the light-induced current could be distinguished by varying the light adaptation state of the photoreceptor and the intensity of the stimulus light. 2. The components could be partly separated by choosing appropriate stimulus intensities and dark adaptation time. Thus the properties of the components could be separately studied. The first component is the first to recover after a light adaptation, appears temporally first in the light-induced response, has the lowest activation threshold and is the smallest. The second component needs a longer time to recover after an adapting illumination and its kinetics differ from that of the other components. Applying a bright stimulus to a dark-adapted cell a third component can be observed late in the response. 3. The time to peak of the first and the third components depended on the stimulus intensity, but not on the dark adaptation time. The time to peak of the second component became shorter the longer the dark adaptation time. For a constant adaptation state the time to the maximum of component 2 was independent, but those of components 1 and 3 were dependent on the membrane voltage. 4. To exclude the possibility of the contribution of voltage-gated currents, light-activated currents were measured at clamp potentials more negative than -50 mV after adding 4-aminopyridine into the bath solution or injecting tetraethyl-ammonium chloride into the cell. The properties of the three components remained unchanged under these conditions. 5. The I-V curve of the first component was flat at negative membrane potentials and had a strong outward rectification at positive membrane potentials. The I-V curve of component 3 showed a negative resistance at potentials more negative than about -30 mV. In contrast, the I-V curve for the second component was always nearly linear. 6. No

  15. Light-induced metastable structural changes in hydrogenated amorphous silicon

    SciTech Connect

    Fritzsche, H.

    1996-09-01

    Light-induced defects (LID) in hydrogenated amorphous silicon (a-Si:H) and its alloys limit the ultimate efficiency of solar panels made with these materials. This paper reviews a variety of attempts to find the origin of and to eliminate the processes that give rise to LIDs. These attempts include novel deposition processes and the reduction of impurities. Material improvements achieved over the past decade are associated more with the material`s microstructure than with eliminating LIDs. We conclude that metastable LIDs are a natural by-product of structural changes which are generally associated with non-radiative electron-hole recombination in amorphous semiconductors.

  16. Light-induced optomechanical forces in graphene waveguides

    NASA Astrophysics Data System (ADS)

    Guizal, Brahim; Antezza, Mauro

    2016-03-01

    We show that the electromagnetic forces generated by the excitations of a mode in graphene-based optomechanical systems are highly tunable by varying the graphene chemical potential, and orders of magnitude stronger than usual non-graphene-based devices, in both attractive and repulsive regimes. We analyze coupled waveguides made of two parallel graphene sheets, either suspended or supported by dielectric slabs, and study the interplay between the light-induced force and the Casimir-Lifshitz interaction. These findings pave the way to advanced possibilities of control and fast modulation for optomechanical devices and sensors at the nano- and microscales.

  17. Light-induced voltage alteration for integrated circuit analysis

    DOEpatents

    Cole, Jr., Edward I.; Soden, Jerry M.

    1995-01-01

    An apparatus and method are described for analyzing an integrated circuit (IC), The invention uses a focused light beam that is scanned over a surface of the IC to generate a light-induced voltage alteration (LIVA) signal for analysis of the IC, The LIVA signal may be used to generate an image of the IC showing the location of any defects in the IC; and it may be further used to image and control the logic states of the IC. The invention has uses for IC failure analysis, for the development of ICs, for production-line inspection of ICs, and for qualification of ICs.

  18. Light-induced voltage alteration for integrated circuit analysis

    DOEpatents

    Cole, E.I. Jr.; Soden, J.M.

    1995-07-04

    An apparatus and method are described for analyzing an integrated circuit (IC). The invention uses a focused light beam that is scanned over a surface of the IC to generate a light-induced voltage alteration (LIVA) signal for analysis of the IC. The LIVA signal may be used to generate an image of the IC showing the location of any defects in the IC; and it may be further used to image and control the logic states of the IC. The invention has uses for IC failure analysis, for the development of ICs, for production-line inspection of ICs, and for qualification of ICs. 18 figs.

  19. Preventing light-induced degradation in multicrystalline silicon

    SciTech Connect

    Lindroos, J. Boulfrad, Y.; Yli-Koski, M.; Savin, H.

    2014-04-21

    Multicrystalline silicon (mc-Si) is currently dominating the silicon solar cell market due to low ingot costs, but its efficiency is limited by transition metals, extended defects, and light-induced degradation (LID). LID is traditionally associated with a boron-oxygen complex, but the origin of the degradation in the top of the commercial mc-Si brick is revealed to be interstitial copper. We demonstrate that both a large negative corona charge and an aluminum oxide thin film with a built-in negative charge decrease the interstitial copper concentration in the bulk, preventing LID in mc-Si.

  20. Understanding Complete Pathologic Response in Oesophageal Cancer: Implications for Management and Survival

    PubMed Central

    O'Sullivan, K. E.; Hurley, E. T.; Hurley, J. P.

    2015-01-01

    Despite significant improvement over recent decades, oesophageal cancer survival rates remain poor. Neoadjuvant chemoradiotherapy followed by oesophageal resection is mainstay of therapy for resectable oesophageal tumours. Operative morbidity and mortality associated with oesophagectomy remain high and complications arise in up to 60% of patients. Management strategies have moved towards definitive chemoradiotherapy for a number of tumour sites (head and neck, cervical, and rectal) particularly for squamous pathology. We undertook to perform a review of the current status of morbidity and mortality associated with oesophagectomy, grading systems determining pathologic response, and data from clinical trials managing patients with definitive chemoradiotherapy to inform a discussion on the topic. PMID:26246803

  1. CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma.

    PubMed

    Dixit, Deobrat; Ahmad, Fahim; Ghildiyal, Ruchi; Joshi, Shanker Datt; Sen, Ellora

    2016-05-15

    Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4-AMPK axis to affect metabolic profile that has a strong bearing on their survival. PMID:27001465

  2. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    SciTech Connect

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  3. Light-induced defects in hybrid lead halide perovskite

    NASA Astrophysics Data System (ADS)

    Sharia, Onise; Schneider, William

    One of the main challenges facing organohalide perovskites for solar application is stability. Solar cells must last decades to be economically viable alternatives to traditional energy sources. While some causes of instability can be avoided through engineering, light-induced defects can be fundamentally limiting factor for practical application of the material. Light creates large numbers of electron and hole pairs that can contribute to degradation processes. Using ab initio theoretical methods, we systematically explore first steps of light induced defect formation in methyl ammonium lead iodide, MAPbI3. In particular, we study charged and neutral Frenkel pair formation involving Pb and I atoms. We find that most of the defects, except negatively charged Pb Frenkel pairs, are reversible, and thus most do not lead to degradation. Negative Pb defects create a mid-gap state and localize the conduction band electron. A minimum energy path study shows that, once the first defect is created, Pb atoms migrate relatively fast. The defects have two detrimental effects on the material. First, they create charge traps below the conduction band. Second, they can lead to degradation of the material by forming Pb clusters.

  4. Light-induced vegetative anthocyanin pigmentation in Petunia

    PubMed Central

    Albert, Nick W.; Lewis, David H.; Zhang, Huaibi; Irving, Louis J.; Jameson, Paula E.; Davies, Kevin M.

    2009-01-01

    The Lc petunia system, which displays enhanced, light-induced vegetative pigmentation, was used to investigate how high light affects anthocyanin biosynthesis, and to assess the effects of anthocyanin pigmentation upon photosynthesis. Lc petunia plants displayed intense purple anthocyanin pigmentation throughout the leaves and stems when grown under high-light conditions, yet remain acyanic when grown under shade conditions. The coloured phenotypes matched with an accumulation of anthocyanins and flavonols, as well as the activation of the early and late flavonoid biosynthetic genes required for flavonol and anthocyanin production. Pigmentation in Lc petunia only occurred under conditions which normally induce a modest amount of anthocyanin to accumulate in wild-type Mitchell petunia [Petunia axillaris×(Petunia axillaris×Petunia hybrida cv. ‘Rose of Heaven’)]. Anthocyanin pigmentation in Lc petunia leaves appears to screen underlying photosynthetic tissues, increasing light saturation and light compensation points, without reducing the maximal photosynthetic assimilation rate (Amax). In the Lc petunia system, where the bHLH factor Leaf colour is constitutively expressed, expression of the bHLH (Lc) and WD40 (An11) components of the anthocyanin regulatory system were not limited, suggesting that the high-light-induced anthocyanin pigmentation is regulated by endogenous MYB transcription factors. PMID:19380423

  5. Laser Phototherapy Enhances Mesenchymal Stem Cells Survival in Response to the Dental Adhesives

    PubMed Central

    Marques, Márcia Martins

    2015-01-01

    Background. We investigated the influence of laser phototherapy (LPT) on the survival of human mesenchymal stem cells (MSCs) submitted to substances leached from dental adhesives. Method. MSCs were isolated and characterized. Oral mucosa fibroblasts and osteoblast-like cells were used as comparative controls. Cultured medium conditioned with two adhesive systems was applied to the cultures. Cell monolayers were exposed or not to LPT. Laser irradiations were performed using a red laser (GaAlAs, 780 nm, 0.04 cm2, 40 mW, 1 W/cm2, 0.4 J, 10 seconds, 1 point, 10 J/cm2). After 24 h, cell viability was assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction assay. Data were statistically compared by ANOVA followed by Tukey's test (P < 0.05). Results. Different cell types showed different viabilities in response to the same materials. Substances leached from adhesives were less cytotoxic to MSCs than to other cell types. Substances leached from Clearfil SE Bond were highly cytotoxic to all cell types tested, except to the MSCs when applied polymerized and in association with LPT. LPT was unable to significantly increase the cell viability of fibroblasts and osteoblast-like cells submitted to the dental adhesives. Conclusion. LPT enhances mesenchymal stem cells survival in response to substances leached from dental adhesives. PMID:25879065

  6. Superantigens subvert the neutrophil response to promote abscess formation and enhance Staphylococcus aureus survival in vivo.

    PubMed

    Xu, Stacey X; Gilmore, Kevin J; Szabo, Peter A; Zeppa, Joseph J; Baroja, Miren L; Haeryfar, S M Mansour; McCormick, John K

    2014-09-01

    Staphylococcus aureus is a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection with S. aureus Newman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection by sea knockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b(+) Ly6G(+) neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently in S. aureus Newman-infected livers than in livers infected with the Newman sea knockout strain, promoting the survival of S. aureus in vivo. This represents a novel mechanism during infection whereby S. aureus utilizes SAgs to form a specialized niche and manipulate the immune system. PMID:24914221

  7. Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus Survival In Vivo

    PubMed Central

    Xu, Stacey X.; Gilmore, Kevin J.; Szabo, Peter A.; Zeppa, Joseph J.; Baroja, Miren L.; Haeryfar, S. M. Mansour

    2014-01-01

    Staphylococcus aureus is a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection with S. aureus Newman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection by sea knockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b+ Ly6G+ neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently in S. aureus Newman-infected livers than in livers infected with the Newman sea knockout strain, promoting the survival of S. aureus in vivo. This represents a novel mechanism during infection whereby S. aureus utilizes SAgs to form a specialized niche and manipulate the immune system. PMID:24914221

  8. Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

    PubMed Central

    DeNardo, David G.; Brennan, Donal J.; Rexhepaj, Elton; Ruffell, Brian; Shiao, Stephen L.; Madden, Stephen F.; Gallagher, William M.; Wadhwani, Nikhil; Keil, Scott D.; Junaid, Sharfaa A.; Rugo, Hope S.; Hwang, E. Shelley; Jirström, Karin; West, Brian L.; Coussens, Lisa M.

    2011-01-01

    Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)–dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor–bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell–dependent manner. These data provide a rationale for targeting macrophage recruitment/ response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. PMID:22039576

  9. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  10. The mechanism of color change in the neon tetra fish: a light-induced tunable photonic crystal array.

    PubMed

    Gur, Dvir; Palmer, Benjamin A; Leshem, Ben; Oron, Dan; Fratzl, Peter; Weiner, Steve; Addadi, Lia

    2015-10-12

    The fresh water fish neon tetra has the ability to change the structural color of its lateral stripe in response to a change in the light conditions, from blue-green in the light-adapted state to indigo in the dark-adapted state. The colors are produced by constructive interference of light reflected from stacks of intracellular guanine crystals, forming tunable photonic crystal arrays. We have used micro X-ray diffraction to track in time distinct diffraction spots corresponding to individual crystal arrays within a single cell during the color change. We demonstrate that reversible variations in crystal tilt within individual arrays are responsible for the light-induced color variations. These results settle a long-standing debate between the two proposed models, the "Venetian blinds" model and the "accordion" model. The insight gained from this biogenic light-induced photonic tunable system may provide inspiration for the design of artificial optical tunable systems. PMID:25914222

  11. Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

    PubMed

    Aydiner, Adnan; Sen, Fatma; Tambas, Makbule; Ciftci, Rumeysa; Eralp, Yesim; Saip, Pinar; Karanlik, Hasan; Fayda, Merdan; Kucucuk, Seden; Onder, Semen; Yavuz, Ekrem; Muslumanoglu, Mahmut; Igci, Abdullah

    2015-12-01

    Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required. PMID:26717372

  12. Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia.

    PubMed

    Floen, Miranda J; Forred, Benjamin J; Bloom, Elliot J; Vitiello, Peter F

    2014-10-01

    pathways were determined by utilizing a substrate trap (mass action trapping) proteomics approach. With this method, known Trx1 targets were detected, including peroxiredoxin-1as well as novel targets, including two HSP90 isoforms (HSP90AA1 and HSP90AB1). Reactive cysteines within the structure of HSP90 are known to modulate its ATPase-dependent chaperone activity through disulfide formation and S-nitrosylation. Whereas HSP90 expression is unchanged at the protein level during hyperoxic exposure, siRNA knockdown significantly increased hyperoxic cell death by 2.5-fold, indicating cellular dependence on HSP90 chaperone functions in response to hyperoxic exposure. These data support the hypothesis that hyperoxic impairment of Trx1 has a negative impact on HSP90-oxidative responses critical to cell survival, with potential implications for pathways implicated in lung development and the pathogenesis of BPD. PMID:25106706

  13. Thioredoxin-1 Redox Signaling Regulates Cell Survival in Response to Hyperoxia

    PubMed Central

    Floen, Miranda J.; Forred, Benjamin J.; Bloom, Elliot J.; Vitiello, Peter F.

    2014-01-01

    cytoprotection and cell survival pathways were determined by utilizing a substrate trap (mass action trapping) proteomics approach. With this method, known Trx1 targets were detected including peroxiredoxin-1 as well as novel targets, including two HSP90 isoforms (HSP90AA1 and HSP90AB1). Reactive cysteines within the structure of HSP90 are known to modulate its ATPase dependent chaperone activity through disulfide formation and S-nitrosylation. While HSP90 expression is unchanged at the protein level during hyperoxic exposure, siRNA knockdown significantly increased hyperoxic cell death by 2.5-fold, indicating cellular dependence on HSP90 chaperone functions in response of hyperoxic exposure. These data support the hypothesis that hyperoxic impairment of Trx1 negatively impacts HSP90-oxidative responses critical to cell survival with potential implications on pathways implicated in lung development and the pathogenesis of BPD. PMID:25106706

  14. Light-induced metastable defects or light-induced metastable H atoms in a-Si:H films?

    SciTech Connect

    Godet, C.

    1997-07-01

    In hydrogenated amorphous silicon (a-Si:H) films, the increase of the metastable defect density under high-intensity illumination is usually described by an empirical two-parameter stretched-exponential time dependence (characteristic time {tau}{sub SE} and dispersion parameter {beta}). In this study, a clearly different (one-parameter) analytic function is obtained from a microscopic model based on the formation of metastable H (MSH) atoms in a-Si:H films. Assuming that MSH atoms are the only mobile species, only three chemical reactions are significant: MSH are produced from doubly hydrogenated (SiH HSi) configurations and trapped either at broken bonds or Si-H bonds, corresponding respectively to light-induced annealing (LIA) and light-induced creation (LIC) of defects. Competition between trapping sites results in a saturation of N(t) at a steady-state value N{sub ss}. A one-parameter fit of this analytical function to experimental data is generally good, indicating that the use of a statistical distribution of trap energies is not necessary.

  15. Delayed neurotrophic treatment preserves nerve survival and electrophysiological responsiveness in neomycin-deafened guinea pigs.

    PubMed

    Yamagata, Takahiko; Miller, Josef M; Ulfendahl, Mats; Olivius, N Petri; Altschuler, Richard A; Pyykkö, Ilmari; Bredberg, Göran

    2004-10-01

    Benefits of cochlear prostheses for the deaf are dependent on survival and excitability of the auditory nerve. Degeneration of deafferented auditory nerve fibers is prevented and excitability maintained by immediate replacement therapy with exogenous neurotrophic factors, in vivo. It is important to know whether such interventions are effective after a delay following deafness, typical for the human situation. This study evaluated the efficacy of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor axokine-1 analogue (CNTF Ax1) application, 2 or 6 weeks postdeafening, in preventing further degeneration and a decrease in excitability. Guinea pigs were deafened and implanted with intracochlear stimulating electrodes, a scala tympani cannula-osmotic pump system, and auditory brainstem response (ABR) recording electrodes. Subjects received BDNF + CNTF Ax1 or artificial perilymph (AP) treatment for 27 days, beginning at 2 or 6 weeks following deafening. Electrical (E) ABR thresholds increased following deafening. After 1 week, in the 2-weeks-delayed neurotrophic factor treatment group, EABR thresholds decreased relative to AP controls, which were statistically significant at 2 weeks. In the 6-week delay group, a tendency to enhanced EABR sensitivity began at 2 weeks of treatment and increased thereafter, with a significant difference between neurotrophic factor- and AP-treated groups across the treatment period. A clear, statistically significant, enhanced survival of spiral ganglion cells was seen in both neurotrophic factor treatment groups relative to AP controls. These findings demonstrate that BDNF + CNTF Ax1 can act to delay or possibly even reverse degenerative and, likely apoptotic, processes well after they have been activated. These survival factors can rescue cells from death and enhance electrical excitability, even during the period of degeneration and cell loss when the spiral ganglion cell population is reduced by >50% (6 weeks). It is

  16. Is posttraumatic stress disorder an overlearned survival response? An evolutionary-learning hypothesis.

    PubMed

    Silove, D

    1998-01-01

    Contemporary learning theories of posttraumatic stress disorder (PTSD) provide an explanation for the phobic avoidant features but do not account fully for the intrusive phenomena that are so characteristic of the disorder. This article hypothesizes that a primitive learning center in the limbic system rehearses traumatic memories immediately following exposure to trauma, thus inducing durable memories of the sources of novel threat. It is postulated that the mechanism developed during early evolution when, in the absence of cognitive mechanisms, automatic learning following single exposure to novel threat would have conferred survival value on the species. With evolution of the brain, a second cortical pathway developed for the cognitive processing of trauma memories. It is possible that synchrony between the two phylogentically distinct pathways may be lost in vulnerable individuals under conditions of extreme stress resulting in failure of cortical inhibition of limbic trauma rehearsal mechanisms. A mismatch between archaic biological mechanisms and novel cues in the modern environment also may play a role in triggering traumatic memories and associated fight and flight reactions. The intrusive phenomena of PTSD thus may reflect an "overlearned survival response" in those in whom the putative limbic rehearsal mechanism evades cortical control. The heuristic value and limitations of such an evolutionary-learning theory are discussed. PMID:9706105

  17. Determinants of clinical response and survival in patients with congestive heart failure treated with captopril.

    PubMed

    Creager, M A; Faxon, D P; Halperin, J L; Melidossian, C D; McCabe, C H; Schick, E C; Ryan, T J

    1982-11-01

    The efficacy of chronic ambulatory captopril (CPT) therapy was evaluated over an 18-month period in 36 patients with refractory chronic congestive heart failure (CHF) by cardiac catheterization, treadmill exercise, nuclear scintigraphy, echocardiography, and symptomatology. Clinical improvement to New York Heart Association functional class I or class II was observed in 63% of the patients (20 of 32) after 2 months of treatment; this amelioration of CHF symptoms was sustained in 63% of the patients (10 of 16) at 18 months. Exercise tolerance increased in 64% of the patients (16 of 25) at early follow-up and in 79% (11 of 14) at late follow-up. Univariate analysis revealed that the pre- and post-CPT stroke work indices (SWI) and the post-CPT cardiac index related to favorable long-term clinical response. Fourteen CHF patients (39%) died during the 18-month follow-up. Univariate analysis revealed that the pretreatment SWI, right atrial pressure, plasma norepinephrine concentration, and echocardiographic shortening fraction were significant predictors of mortality. Multivariate analysis indicated that the SWI was the principal determinant of survival: the 18-month cumulative survival rate for CHF patients with a SWI less than 32 gm . m/m2 was 44% compared to 88% when the SWI was greater than 32 gm . m/m2. Thus, CPT results in sustained symptomatic and functional improvements in patients with advanced CHF, but the mortality remains high and is primarily related to the severity of cardiac dysfunction. PMID:6291360

  18. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  19. AKT activation controls cell survival in response to HDAC6 inhibition.

    PubMed

    Kaliszczak, M; Trousil, S; Ali, T; Aboagye, E O

    2016-01-01

    HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3'-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors. PMID:27362804

  20. Translation suppression promotes stress granule formation and cell survival in response to cold shock

    PubMed Central

    Hofmann, Sarah; Cherkasova, Valeria; Bankhead, Peter; Bukau, Bernd; Stoecklin, Georg

    2012-01-01

    Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2α (eIF2α) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock–induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2α phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia. PMID:22875991

  1. Thioredoxin-1 Increases Survival in Sepsis by Inflammatory Response Through Suppressing Endoplasmic Reticulum Stress.

    PubMed

    Chen, Guobing; Li, Xiang; Huang, Mengbing; Li, Mei; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2016-07-01

    Sepsis is the main cause of death in critically ill patients, pathogenesis of which is still unclear. The nuclear factor κB (NF-κB) inflammatory signal pathway mediated by endoplasmic reticulum stress is involved in sepsis. Thioredoxin-1 (Trx-1) is an important protein of regulating oxidative stress. It plays a crucial role in the anti-oxidation, anti-apoptosis, and anti-inflammation. However, the role and the mechanism of Trx-1 in sepsis have not been extensively studied. In the present study, we showed that the survival was longer in sepsis induced by cecal ligation and puncture in Trx-1 overexpression transgenic (Tg) mice compared with wild-type mice. Wet/dry lung weight ratio was decreased in Trx-1 Tg mice. The levels of TNF-α and IL-1β in plasma and lung tissue were inhibited in Tg mice. The expressions of glucose-regulated protein 78, inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2, C/EBP homologous protein, NF-κB, and inhibitors of NF-κBα were increased in lung tissue. More importantly, the overexpression of Trx-1 in transgenic mice suppressed NF-κB inflammatory signal pathway by inhibiting the activation of molecules involved in ER stress. Our results suggest that Trx-1 may play protective role in extending survival in sepsis by regulating inflammatory response through suppressing ER stress. PMID:27299588

  2. Light-induced metastability in pure and hydrogenated amorphous silicon

    NASA Astrophysics Data System (ADS)

    Queen, D. R.; Liu, X.; Karel, J.; Wang, Q.; Crandall, R. S.; Metcalf, T. H.; Hellman, F.

    2015-10-01

    Light soaking is found to increase the specific heat C and internal friction Q-1 of pure (a-Si) and hydrogenated (a-Si:H) amorphous silicon. At the lowest temperatures, the increases in C and Q-1 are consistent with an increased density of two-level systems (TLS). The light-induced increase in C persists to room temperature. Neither the sound velocity nor shear modulus change with light soaking indicating that the Debye specific heat is unchanged which suggests that light soaking creates localized vibrational modes in addition to TLS. The increase can be reversibly added and removed by light soaking and annealing, respectively, suggesting that it is related to the Staebler-Wronski effect (SWE), even in a-Si without H, and involves a reversible nanoscale structural rearrangement that is facilitated by, but does not require, H to occur.

  3. Light-induced chemical vapour deposition painting with titanium dioxide

    NASA Astrophysics Data System (ADS)

    Halary-Wagner, E.; Bret, T.; Hoffmann, P.

    2003-03-01

    Light-induced chemical vapour deposits of titanium dioxide are obtained from titanium tetra-isopropoxide (TTIP) in an oxygen and nitrogen atmosphere with a long pulse (250 ns) 308 nm XeCl excimer laser using a mask projection set-up. The demonstrated advantages of this technique are: (i) selective area deposition, (ii) precise control of the deposited thickness and (iii) low temperature deposition, enabling to use a wide range of substrates. A revolving mask system enables, in a single reactor load, to deposit shapes of controlled heights, which overlap to build up a complex pattern. Interferential multi-coloured deposits are achieved, and the process limitations (available colours and resolution) are discussed.

  4. Light-Induced Degradation of Thin Film Silicon Solar Cells

    NASA Astrophysics Data System (ADS)

    Hamelmann, F. U.; Weicht, J. A.; Behrens, G.

    2016-02-01

    Silicon-wafer based solar cells are still domination the market for photovoltaic energy conversion. However, most of the silicon is used only for mechanical stability, while only a small percentage of the material is needed for the light absorption. Thin film silicon technology reduces the material demand to just some hundred nanometer thickness. But even in a tandem stack (amorphous and microcrystalline silicon) the efficiencies are lower, and light-induced degradation is an important issue. The established standard tests for characterisation are not precise enough to predict the performance of thin film silicon solar cells under real conditions, since many factors do have an influence on the degradation. We will show some results of laboratory and outdoor measurements that we are going to use as a base for advanced modelling and simulation methods.

  5. Light-induced suppression of endogenous circadian amplitude in humans

    NASA Technical Reports Server (NTRS)

    Jewett, Megan; Czeisler, Charles A.; Kronauer, Richard E.

    1991-01-01

    A recent demonstration that the phase of the human circadian pacemaker could be inverted using an unconventional three-cycle stimulus has led to an investigation of whether critically timed exposure to a more moderate stimulus could drive that oscillator toward its singularity, a phaseless position at which the amplitude of circadian oscillation is zero. It is reported here that exposure of humans to fewer cycles of bright light, centered around the time at which the human circadian pacemaker is most sensitive to light-induced phase shifts, can markedly attenuate endogenous cicadian amplitude. In some cases this results in an apparent loss of rhythmicity, as expected to occur in the region of singularity.

  6. Polymer-Fullerene Network Formation via Light-Induced Crosslinking.

    PubMed

    Sugawara, Yuuki; Hiltebrandt, Kai; Blasco, Eva; Barner-Kowollik, Christopher

    2016-09-01

    A facile and efficient methodology for the formation of polymer-fullerene networks via a light-induced reaction is reported. The photochemical crosslinking is based on a nitrile imine-mediated tetrazole-ene cycloaddition reaction, which proceeds catalyst-free under UV-light irradiation (λmax = 320 nm) at ambient temperature. A tetrazole-functionalized polymer (Mn = 6500 g mol(-1) , Ð = 1.3) and fullerene C60 are employed for the formation of the hybrid networks. The tetrazole-functionalized polymer as well as the fullerene-containing networks are carefully characterized by NMR spectrometry, size exclusion chromatography, infrared spectroscopy, and elemental analysis. Furthermore, thermal analysis of the fullerene networks and their precursors is carried out. The current contribution thus induces an efficient platform technology for fullerene-based network formation. PMID:27336692

  7. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  8. The CovS/CovR acid response regulator is required for intracellular survival of group B Streptococcus in macrophages.

    PubMed

    Cumley, Nicola J; Smith, Leanne M; Anthony, Mark; May, Robin C

    2012-05-01

    Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome. PMID:22331428

  9. The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

    PubMed Central

    Cumley, Nicola J.; Smith, Leanne M.; Anthony, Mark

    2012-01-01

    Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome. PMID:22331428

  10. Survival and behavioral responses of larvae of the caddis fly Hydropsyche angustipennis to copper and diazinon

    SciTech Connect

    Geest, H.G. van der; Greve, G.D.; Haas, E.M. De; Scheper, B.B.; Kraak, M.H.S.; Stuijfzand, S.C.; Augustijn, K.H.; Admiraal, W.

    1999-09-01

    This study reports on newly developed short-term survival and behavioral tests with larvae of the caddis fly Hydropsyche angustipennis using two model toxicants, copper and diazinon. Mortality of first instar larvae was shown to be a reliable endpoint, and it was demonstrated that H. angustipennis is among the more sensitive aquatic insects in terms of both copper and diazinon. In addition, short-term behavioral responses were found to be indicative of adverse effects of ecologically relevant low doses of copper. Using the tests developed in this study, hydropsychid species are excellent tools for discerning the effects of individual toxicants present in large European rivers, and these species may help in defining the conditions for ecological rehabilitation.

  11. Ubiquitination by SAG regulates macrophage survival/death and immune response during infection

    PubMed Central

    Chang, S C; Ding, J L

    2014-01-01

    The checkpoint between the life and death of macrophages is crucial for the host's frontline immune defense during acute phase infection. However, the mechanism as to how the immune cell equilibrates between apoptosis and immune response is unclear. Using in vitro and ex vivo approaches, we showed that macrophage survival is synchronized by SAG (sensitive to apoptosis gene), which is a key member of the ubiquitin–proteasome system (UPS). When challenged by pathogen-associated molecular patterns (PAMPs), we observed a reciprocal expression profile of pro- and antiapoptotic factors in macrophages. However, SAG knockdown disrupted this balance. Further analysis revealed that ubiquitination of Bax and SARM (sterile α- and HEAT/armadillo-motif-containing protein) by SAG-UPS confers survival advantage to infected macrophages. SAG knockdown caused the accumulation of proapoptotic Bax and SARM, imbalance of Bcl-2/Bax in the mitochondria, induction of cytosolic cytochrome c and activation of caspase-9 and -3, all of which led to disequilibrium between life and death of macrophages. In contrast, SAG-overexpressing macrophages challenged with PAMPs exhibited upregulation of protumorigenic cytokines (IL-1β, IL-6 and TNF-α), and downregulation of antitumorigenic cytokine (IL-12p40) and anti-inflammatory cytokine (IL-10). This suggests that SAG-dependent UPS is a key switch between immune defense and apoptosis or immune overactivation and tumorigenesis. Altogether, our results indicate that SAG-UPS facilitates a timely and appropriate level of immune response, prompting future development of potential immunomodulators of SAG-UPS. PMID:24786833

  12. Survival Response to Increased Ceramide Involves Metabolic Adaptation through Novel Regulators of Glycolysis and Lipolysis

    PubMed Central

    Walls, Stanley M.; Singh, Alka; Zhu, Lihua Julie; Bamba, Takeshi; Fukusaki, Eiichiro; Srideshikan, Sargur M.; Harris, Greg L.; Ip, Y. Tony; Bodmer, Rolf; Acharya, Usha R.

    2013-01-01

    The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased

  13. Ubiquitination by SAG regulates macrophage survival/death and immune response during infection.

    PubMed

    Chang, S C; Ding, J L

    2014-09-01

    The checkpoint between the life and death of macrophages is crucial for the host's frontline immune defense during acute phase infection. However, the mechanism as to how the immune cell equilibrates between apoptosis and immune response is unclear. Using in vitro and ex vivo approaches, we showed that macrophage survival is synchronized by SAG (sensitive to apoptosis gene), which is a key member of the ubiquitin-proteasome system (UPS). When challenged by pathogen-associated molecular patterns (PAMPs), we observed a reciprocal expression profile of pro- and antiapoptotic factors in macrophages. However, SAG knockdown disrupted this balance. Further analysis revealed that ubiquitination of Bax and SARM (sterile α- and HEAT/armadillo-motif-containing protein) by SAG-UPS confers survival advantage to infected macrophages. SAG knockdown caused the accumulation of proapoptotic Bax and SARM, imbalance of Bcl-2/Bax in the mitochondria, induction of cytosolic cytochrome c and activation of caspase-9 and -3, all of which led to disequilibrium between life and death of macrophages. In contrast, SAG-overexpressing macrophages challenged with PAMPs exhibited upregulation of protumorigenic cytokines (IL-1β, IL-6 and TNF-α), and downregulation of antitumorigenic cytokine (IL-12p40) and anti-inflammatory cytokine (IL-10). This suggests that SAG-dependent UPS is a key switch between immune defense and apoptosis or immune overactivation and tumorigenesis. Altogether, our results indicate that SAG-UPS facilitates a timely and appropriate level of immune response, prompting future development of potential immunomodulators of SAG-UPS. PMID:24786833

  14. Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma.

    PubMed

    Shoushtari, A N; Landa, J; Kuk, D; Sanchez, A; Lala, B; Schmidt, N; Okoli, C; Chi, P; Dickson, M A; Gounder, M M; Keohan, M L; Crago, A M; Tap, W D; D'Angelo, S P

    2016-01-01

    Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy. Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1. Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) in N = 113 was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26-0.79, p = 0.005). Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites. PMID:27313489

  15. Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma

    PubMed Central

    Shoushtari, A. N.; Landa, J.; Kuk, D.; Sanchez, A.; Lala, B.; Schmidt, N.; Okoli, C.; Chi, P.; Dickson, M. A.; Gounder, M. M.; Keohan, M. L.; Crago, A. M.; Tap, W. D.; D'Angelo, S. P.

    2016-01-01

    Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy. Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1. Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) in N = 113 was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26–0.79, p = 0.005). Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites. PMID:27313489

  16. Immune response genes and pathogen presence predict migration survival in wild salmon smolts.

    PubMed

    Jeffries, Ken M; Hinch, Scott G; Gale, Marika Kirstin; Clark, Timothy D; Lotto, Andrew G; Casselman, Matthew T; Li, Shaorong; Rechisky, Erin L; Porter, Aswea D; Welch, David W; Miller, Kristina M

    2014-12-01

    We present the first data to link physiological responses and pathogen presence with subsequent fate during migration of wild salmonid smolts. We tagged and non-lethally sampled gill tissue from sockeye salmon (Oncorhynchus nerka) smolts as they left their nursery lake (Chilko Lake, BC, Canada) to compare gene expression profiles and freshwater pathogen loads with migration success over the first ~1150 km of their migration to the North Pacific Ocean using acoustic telemetry. Fifteen per cent of smolts were never detected again after release, and these fish had gene expression profiles consistent with an immune response to one or more viral pathogens compared with fish that survived their freshwater migration. Among the significantly upregulated genes of the fish that were never detected postrelease were MX (interferon-induced GTP-binding protein Mx) and STAT1 (signal transducer and activator of transcription 1-alpha/beta), which are characteristic of a type I interferon response to viral pathogens. The most commonly detected pathogen in the smolts leaving the nursery lake was infectious haematopoietic necrosis virus (IHNV). Collectively, these data show that some of the fish assumed to have died after leaving the nursery lake appeared to be responding to one or more viral pathogens and had elevated stress levels that could have contributed to some of the mortality shortly after release. We present the first evidence that changes in gene expression may be predictive of some of the freshwater migration mortality in wild salmonid smolts. PMID:25354752

  17. Laser Light Induced Photosensitization Of Lymphomas Cells And Normal Bone Marrow Cells

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.; Pervaiz, Shazib; Nealon, Don G.; VanderMeulen, David L.

    1988-06-01

    Dye mediated, laser light induced photosensitization was tested in an in vitro model for its efficacy in eliminating the contaminating tumor cells for ex vivo autologous bone marrow purging. Daudi and U-937 cells (3 x 106/ml) in RPMI-1640 supplemented with 0.25% human albumin were mixed with 20 µg/ml and 25 µg/ml of MC-540, respectively. These cell-dye mixtures were then exposed to 514 nm argon laser light. Identical treatment was given to the normal bone marrow cells. Viability was determined by the trypan blue exclusion method. Results show that at 31.2 J/cm2 irradiation, 99.9999% Daudi cells were killed while 87% of the normal bone marrow cells survived. No regrowth of Daudi cells was observed for 30 days in culture. However, a light dose of 93.6 J/cm2 was required to obtain 99.999% U-937 cell kill with 80% normal bone marrow cell survival. Mixing of irradiated bone marrow cells with an equal number of lymphoma cells did not interfere with the photodynamic killing of lymphoma cells. Exposure of cells to low doses of recombinant interferon-alpha prior to photodynamic therapy increased the viability of lymphoma cells.

  18. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers

    PubMed Central

    Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A.

    2015-01-01

    Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic

  19. Mitochondrial Cyclic AMP Response Element-binding Protein (CREB) Mediates Mitochondrial Gene Expression and Neuronal Survival*S

    PubMed Central

    Lee, Junghee; Kim, Chun-Hyung; Simon, David K.; Aminova, Lyaylya R.; Andreyev, Alexander Y.; Kushnareva, Yulia E.; Murphy, Anne N.; Lonze, Bonnie E.; Kim, Kwang-Soo; Ginty, David D.; Ferrante, Robert J.; Ryu, Hoon; Ratan, Rajiv R.

    2008-01-01

    Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders. PMID:16207717

  20. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy

    PubMed Central

    Rittig, Susanne M.; Haentschel, Maik; Weimer, Katrin J.; Heine, Annkristin; Müller, Martin R.; Brugger, Wolfram; Horger, Marius S.; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A.; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-01-01

    ABSTRACT Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003–2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0–3, 7–10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y.

  1. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-05-01

    Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y. PMID:27467913

  2. Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma

    PubMed Central

    Sun, Yongjian; Wu, Yi; Li, Weicheng; Kong, Zhen; Zou, Xiaoming

    2015-01-01

    We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma. PMID:26339355

  3. Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma.

    PubMed

    Sun, Yongjian; Wu, Yi; Li, Weicheng; Kong, Zhen; Zou, Xiaoming

    2015-01-01

    We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma. PMID:26339355

  4. Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease.

    PubMed

    Cohen, Camille; Royer, Bruno; Javaugue, Vincent; Szalat, Raphael; El Karoui, Khalil; Caulier, Alexis; Knebelmann, Bertrand; Jaccard, Arnaud; Chevret, Sylvie; Touchard, Guy; Fermand, Jean-Paul; Arnulf, Bertrand; Bridoux, Frank

    2015-11-01

    Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of plasma cell disorders, defined by linear Congo red-negative deposits of monoclonal light chain, heavy chain, or both along basement membranes. While renal involvement is prominent, treatment strategies, such as the impact of novel anti-myeloma agents, remain poorly defined. Here we retrospectively studied 49 patients with MIDD who received a median of 4.5 cycles of intravenous bortezomib plus dexamethasone. Of these, 25 received no additional treatment, 18 also received cyclophosphamide, while 6 also received thalidomide or lenalidomide. The hematological diagnoses identified 38 patients with monoclonal gammopathy of renal significance, 10 with symptomatic multiple myeloma, and 1 with Waldenstrom macroglobulinemia. The overall hematologic response rate, based on the difference between involved and uninvolved serum-free light chains (dFLCs), was 91%. After median follow-up of 54 months, 5 patients died and 10 had reached end-stage renal disease. Renal response was achieved in 26 patients, with a 35% increase in median eGFR and an 86% decrease in median 24-h proteinuria. Predictive factors were pre-treatment eGFR over 30 ml/min per 1.73 m(2) and post-treatment dFLC under 40 mg/l; the latter was the sole predictive factor of renal response by multivariable analysis. Thus, bortezomib-based therapy is a promising treatment strategy in MIDD, mainly when used early in the disease course. dFLC response is a favorable prognostic factor for renal survival. PMID:26176826

  5. Complement Peptide C3a Promotes Astrocyte Survival in Response to Ischemic Stress.

    PubMed

    Shinjyo, Noriko; de Pablo, Yolanda; Pekny, Milos; Pekna, Marcela

    2016-07-01

    Astrocytes are the most numerous cells in the central nervous system with a range of homeostatic and regulatory functions. Under normal conditions as well as after ischemia, astrocytes promote neuronal survival. We have previously reported that the complement-derived peptide C3a stimulates neuronal differentiation of neural progenitor cells and protects the immature brain tissue against hypoxic-ischemic injury. Here, we studied the effects of C3a on the response of mouse cortical astrocytes to ischemia. We have found that chemical ischemia, induced by combined inhibition of oxidative phosphorylation and glycolysis, upregulates the expression of C3a receptor in cultured primary astrocytes. C3a treatment protected wild-type but not C3a receptor-deficient astrocytes from cell death induced by chemical ischemia or oxygen-glucose deprivation by reducing ERK signaling and caspase-3 activation. C3a attenuated ischemia-induced upregulation of glial fibrillary acidic protein; however, the protective effects of C3a were not dependent on the presence of the astrocyte intermediate filament system. Pre-treatment of astrocytes with C3a during recovery abrogated the ischemia-induced neuroprotective phenotype of astrocytes. Jointly, these results provide the first evidence that the complement peptide C3a modulates the response of astrocytes to ischemia and increases their ability to cope with ischemic stress. PMID:25972241

  6. Effects of Alcohol on Tumor Growth, Metastasis, Immune Response, and Host Survival

    PubMed Central

    Meadows, Gary G.; Zhang, Hui

    2015-01-01

    Most research involving alcohol and cancer concerns the relationship between alcohol consumption and cancer risk and the mechanisms of carcinogenesis. This review relates the amount and duration of alcohol intake in humans and in animal models of cancer to tumor growth, angiogenesis, invasion, metastasis, immune response, and host survival in specific types and subtypes of cancer. Research on the influence of alcohol drinking on human cancer patients is limited. Although there is more information in animal models of cancer, many aspects still are ill defined. More research is needed to define the mechanisms that underlie the role of alcohol on cancer progression in both animals and humans. Activation of the immune system can play a positive role in keeping cancer under control, but this also can facilitate cancer progression. Additionally, a functional immune system is required for cancer patients to achieve an optimal response to conventional chemotherapy. Insight into the underlying mechanisms of these interactions could lead to effective immunotherapeutic approaches to treat alcoholics with cancer. Defining the epigenetic mechanisms that modulate cancer progression also has great potential for the development of new treatment options not only for treating alcoholics with cancer but also for treating other alcohol-induced diseases. PMID:26695753

  7. Effects of Alcohol on Tumor Growth, Metastasis, Immune Response, and Host Survival.

    PubMed

    Meadows, Gary G; Zhang, Hui

    2015-01-01

    Most research involving alcohol and cancer concerns the relationship between alcohol consumption and cancer risk and the mechanisms of carcinogenesis. This review relates the amount and duration of alcohol intake in humans and in animal models of cancer to tumor growth, angiogenesis, invasion, metastasis, immune response, and host survival in specific types and subtypes of cancer. Research on the influence of alcohol drinking on human cancer patients is limited. Although there is more information in animal models of cancer, many aspects still are ill defined. More research is needed to define the mechanisms that underlie the role of alcohol on cancer progression in both animals and humans. Activation of the immune system can play a positive role in keeping cancer under control, but this also can facilitate cancer progression. Additionally, a functional immune system is required for cancer patients to achieve an optimal response to conventional chemotherapy. Insight into the underlying mechanisms of these interactions could lead to effective immunotherapeutic approaches to treat alcoholics with cancer. Defining the epigenetic mechanisms that modulate cancer progression also has great potential for the development of new treatment options not only for treating alcoholics with cancer but also for treating other alcohol-induced diseases. PMID:26695753

  8. Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1

    PubMed Central

    Valdés, Pamela; Mercado, Gabriela; Vidal, Rene L.; Molina, Claudia; Parsons, Geoffrey; Court, Felipe A.; Martinez, Alexis; Galleguillos, Danny; Armentano, Donna; Schneider, Bernard L.; Hetz, Claudio

    2014-01-01

    Parkinson disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although growing evidence indicates that endoplasmic reticulum (ER) stress is a hallmark of PD, its exact contribution to the disease process is not well understood. Here we report that developmental ablation of X-Box binding protein 1 (XBP1) in the nervous system, a key regulator of the unfolded protein response (UPR), protects dopaminergic neurons against a PD-inducing neurotoxin. This survival effect was associated with a preconditioning condition that resulted from induction of an adaptive ER stress response in dopaminergic neurons of the SNpc, but not in other brain regions. In contrast, silencing XBP1 in adult animals triggered chronic ER stress and dopaminergic neuron degeneration. Supporting this finding, gene therapy to deliver an active form of XBP1 provided neuroprotection and reduced striatal denervation in animals injected with 6-hydroxydopamine. Our results reveal a physiological role of the UPR in the maintenance of protein homeostasis in dopaminergic neurons that may help explain the differential neuronal vulnerability observed in PD. PMID:24753614

  9. Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production

    PubMed Central

    Yang, Kun; Wu, Yongjian; Xie, Heping; Li, Miao; Ming, Siqi; Li, Liyan; Li, Meiyu; Wu, Minhao; Gong, Sitang; Huang, Xi

    2016-01-01

    Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. PMID:27251437

  10. Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production.

    PubMed

    Yang, Kun; Wu, Yongjian; Xie, Heping; Li, Miao; Ming, Siqi; Li, Liyan; Li, Meiyu; Wu, Minhao; Gong, Sitang; Huang, Xi

    2016-01-01

    Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. PMID:27251437

  11. Enhanced recovery of light-induced degradation on the micromorph solar cells by electric field

    NASA Astrophysics Data System (ADS)

    Sun, H.-C.; Yang, Y.-J.; Chen, J. Y.; Chao, T.-M.; Liu, C. W.; Lin, W.-Y.; Bi, C.-C.; Yeh, C.-H.

    2012-09-01

    The recovery of light-induced degradation of the tandem micromorph solar cell by applying reverse bias is compared with the single-junction amorphous silicon solar cell. The illuminated current density-voltage characteristics and external quantum efficiency show that the degradation of both the micromorph and the amorphous silicon cells can be recovered by applying sufficient reverse bias. The micromorph cell was recovered at smaller reverse bias than amorphous silicon cell. The abundant H in the microcrystalline silicon bottom cell of the micromorph cell can act as a reservoir to repair the defects in the amorphous silicon top cell at the reverse bias. This is responsible for small recovery bias of tandem cells.

  12. Photosynthetic Independence of Light-induced Anthocyanin Formation in Zea Seedlings 1

    PubMed Central

    Duke, Stephen O.; Fox, Sue B.; Naylor, Aubrey W.

    1976-01-01

    Results are reported which support the view that the photosynthetic photosystems are not involved in the high irradiance response (HIR) phenomenon of light-dependent anthocyanin biosynthesis in dark-grown Zea mays L. seedlings. A negative correlation between change in greening rates and change in light-dependent anthocyanin accumulation rates with age was demonstrated. Lack of chlorophyll synthesis in a strain of maize possessing a temperature-sensitive lesion for chlorophyll synthesis could not be correlated with light-induced anthocyanin accumulation. Furthermore, seedlings totally lacking photosynthetic capabilities, either due to a genetic lesion or to excision of all photosynthetic tissue, had an enhanced rate of photoinduced anthocyanin formation. This evidence indicates that the HIR results in the initiation of processes that are in competition with chloroplast development for substrate in normal, intact seedlings. PMID:16659449

  13. Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock

    PubMed Central

    Masubuchi, Satoru; Gao, Tianyan; O'Neill, Audrey; Eckel-Mahan, Kristin; Newton, Alexandra C.; Sassone-Corsi, Paolo

    2010-01-01

    The pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) differentially attenuates Akt, PKC, and ERK1/2 signaling, thereby controlling the duration and amplitude of responses evoked by these kinases. PHLPP1 is expressed in the mammalian central clock, the suprachiasmatic nucleus, where it oscillates in a circadian fashion. To explore the role of PHLPP1 in vivo, we have generated mice with a targeted deletion of the PHLPP1 gene. Here we show that PHLPP1-null mice, although displaying normal circadian rhythmicity, have a drastically impaired capacity to stabilize the circadian period after light-induced resetting, producing a large phase shift after light resetting. Our findings reveal that PHLPP1 exerts a previously unappreciated role in circadian control, governing the consolidation of circadian periodicity after resetting. PMID:20080691

  14. Light-Induced Temperature Transitions in Biodegradable Polymer and Nanorod Composites**

    PubMed Central

    Hribar, Kolin C.; Metter, Robert B.; Ifkovits, Jamie L.; Troxler, Thomas

    2010-01-01

    Shape-memory materials (including polymers, metals, and ceramics) are those that are processed into a temporary shape and respond to some external stimuli (e.g., temperature) to undergo a transition back to a permanent shape.[1, 2] Shape memory polymers are finding use in a range of applications from aerospace to fabrics, to biomedical devices and microsystem components.[3–5] For many applications, it would be beneficial to initiate heating with an external trigger (e.g., transdermal light exposure). In this work, we formulated composites of gold nanorods (<1% by volume) and biodegradable networks, where exposure to infrared light induced heating and consequently, shape transitions. The heating is repeatable and tunable based on nanorod concentration and light intensity and the nanorods did not alter the cytotoxicity or in vivo tissue response to the networks. PMID:19408258

  15. Functional Magnetic Resonance Imaging Response of Targeted Tumor Burden and Its Impact on Survival in Patients With Hepatocellular Carcinoma

    PubMed Central

    Corona-Villalobos, Celia Pamela; Halappa, Vivek Gowdra; Bonekamp, Susanne; Eng, John; Reyes, Diane; Cosgrove, David; Rastegar, Neda; Pan, Li; Pawlik, Timothy M.; Kamel, Ihab R.

    2015-01-01

    Purpose The aim of this study was to evaluate response of the targeted tumor burden by functional magnetic resonance imaging (MRI) including volumetric diffusion-weighted imaging and volumetric contrast-enhanced MRI (CE-MRI) and its impact on survival in patients with hepatocellular carcinoma treated with intra-arterial therapy (IAT). Materials and Methods This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study included 157 hepatocellular carcinoma lesions in 97 patients (78 men and 19 women; mean age, 64 years) treated with IAT. All patients had pretreatment and 3- to 4-week follow-up MRI with diffusion-weighted imaging and CE-MRI. All lesions 2 cm or larger that were targeted during the first session of IAT were segmented using research software (MR-Oncotreat) to determine targeted tumor burden relative to liver volume (%). Targeted tumor burden was stratified into low (≤10%) or high (>10%). Response using volumetric functional apparent diffusion coefficient (ADC; increase by ≥25%) and CE-MRI (decrease by ≥50% and ≥65% in arterial and venous enhancement [VE], respectively) was assessed in all targeted tumors (range, 1–11) using paired t tests. Kaplan-Meier survival analysis was performed and log-rank test was used to compare pairs of survival curves. Multivariate Cox regression analysis was performed to determine the simultaneous effect of treatment response and tumor burden on survival after adjusting for age, sex, and Child Pugh status. Results There was a significant increase in volumetric ADC (median, 15%; P < 0.001) and a decrease in volumetric arterial enhancement (AE) and VE (median AE, −43% and portal venous phase (PVP), −29%, respectively; P < 0.001) 3 to 4 weeks after treatment in the targeted tumor burden. Multivariable Cox regression demonstrated that both ADC response and low tumor burden were independently associated with greater survival (hazard ratios, 0.53 and 0

  16. Light-induced phosphorylation of a membrane protein plays an early role in signal transduction for phototropism in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Reymond, P.; Short, T. W.; Briggs, W. R.; Poff, K. L.

    1992-01-01

    Blue light is known to cause rapid phosphorylation of a membrane protein in etiolated seedlings of several plant species, a protein that, at least in etiolated pea seedlings and maize coleoptiles, has been shown to be associated with the plasma membrane. The light-driven phosphorylation has been proposed on the basis of correlative evidence to be an early step in the signal transduction chain for phototropism. In the Arabidopsis thaliana mutant JK224, the sensitivity to blue light for induction of first positive phototropism is known to be 20- to 30-fold lower than in wild type, whereas second positive curvature appears to be normal. While light-induced phosphorylation can be demonstrated in crude membrane preparations from shoots of the mutant, the level of phosphorylation is dramatically lower than in wild type, as is the sensitivity to blue light. Another A. thaliana mutant, JK218, that completely lacks any phototropic responses to up to 2 h of irradiation, shows a normal level of light-induced phosphorylation at saturation. Since its gravitropic sensitivity is normal, it is presumably blocked in some step between photoreception and the confluence of the signal transduction pathways for phototropism and gravitropism. We conclude from mutant JK224 that light-induced phosphorylation plays an early role in the signal transduction chain for phototropism in higher plants.

  17. Light-induced domain inversion with real-time diagnostics of the defect/domain wall interaction in lithium niobate

    NASA Astrophysics Data System (ADS)

    Sandmann, Christian; Dierolf, Volkmar

    2004-03-01

    Lithium niobate is a mature material which has widely been used in several applications, many of them exploiting the possibility to engineer domains in arbitrary shapes and patterns. Despite this technological driving force, the dramatic role of defects in the domain inversion (reflected e.g.: in a wide variation of coercive fields with stoichiometry) has not be clarified. To this end we will report two major breakthroughs enabling investigation of the dynamics of the domain wall/defect interaction. (1) light-induced domain inversion using visible laser in a confocal microscope, that allows us to directly "write" precise domain patterns, (2) real time observation of the changes occurring in the defect configuration of probe defect ions during domain inversion by probing defect luminescence. The latter can be used as a feedback for the light induced domain inversion. Moreover, we have a new tool to study the correlation between the rearrangement of defects and the occurrence of strain fields, as well as to investigate the origin of the light induced electric fields responsible for (1).

  18. Light-induced phosphorylation of a membrane protein plays an early role in signal transduction for phototropism in Arabidopsis thaliana.

    PubMed Central

    Reymond, P; Short, T W; Briggs, W R; Poff, K L

    1992-01-01

    Blue light is known to cause rapid phosphorylation of a membrane protein in etiolated seedlings of several plant species, a protein that, at least in etiolated pea seedlings and maize coleoptiles, has been shown to be associated with the plasma membrane. The light-driven phosphorylation has been proposed on the basis of correlative evidence to be an early step in the signal transduction chain for phototropism. In the Arabidopsis thaliana mutant JK224, the sensitivity to blue light for induction of first positive phototropism is known to be 20- to 30-fold lower than in wild type, whereas second positive curvature appears to be normal. While light-induced phosphorylation can be demonstrated in crude membrane preparations from shoots of the mutant, the level of phosphorylation is dramatically lower than in wild type, as is the sensitivity to blue light. Another A. thaliana mutant, JK218, that completely lacks any phototropic responses to up to 2 h of irradiation, shows a normal level of light-induced phosphorylation at saturation. Since its gravitropic sensitivity is normal, it is presumably blocked in some step between photoreception and the confluence of the signal transduction pathways for phototropism and gravitropism. We conclude from mutant JK224 that light-induced phosphorylation plays an early role in the signal transduction chain for phototropism in higher plants. Images PMID:11537679

  19. The Energetics of the Primary Proton Transfer in Bacteriorhodopsin Revisited: It is a Sequential Light Induced Charge Separation After All

    PubMed Central

    Braun-Sand, Sonja; Sharma, Pankaz K.; Chu, Zhen T.; Pisliakov, Andrei V.; Warshel, Arieh

    2008-01-01

    The light induced proton transport in bacteriorhodopsin has been considered as a model for other light-induced proton pumps. However, the exact nature of this process is still unclear. For example, it is not entirely clear what the driving force of the initial proton transfer is and, in particular, whether it reflects electrostatic forces or other effects. The present work simulates the primary proton transfer (PT) by a specialized combination of the EVB and the QCFF/PI methods. This combination allows us to obtain sufficient sampling and a quantitative free energy profile for the PT at different protein configurations. The calculated profiles provide new insight about energetics of the primary PT and its coupling to the protein conformational changes. The present finding confirms the tentative analysis of our early work [1] and determines that the overall PT process is driven by the energetics of the charge separation between the Schiff base and its counterion Asp85. Apparently, the light-induced relaxation of the steric energy of the chromophore leads to an increase in the ion-pair distance, and this drives the PT process. Our use of the linear response approximation allows us to estimate the change in the protein conformational energy and provides the first computational description of the coupling between the protein structural changes and the PT process. It is also found that the PT is not driven by twist-modulated changes of the Schiff base’s pKa, changes in the hydrogen bond directionality, or other non-electrostatic effects. Overall, based on a consistent use of structural information as the starting point for converging free-energy calculations, we conclude that the primary event should be described as a light-induced formation of an unstable ground state, whose relaxation leads to charge separation and to the destabilization of the ion-pair state. This provides the driving force for the subsequent PT steps. PMID:18387356

  20. Progranulin, a Major Secreted Protein of Mouse Adipose-Derived Stem Cells, Inhibits Light-Induced Retinal Degeneration

    PubMed Central

    Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru

    2014-01-01

    Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina. PMID:24233842

  1. Comparative analyses of light-induced anthocyanin accumulation and gene expression between the ray florets and leaves in chrysanthemum.

    PubMed

    Hong, Yan; Yang, Li-Wen; Li, Meng-Ling; Dai, Si-Lan

    2016-06-01

    Light is one of the key environmental factors that affect anthocyanin biosynthesis. However, the underlying molecular mechanism remains unclear, and many problems regarding phenotypic change and corresponding gene regulation have not been solved. In the present study, comparative analyses of light-induced anthocyanin accumulation and gene expression between the ray florets and leaves were performed in Chrysanthemum × morifolium 'Purple Reagan'. After contrasting the variations in the flower color phenotype and relative pigment content, as well as expression patterns of structural and regulator genes responsible for anthocyanin biosynthesis and photoreceptor between different plant organs under light and dark conditions, we concluded that (1) both the capitulum and foliage are key organs responding to light for chrysanthemum coloration; (2) compared with flavones, shading makes a greater decrease on the anthocyanins accumulation; (3) most of the structural and regulatory genes in the light-induced anthocyanin pathway specifically express in the ray florets; and (4) CmCHS, CmF3H, CmF3'H, CmANS, CmDFR, Cm3GT, CmMYB5-1, CmMYB6, CmMYB7-1, CmbHLH24, CmCOP1 and CmHY5 are key genes for light-induced anthocyanin biosynthesis in chrysanthemum ray florets, while on the transcriptional level, the expressions of CmPHYA, CmPHYB, CmCRY1a, CmCRY1b and CmCRY2 are insignificantly changed. Moreover, the inferred comprehensive effect of multiple signals on the accumulation of anthocyanins and transmission channel of light signal that exist between the leaves and ray florets were further discussed. These results further our understanding of the relationship between the gene expression and light-induced anthocyanin biosynthesis, and lay foundations for the promotion of the molecular breeding of novel flower colors in chrysanthemums. PMID:26990403

  2. Different role of the Jalpha helix in the light-induced activation of the LOV2 domains in various phototropins.

    PubMed

    Koyama, Takayuki; Iwata, Tatsuya; Yamamoto, Atsushi; Sato, Yoshiaki; Matsuoka, Daisuke; Tokutomi, Satoru; Kandori, Hideki

    2009-08-18

    Phototropins (phot) are blue light receptors in plants which are involved in phototropism, stomatal opening, and chloroplast movements. Phototropin has two LOV domains (LOV1 and LOV2), and the LOV2 domain is responsible for activation of Ser/Thr kinase. There is an alpha-helix at the C-terminal side of the LOV2 domain, which is called the Jalpha helix. The functional importance of the Jalpha helix has been established for Arabidopsis phot1, where light-induced structural perturbation takes place in the Jalpha helix during the photocycle of LOV2 domains. However, the present FTIR study reports a different role of the Jalpha helix in light-induced signal transduction of LOV2 domains. Here we construct LOV2 domains with (LOV-Jalpha) and without (LOV-core) the Jalpha helix for Arabidopsis phot1 and phot2 and Adiantum neochrome 1 and compare their light-induced difference FTIR spectra. Light-induced protein structural changes differ significantly between LOV-Jalpha and LOV-core for Arabidopsis phot1 [Yamamoto, A., Iwata, T., Sato, Y., Matsuoka, D., Tokutomi, S., and Kandori, H. (2009) Biophys. J. 96, 2771-2778]. In contrast, the difference spectra are identical between LOV-Jalpha and LOV-core for Adiantum neochrome 1. In Arabidopsis phot2, the protein structural changes are intermediate between Arabidopsis phot1 and Adiantum neochrome 1. These results suggest that the conformational changes of the Jalpha helix and the interaction between the LOV-core and the Jalpha helix are different among phototropins. The role of the Jalpha helix for signal transduction in phototropins is discussed. PMID:19601589

  3. Hydrogen peroxide generated by NADPH oxidase is involved in high blue-light-induced chloroplast avoidance movements in Arabidopsis

    NASA Astrophysics Data System (ADS)

    Wen, Feng; Xing, Da; Zhang, Lingrui

    2009-08-01

    One of the most important functions of blue light is to induce chloroplast movements by reducing the damage to photosynthetic machinery under excess light. Hydrogen peroxide (H2O2), generated by various environmental stimuli, can act as a signaling molecule that regulates a number of developmental processes and environmental responses. To investigate whether H2O2 is involved in high blue light-induced chloroplast avoidance movements, we use luminescence spectrometer to observe H2O2 generation with the assistance of the fluorescence probe dichlorofluorescin diacetate (H2DCF-DA). After treatment with high blue light, a large quantity of H2O2 indicated by the fluorescence intensity of DCF is produced in a dose-dependent manner in leaf strip of Arabidopsis. Enzymatic assay shows that the activity of NADPH oxidase, which is a major site for H2O2 generation, also rapidly increases in treated strips. Exogenously applied H2O2 can promote the high blue light-induced chloroplast movements. Moreover, high blue light-induced H2O2 generation can be abolished completely by addition of exogenous catalase (CAT), and partly by diphenylene iodonium (DPI) and dichlorophenyl dimethylurea (DCMU), which are an NADPH oxidase inhibitor and a blocker of electron transport chain. And subsequent chloroplast movements can be abolished by CAT and DPI, but not by DCMU. These results presented here suggested that high blue light can induce oxidative burst, and NADPH oxidase as a major producer for H2O2 is involved in blue light-induced chloroplast avoidance movements.

  4. Retino-hypothalamic regulation of light-induced murine sleep

    PubMed Central

    Muindi, Fanuel; Zeitzer, Jamie M.; Heller, Horace Craig

    2014-01-01

    The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages. PMID:25140132

  5. Light-induced self-assembly of active rectification devices

    PubMed Central

    Stenhammar, Joakim; Wittkowski, Raphael; Marenduzzo, Davide; Cates, Michael E.

    2016-01-01

    Self-propelled colloidal objects, such as motile bacteria or synthetic microswimmers, have microscopically irreversible individual dynamics—a feature they share with all living systems. The incoherent behavior of individual swimmers can be harnessed (or “rectified”) by microfluidic devices that create systematic motions that are impossible in equilibrium. We present a computational proof-of-concept study showing that such active rectification devices could be created directly from an unstructured “primordial soup” of light-controlled motile particles, solely by using spatially modulated illumination to control their local propulsion speed. Alongside both microscopic irreversibility and speed modulation, our mechanism requires spatial symmetry breaking, such as a chevron light pattern, and strong interactions between particles, such as volume exclusion, which cause a collisional slowdown at high density. Together, we show how these four factors create a novel, many-body rectification mechanism. Our work suggests that standard spatial light modulator technology might allow the programmable, light-induced self-assembly of active rectification devices from an unstructured particle bath. PMID:27051883

  6. Diagnosis of dental caries using quantitative light-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Amaechi, Bennett T.; Higham, Susan M.

    2001-10-01

    Current dental diagnostic methods can detect caries but cannot quantify the mineral status of the lesion. Quantitative Light-induced Fluorescence (QLF) measures the percentage fluorescence radiance change of demineralised enamel with respect to surround sound enamel, and related it directly to the amount of mineral lost during demineralisation. Demineralisation of teeth to produce caries-like lesions and the subsequent remineralisation of the lesions were monitored quantitatively and longitudinally with QLF. The influence of factors such as presence of plaque or saliva, lesion staining, lesion magnification, tooth thickness and developmental hypomineralisation, on the reproducibility of QLF imaging and analysis were investigated, Results showed that the integrated fluorescence change (hence the mineral loss) increased linearly with demineralisation time and decreased with increasing remineralisation time. Caries detection was limited by saliva or plaque, but enhanced by staining. QLF could not discriminate between developmental hypomineralisation and caries. Neither the variation in tooth thickness nor lesion magnification within the limit of a sharp image made a significant difference in QLF analysis. It was concluded that QLF could detect and quantitatively monitor the mineral changes in an incipient caries on a longitudinal basis, however detection may be limited by the presence of saliva or plaque or enhanced by staining.

  7. Light induced DEP for immobilizing and orienting Escherichia coli bacteria

    NASA Astrophysics Data System (ADS)

    Miccio, Lisa; Marchesano, Valentina; Mugnano, Martina; Grilli, Simonetta; Ferraro, Pietro

    2016-01-01

    Manipulating bacteria and understanding their behavior when interacting with different substrates are of fundamental importance for patterning, detection, and any other topics related to health-care, food-enterprise, etc. Here, we adopt an innovative dielectrophoretic (DEP) approach based on electrode-free DEP for investigating smart but simple strategies for immobilization and orientation of bacteria. Escherichia coli DH5-alpha strain has been selected as subject of the study. The light induced DEP is achieved through ferroelectric iron-doped lithium niobate crystals used as substrates. Due to the photorefractive (PR) property of such material, suitable light patterns allow writing spatial-charges-distribution inside its volume and the resultant electric fields are able to immobilize E. coli on the surface. The experiments showed that, after laser irradiation, about 80% of bacteria is blocked and oriented along a particular direction on the crystals within an area of few square centimeters. The investigation presented here could open the way for detection or patterning applications based on a new driving mechanism. Future perspectives also include the possibility to actively switch by light the DEP forces, through the writing/erasing characteristic of PR fields, to dynamically control biofilm spatial structure and arrangement.

  8. Light-induced self-assembly of active rectification devices.

    PubMed

    Stenhammar, Joakim; Wittkowski, Raphael; Marenduzzo, Davide; Cates, Michael E

    2016-04-01

    Self-propelled colloidal objects, such as motile bacteria or synthetic microswimmers, have microscopically irreversible individual dynamics-a feature they share with all living systems. The incoherent behavior of individual swimmers can be harnessed (or "rectified") by microfluidic devices that create systematic motions that are impossible in equilibrium. We present a computational proof-of-concept study showing that such active rectification devices could be created directly from an unstructured "primordial soup" of light-controlled motile particles, solely by using spatially modulated illumination to control their local propulsion speed. Alongside both microscopic irreversibility and speed modulation, our mechanism requires spatial symmetry breaking, such as a chevron light pattern, and strong interactions between particles, such as volume exclusion, which cause a collisional slowdown at high density. Together, we show how these four factors create a novel, many-body rectification mechanism. Our work suggests that standard spatial light modulator technology might allow the programmable, light-induced self-assembly of active rectification devices from an unstructured particle bath. PMID:27051883

  9. Early light-induced proteins protect Arabidopsis from photooxidative stress.

    PubMed

    Hutin, Claire; Nussaume, Laurent; Moise, Nicolae; Moya, Ismaël; Kloppstech, Klaus; Havaux, Michel

    2003-04-15

    The early light-induced proteins (ELIPs) belong to the multigenic family of light-harvesting complexes, which bind chlorophyll and absorb solar energy in green plants. ELIPs accumulate transiently in plants exposed to high light intensities. By using an Arabidopsis thaliana mutant (chaos) affected in the posttranslational targeting of light-harvesting complex-type proteins to the thylakoids, we succeeded in suppressing the rapid accumulation of ELIPs during high-light stress, resulting in leaf bleaching and extensive photooxidative damage. Constitutive expression of ELIP genes in chaos before light stress resulted in ELIP accumulation and restored the phototolerance of the plants to the wild-type level. Free chlorophyll, a generator of singlet oxygen in the light, was detected by chlorophyll fluorescence lifetime measurements in chaos leaves before the symptoms of oxidative stress appeared. Our findings indicate that ELIPs fulfill a photoprotective function that could involve either the binding of chlorophylls released during turnover of pigment-binding proteins or the stabilization of the proper assembly of those proteins during high-light stress. PMID:12676998

  10. Light-induced Ca2+ release in the visible cones of the zebrafish.

    PubMed

    Cilluffo, Marianne C; Matthews, Hugh R; Brockerhoff, Susan E; Fain, Gordon L

    2004-01-01

    We used suction-pipette recording and fluo-4 fluorescence to study light-induced Ca2+ release from the visible double cones of zebrafish. In Ringer, light produces a slow decrease in fluorescence which can be fitted by the sum of two decaying exponentials with time constants of 0.5 and 3.8 s. In 0Ca2+-0Na+ solution, for which fluxes of Ca2+ across the outer segment plasma membrane are greatly reduced, light produces a slow increase in fluorescence. Both the decrease and increase are delayed after incorporation of the Ca2+ chelator BAPTA, indicating that both are produced by a change in Ca2+. If the Ca2+ pool is first released by bright light in 0Ca2+-0Na+ solution and the cone returned to Ringer, the time course of Ca2+ decline is much faster than in Ringer without previous light exposure. This indicates that the time constants of 0.5 and 3.8 s actually reflect a sum of Na+/Ca2+-K+ exchange and light-induced release of Ca2+. The Ca2+ released by light appears to come from at least two sites, the first comprising 66% of the total pool and half-released by bleaching 4.8% of the pigment. Release of the remaining Ca2+ from the second site requires the bleaching of nearly all of the pigment. If, after release, the cone is maintained in darkness, a substantial fraction of the Ca2+ returns to the release pool even in the absence of pigment regeneration. The light-induced release of Ca2+ can produce a modulation of the dark current as large as 0.75 pA independently of the normal transduction cascade, though the rise time of the current is considerably slower than the normal light response. These experiments show that Ca2+ can be released within the cone outer segment by light intensities within the physiological range of photopic vision. The role this Ca2+ release plays remains unresolved. PMID:15579223

  11. Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage.

    PubMed

    Mattheij, Nadine J A; Braun, Attila; van Kruchten, Roger; Castoldi, Elisabetta; Pircher, Joachim; Baaten, Constance C F M J; Wülling, Manuela; Kuijpers, Marijke J E; Köhler, Ralf; Poole, Alastair W; Schreiber, Rainer; Vortkamp, Andrea; Collins, Peter W; Nieswandt, Bernhard; Kunzelmann, Karl; Cosemans, Judith M E M; Heemskerk, Johan W M

    2016-02-01

    Scott syndrome is a rare bleeding disorder, characterized by altered Ca(2+)-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano)6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6 min (control 6.4 min, P < 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (-65 to 90%); 2) lowered Ca(2+)-dependent swelling (-80%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome. PMID:26481309

  12. Oosorption in response to poor food: complexity in the trade-off between reproduction and survival.

    PubMed

    Moore, Patricia J; Attisano, Alfredo

    2011-09-01

    Plasticity in reproductive physiology is one avenue by which environmental signals, such as poor quality food, can be coordinated with adaptive responses. Insects have the ability to resorb oocytes that are not oviposited. Oosorption is proposed to be an adaptive mechanism to optimize fitness in hostile environments, recouping resources that might otherwise be lost, and reinvesting them into future reproductive potential. We tested the hypothesis that oosorption is an evolved mechanism by which females can reallocate resources from current reproductive effort to survival and future reproduction, when conditions for reproduction are poor, by examining the reproductive physiology and life-history outcome under poor quality food in populations of the milkweed bug (Oncopeltus fasciatus) that have adapted to live on sunflower seed. Females fed a diet of pumpkin seeds, known to be a poor host food, had higher levels of ovarian apoptosis (oosorption), lower reproductive output, but no reduction in life span under poor nutrition, as predicted under the oosorption hypothesis. However, the schedule of reproduction was surprising given the "wait to reproduce" assumption of oosorption as early fecundity was unaffected. PMID:22393481

  13. Oosorption in response to poor food: complexity in the trade-off between reproduction and survival

    PubMed Central

    Moore, Patricia J; Attisano, Alfredo

    2011-01-01

    Plasticity in reproductive physiology is one avenue by which environmental signals, such as poor quality food, can be coordinated with adaptive responses. Insects have the ability to resorb oocytes that are not oviposited. Oosorption is proposed to be an adaptive mechanism to optimize fitness in hostile environments, recouping resources that might otherwise be lost, and reinvesting them into future reproductive potential. We tested the hypothesis that oosorption is an evolved mechanism by which females can reallocate resources from current reproductive effort to survival and future reproduction, when conditions for reproduction are poor, by examining the reproductive physiology and life-history outcome under poor quality food in populations of the milkweed bug (Oncopeltus fasciatus) that have adapted to live on sunflower seed. Females fed a diet of pumpkin seeds, known to be a poor host food, had higher levels of ovarian apoptosis (oosorption), lower reproductive output, but no reduction in life span under poor nutrition, as predicted under the oosorption hypothesis. However, the schedule of reproduction was surprising given the “wait to reproduce” assumption of oosorption as early fecundity was unaffected. PMID:22393481

  14. Root based responses account for Psidium guajava survival at high nickel concentration.

    PubMed

    Bazihizina, Nadia; Redwan, Mirvat; Taiti, Cosimo; Giordano, Cristiana; Monetti, Emanuela; Masi, Elisa; Azzarello, Elisa; Mancuso, Stefano

    2015-02-01

    The presence of Psidium guajava in polluted environments has been reported in recent studies, suggesting that this species has a high tolerance to the metal stress. The present study aims at a physiological characterization of P. guajava response to high nickel (Ni) concentrations in the root-zone. Three hydroponic experiments were carried out to characterize the effects of toxic Ni concentrations on morphological and physiological parameters of P. guajava, focusing on Ni-induced damages at the root-level and root ion fluxes. With up to 300μM NiSO4 in the root-zone, plant growth was similar to that in control plants, whereas at concentrations higher than 1000μM NiSO4 there was a progressive decline in plant growth and leaf gas exchange parameters; this occurred despite, at all considered concentrations, plants limited Ni(2+) translocation to the shoot, therefore avoiding shoot Ni(2+) toxicity symptoms. Maintenance of plant growth with 300μM Ni(2+) was associated with the ability to retain K(+) in the roots meanwhile 1000 and 3000μM NiSO4 led to substantial K(+) losses. In this study, root responses mirror all plant performances suggesting a direct link between root functionality and Ni(2+) tolerance mechanisms and plant survival. Considering that Ni was mainly accumulated in the root system, the potential use of P. guajava for Ni(2+) phytoextraction in metal-polluted soils is limited; nevertheless, the observed physiological changes indicate a good Ni(2+) tolerance up to 300μM NiSO4 suggesting a potential role for the phytostabilization of polluted soils. PMID:25462976

  15. Theory of light-induced deformation of azobenzene elastomers: Influence of network structure

    NASA Astrophysics Data System (ADS)

    Toshchevikov, V. P.; Saphiannikova, M.; Heinrich, G.

    2012-07-01

    Azobenzene elastomers have been extensively explored in the last decade as photo-deformable smart materials which are able to transform light energy into mechanical stress. Presently, there is a great need for theoretical approaches to accurately predict the quantitative response of these materials based on their microscopic structure. Recently, we proposed a theory of light-induced deformation of azobenzene elastomers using a simple regular cubic network model [V. Toshchevikov, M. Saphiannikova, and G. Heinrich, J. Phys. Chem. B 116, 913 (2012), 10.1021/jp206323h]. In the present study, we extend the previous theory using more realistic network models which take into account the random orientation of end-to-end vectors of network strands as well as the molecular weight distribution of the strands. Interaction of the chromophores with the linearly polarized light is described by an effective orientation potential which orients the chromophores perpendicular to the polarization direction. We show that both monodisperse and polydisperse azobenzene elastomers can demonstrate either a uniaxial expansion or contraction along the polarization direction. The sign of deformation (expansion/contraction) depends on the orientation distribution of chromophores with respect to the main chains which is defined by the chemical structure and by the lengths of spacers. The degree of cross-linking and the polydispersity of network strands do not affect the sign of deformation but influence the magnitude of light-induced deformation. We demonstrate that photo-mechanical properties of mono- and poly-disperse azobenzene elastomers with random spatial distribution of network strands can be described in a very good approximation by a regular cubic network model with an appropriately chosen length of the strands.

  16. Rapamycin attenuates visible light-induced injury in retinal photoreceptor cells via inhibiting endoplasmic reticulum stress.

    PubMed

    Li, Guang-Yu; Fan, Bin; Jiao, Ying-Ying

    2014-05-14

    An extended exposure of the retina to visible light may lead to photochemical damage in retinal photoreceptor cells. The exact mechanism of retinal light damage remains unknown, and an effective therapy is still unavailable. Here, we demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), markedly protected 661W photoreceptor cells from visible light exposure-induced damage at the nanomolar level. We also observed by transmission electron microscopy that light exposure led to severe endoplasmic reticulum (ER) stress in 661W cells as well as abnormal endomembranes and ER membranes. In addition, obvious upregulated ER stress markers were monitored by western blot at the protein level and by quantitative reverse transcription-polymerase chain reaction (RT-PCR) at the mRNA level. Interestingly, rapamycin pretreatment significantly suppressed light-induced ER stress and all three major branches of the unfolded protein response (UPR), including the RNA-dependent protein kinase-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) pathways both at the protein and mRNA levels. Additionally, the inhibition of ER stress by rapamycin was further confirmed with a dithiothreitol (DTT; a classical ER stress inducer)-damaged 661W cell model. Meanwhile, our results also revealed that rapamycin was able to remarkably inhibit the activation of mTOR and its downstream factors eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), p-4EBP1, p70, p-p70, and phosphorylated ribosomal protein S6 kinase (p-S6K) in the light-injured 661W cells. Thus, these data indicate that visible light induces ER stress in 661W cells; whereas the mTOR inhibitor, rapamycin, effectively protects 661W cells from light injury through suppressing the ER stress pathway. PMID:24607296

  17. Light-Induced Reversible Change of Roughness and Thickness of Photosensitive Polymer Brushes.

    PubMed

    Kopyshev, Alexey; Galvin, Casey J; Patil, Rohan R; Genzer, Jan; Lomadze, Nino; Feldmann, David; Zakrevski, Juri; Santer, Svetlana

    2016-07-27

    We investigate light-induced changes in thickness and roughness of photosensitive polymer brushes containing azobenzene cationic surfactants by atomic force microscopy (AFM) in real time during light irradiation. Because the cis-state of azobenzene unit requires more free volume than its trans counterpart, the UV light-induced expansion of polymer thin films associated with the trans-to-cis isomerism of azobenzene groups is expected to occur. This phenomenon is well documented in physisorbed polymer films containing azobenzene groups. In contrast, photosensitive polymer brushes show a decrease in thickness under UV irradiation. We have found that the azobenzene surfactants in their trans-state form aggregates within the brush. Under irradiation, the surfactants undergo photoisomerization to the cis-state, which is more hydrophilic. As a consequence, the aggregates within the brush are disrupted, and the polymer brush contracts. When subsequently irradiated with blue light the polymer brush thickness returns back to its initial value. This behavior is related to isomerization of the surfactant to the more hydrophobic trans-state and subsequent formation of surfactant aggregates within the polymer brush. The photomechanical function of the dry polymer brush, i.e., contraction and expansion, was found to be reversible with repeated irradiation cycles and requires only a few seconds for switching. In addition to the thickness change, the roughness of the brush also changes reversibly between a few Angstroms (blue light) and several nanometers (UV light). Photosensitive polymer brushes represent smart films with light responsive thickness and roughness that could be used for generating dynamic fluctuating surfaces, the function of which can be turned on and off in a controllable manner on a nanometer length scale. PMID:27351592

  18. Will Capitalism Survive? A Challenge by Paul Johnson with Twelve Responses.

    ERIC Educational Resources Information Center

    Lefever, Ernest W., Ed.

    A challenge on the survival of capitalism and its future is set forth in this document. Although industrial capitalism is strong, five dangers that threaten its survival are cited: (1) the collectivist bias of Western intellectuals; (2) the influence of the ecological apocalyptics; (3) the assault on the market by big government; (4) the…

  19. All or nothing: Survival, reproduction and oxidative balance in Spotted Wing Drosophila (Drosophila suzukii) in response to cold.

    PubMed

    Plantamp, Christophe; Salort, Katleen; Gibert, Patricia; Dumet, Adeline; Mialdea, Gladys; Mondy, Nathalie; Voituron, Yann

    2016-06-01

    Winter severity and overwintering capacity are key ecological factors in successful invasions, especially in ectotherms. The integration of physiological approaches into the study of invasion processes is emerging and promising. Physiological information describes the mechanisms underlying observed survival and reproductive capacities, and it can be used to predict an organism's response to environmental perturbations such as cold temperatures. We investigated the effects of various cold treatments on life history and physiological traits of an invasive pest species, Drosophila suzukii, such as survival, fertility and oxidative balance. This species, a native of temperate Asian areas, is known to survive where cold temperatures are particularly harsh and has been recently introduced into Europe and North America. We found that cold treatments had a strong impact on adult survival but no effect on female's fertility. Although only minor changes were observed after cold treatment on studied physiological traits, a strong sex-based difference was observed in both survival and physiological markers (antioxidant defences and oxidative markers). Females exhibited higher survival, reduced oxidative defences, less damage to nucleic acids, and more damage to lipids. These results suggest that D. suzukii relies on a pathway other than oxidative balance to resist cold injury. Altogether, our results provide information concerning the mechanisms of successful invasion by D. suzukii. These findings may assist in the development of population models that predict the current and future geographic ranges of this species. PMID:27040270

  20. Controllable 3D alginate hydrogel patterning via visible-light induced electrodeposition.

    PubMed

    Dai, Gaole; Wan, Wenfeng; Zhao, Yuliang; Wang, Zixun; Li, Wenjun; Shi, Peng; Shen, Yajing

    2016-01-01

    The fabrication of alginate hydrogel in 3D has recently received increasing attention owing to its distinct efficacy as biocompatible scaffold for 3D cell culture, biomedical and tissue engineering. We report a controllable 3D alginate hydrogel patterning method by developing a visible-light induced electrodeposition chip. The chip mainly consists of a photoconductive titanyl phthalocyanine (TiOPc) anode plate, an indium tin oxide (ITO) cathode plate and the mixed solution (1% sodium alginate and 0.25% CaCO3 nano particles) between them. After a designed visible-light pattern is projected onto the TiOPc plate, the produced H(+) by electrolysis will trigger Ca(2+) near the anode (illuminated area), and then the gelation of calcium alginate patterns, as desired, happens controllably. In addition, we further establish an exponential model to elucidate the gel growth v.s. time and current density. The results indicate that the proposed method is able to fabricate various 3D alginate hydrogel patterns in a well controllable manner, and maintain the laden cells at high survival rate (>98% right after gel formation). This research paves an alternative way for 3D alginate hydrogel patterning with high controllability and productivity, which would benefit the research in biomedical and tissue engineering. PMID:27108617

  1. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  2. Light-induced metastable states in ferroelectric oxides

    NASA Astrophysics Data System (ADS)

    Liu, G. K.; Vikhnin, V. S.; Kapphan, S. E.

    2007-07-01

    New Raman scattering lines (at 463 cm-1 and at 156 cm-1) induced by strong enough optical pumping in nominally pure KTaO3 crystals are manifested. The model of such effect is proposed. This model is based on the light-induced formation of metastable polar clusters constructed from bi-polaronic excitons - Charge Transfer Vibronic Excitons (CTVEs) with their high degree alignment. The CTVEs are caused by photo-carriers with high local concentration which are trapped to local potential wells related with long-range defect fields. CTVE formation are realized in these potential wells due to significant easing of charge transfer fluctuations induced by photo-carrier screening effects. This model is effective also for explanation of giant dielectric constant inducing by strong illumination which was detected recently in KTaO3 and SrTiO3 by Japanese investigators [M. Takesada, T. Yagi, M. Itoh, S. Koshihara, J. Phys. Soc. Jpn. 72 (2003) 37; T. Hasegawa, S. Mouri, Y. Yamada, K. Tanaka, J. Phys. Soc. Jpn. 72 (2003) 41; I. Katayama, Y. Ichikawa, K. Tanaka, Phys. Rev. B 67 (2003) 100102(R)]. Another aspect of the present study was specific recombination luminescence of CTVEs which was investigated here with respect to the influence of additional IR pumping. The present investigation has led to experimental evidence of new, mainly non-linear CTVE with good defined metastable behavior. Such an essentially anharmonic CTVE with respect to charge transfer and lattice displacements was predicted recently in our work [V.S. Vikhnin, Solid State Commun. 127 (2003) 283]. Here, we present experimental evidence of the existence of a new type of exciton state.

  3. Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

    PubMed Central

    Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Chan, Landon L.; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

    2014-01-01

    Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

  4. Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-{kappa}B pathway

    SciTech Connect

    Jin, Hong Ri; Jin, Xuejun; Lee, Jung Joon

    2010-10-01

    Research highlights: {yields} LIGHT induces ZFP91expression and nuclear translocation of p65, p52, and RelB in LT{beta}R signaling. {yields} ZFP91 knock-down abolishes DNA-binding activity of p52 and RelB but not of p65. {yields} ZFP91 regulates LIGHT-induced stabilization and activation of NIK. {yields} ZFP91 is required for the expression of non-canonical NF-{kappa}B target genes. -- Abstract: LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its function is mediated through lymphotoxin-{beta} receptor (LT{beta}R), which is known to play important roles in inflammatory and immune responses through activation of NF-{kappa}B signaling pathways. However, molecular mechanism of LT{beta}R ligation-induced NF-{kappa}B signaling remains incompletely understood. In this report we demonstrate that a novel zinc-finger protein 91 (ZFP91) is a critical regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. ZFP91 appears to be required for NF-{kappa}B2 (p100) processing to p52, nuclear translocation of p52 and RelB, and DNA-binding activity of NF-{kappa}B in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. Furthermore, ZFP91 knock-down by RNA interference blocks the LIGHT-induced accumulation of NIK and p100 processing, as well as the expression of non-canonical NF-{kappa}B target genes. These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway in LT{beta}R signaling.

  5. Autophagy in response to photodynamic therapy: cell survival vs. cell death

    NASA Astrophysics Data System (ADS)

    Oleinick, Nancy L.; Xue, Liang-yan; Chiu, Song-mao; Joseph, Sheeba

    2009-02-01

    Autophagy (or more properly, macroautophagy) is a pathway whereby damaged organelles or other cell components are encased in a double membrane, the autophagosome, which fuses with lysosomes for digestion by lysosomal hydrolases. This process can promote cell survival by removing damaged organelles, but when damage is extensive, it can also be a mechanism of cell death. Similar to the Kessel and Agostinis laboratories, we have reported the vigorous induction of autophagy by PDT; this was found in human breast cancer MCF-7 cells whether or not they were able to efficiently induce apoptosis. One way to evaluate the role of autophagy in PDT-treated cells is to silence one of the essential genes in the pathway. Kessel and Reiners silenced the Atg7 gene of murine leukemia L1210 cells using inhibitory RNA and found sensitization to PDT-induced cell death at a low dose of PDT, implying that autophagy is protective when PDT damage is modest. We have examined the role of autophagy in an epithelium-derived cancer cell by comparing parental and Atg7-silenced MCF-7 cells to varying doses of PDT with the phthalocyanine photosensitizer Pc 4. In contrast to L1210 cells, autophagy-deficient MCF-7 cells were more resistant to the lethal effects of PDT, as judged by clonogenic assays. A possible explanation for the difference in outcome for L1210 vs. MCF-7 cells is the greatly reduced ability of the latter to undergo apoptosis, a deficiency that may convert autophagy into a cell-death process even at low PDT doses. Experiments to investigate the mechanism(s) responsible are in process.

  6. Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on survival rate and in vitro immune response.

    PubMed

    Fang, X; Jiang, C; Xia, Q

    2015-01-01

    The aim of this study was to investigate the effects of dendritic cell (DC) therapy in osteosarcoma. Bone marrow DCs from Wistar (allograft group) and Sprague Dawley (SD) (homograft group) rats were electrically fused with the SD-derived osteosarcoma cell line UMR106 to generate a DC-osteosarcoma fusion (DOF) tumor vaccine, which was co-incubated with SD T lymphocytes to stimulate T cell proliferation. CD8+ and CD4+ cell percentages were measured by flow cytometry; tumor-cytotoxic effects of cytotoxic T lymphocytes (CTLs) were measured by the MTT assay. Active immunotherapy was applied to SD osteosarcoma model rats via subcutaneous injection of the tumor vaccine. Significant potentiation of T lymphocyte proliferation was observed in both groups. In the homograft group, the CD8+/CD4+ ratio was elevated to 78.2 from 55.1% after stimulation (P < 0.05) whereas the CD4+ cell percentage was reduced from 61.3 to 21.2% (P < 0.05). Similarly, in the allograft group the CD8+ and CD4+ cell percentages significantly increased (33.8 to 69.6%) or decreased (61.3 to 28.1%) after stimulation, respectively (P < 0.05). The preferential homograft group response was not significant (P > 0.05). Induced UMR106- specific CTLs showed a significantly higher tumor-cytotoxic effect after stimulation (P < 0.05). After DOF active immunotherapy, tumor bodies displayed atrophy or disappearance, leading to higher survival times and rates (60 and 70% in the allograft and homograft groups) (P < 0.05). This study demonstrated that osteosarcoma immunotherapy using a DC-fused tumor vaccine can effectively stimulate T lymphocyte proliferation and induce the tumor-cytotoxic activity of CTLs. PMID:26436501

  7. Ebi, a Drosophila homologue of TBL1, regulates the balance between cellular defense responses and neuronal survival

    PubMed Central

    Lim, Young-Mi; Tsuda, Leo

    2016-01-01

    Transducin β-like 1 (TBL1), a transcriptional co-repressor complex, is a causative factor for late-onset hearing impairments. Transcriptional co-repressor complexes play pivotal roles in gene expression by making a complex with divergent transcription factors. However, it remained to be clarified how co-repressor complex regulates cellular survival. We herein demonstrated that ebi, a Drosophila homologue of TBL1, suppressed photoreceptor cell degeneration in the presence of excessive innate immune signaling. We also showed that the balance between NF-κB and AP-1 is a key component of cellular survival under stress conditions. Given that Ebi plays an important role in innate immune responses by regulating NF-κB activity and inhibition of apoptosis induced by associating with AP-1, it may be involved in the regulation of photoreceptor cell survival by modulating cross-talk between NF-κB and AP-1. PMID:27073743

  8. Preventing Ultraviolet Light-Induced Damage: The Benefits of Antioxidants

    ERIC Educational Resources Information Center

    Yip, Cheng-Wai

    2007-01-01

    Extracts of fruit peels contain antioxidants that protect the bacterium "Escherichia coli" against damage induced by ultraviolet light. Antioxidants neutralise free radicals, thus preventing oxidative damage to cells and deoxyribonucleic acid. A high survival rate of UV-exposed cells was observed when grapefruit or grape peel extract was added,…

  9. Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

    PubMed Central

    2011-01-01

    associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death. Conclusions Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme. PMID:21649900

  10. Exercise-related sudden cardiac arrest in London: incidence, survival and bystander response

    PubMed Central

    Edwards, Melanie J; Fothergill, Rachael T

    2015-01-01

    Objective The study aimed to (1) establish the incidence of exercise-related sudden cardiac arrest (SCA) in London, (2) investigate survival from exercise-related SCA and (3) examine factors related to survival. Method This retrospective observational study examined 2 years’ data from the London Ambulance Service (LAS) cardiac arrest registry for patients in whom resuscitation was attempted following an out-of-hospital cardiac arrest (OHCA), a cardiac cause was presumed and the arrest occurred during or within 1 h of exercise. Results The incidence of exercise-related SCA in London was estimated to be 0.6 per 100 000 person-years which equated to 0.5% of all OHCA, and 1.5% of all OHCA with presumed cardiac aetiology and resuscitation attempted. The majority of cases were male and the incidence increased from age 40 years. Just under one-third of patients survived to hospital discharge. Survival in the Utstein comparator group (cases with presumed cardiac aetiology, resuscitation attempted, bystander witnessed and a presenting cardiac rhythm of ventricular fibrillation or tachycardia) was higher at 42%. Survival was significantly associated with initial cardiac rhythm (χ2=17.5, df=2, p<0.001) and bystander defibrillation (Fisher's exact test, p<0.05). Conclusions Incidence of exercise-related SCA in the general population in London is rare. Survival following exercise-related SCA was considerably higher than survival for all OHCA with presumed cardiac aetiology and resuscitation attempted attended by the LAS during the same period. The major limitation of the study is the likely under identification of cases of exercise-related SCA. PMID:26468401

  11. Light-induced fading of the PSL signal from irradiated herbs and spices

    NASA Astrophysics Data System (ADS)

    Alberti, A.; Corda, U.; Fuochi, P.; Bortolin, E.; Calicchia, A.; Onori, S.

    2007-08-01

    Reliability of the photo-stimulated luminescence (PSL) technique, as screening method for irradiated food identification, has been tested with three kinds of herbs and spices (oregano, red pepper and fennel), prepared in two different ways (granular: i.e. seeds and flakes, or powdered), over a long period of storage with different light exposures. The irradiated samples kept in the dark gave always a positive response (the sample is correctly classified as "irradiated") for the overall examination period. The samples kept under ambient light conditions, in typical commercial glass containers, exhibited a reduction of the PSL signal, more or less pronounced depending on the type of food and packaging. The different PSL response of the irradiated samples is to be related to the quantity and quality of the mineral debris present in the individual food. It was also found that, for the same type of food, the light-induced fading was much stronger for the flaked and seed samples than for the corresponding powder samples, the penetrating capability of light being much more inhibited in powdered than in whole seeds or flaked form samples. The observed light bleaching of the PSL signal in irradiated herbs and spices is of practical relevance since it may lead to false negative classifications.

  12. Light Induced Processes for the Synthesis of Polymers With Complex Structures

    NASA Astrophysics Data System (ADS)

    Durmaz, Yasemin Y.; Tasdelen, M. Atilla; Aydogan, Binnur; Kahveci, Muhammet U.; Yagci, Yusuf

    Light induced reactions are based on the absorption of light that excites the electrons of a molecule and can, under favorable circumstances, lead to dissociation, isomerization, abstraction, electron or energy transfer, and bond formation. These reactions have been the subject of many studies in various fields including organic chemistry, molecular biology, electronics etc. Light induced reactions can advantageously be utilized in the field of polymer chemistry. Among them, light induced polymerization is of enormous commercial importance. Techniques such as curing of coatings on wood, metal and paper, adhesives, printing inks and photoresists are based on photopolymerization. There are some other interesting applications, including production of laser video discs and curing of acrylate dental fillings. In this chapter, general methods for the light induced polymerization processes involving radical and ionic reactions are described. Special emphasize is devoted to their application to more complex macromolecular structures such as block, graft and star copolymers, and polymer nanocomposites based on clay and metal.

  13. Analysis of different strategies adapted by two cassava cultivars in response to drought stress: ensuring survival or continuing growth.

    PubMed

    Zhao, Pingjuan; Liu, Pei; Shao, Jiaofang; Li, Chunqiang; Wang, Bin; Guo, Xin; Yan, Bin; Xia, Yiji; Peng, Ming

    2015-03-01

    Cassava is one of the most drought-tolerant crops, however, the underlying mechanism for its ability to survive and produce under drought remains obscure. In this study, two cassava cultivars, SC124 and Arg7, were treated by gradually reducing the soil water content. Their responses to the drought stress were examined through their morphological and physiological traits and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. SC124 plants adapted a 'survival' mode under mild drought stress as evidenced by early stomatal closure and a reduction in the levels of various photosynthetic proteins and photosynthetic capacity, resulting in early growth quiescence. In contrast, Arg7 plants underwent senescence of older leaves but continued to grow, although at a reduced rate, under mild drought. SC124 plants were more capable of surviving prolonged severe drought than Arg7. The iTRAQ analysis identified over 5000 cassava proteins. Among the drought-responsive proteins identified in the study were an aquaporin, myo-inositol 1-phosphate synthases, and a number of proteins involved in the antioxidant systems and secondary metabolism. Many proteins that might play a role in signalling or gene regulation were also identified as drought-responsive proteins, which included several protein kinases, two 14-3-3 proteins, several RNA-binding proteins and transcription factors, and two histone deacetylases. Our study also supports the notion that linamarin might play a role in nitrogen reallocation in cassava under drought. PMID:25547914

  14. Dihydroxyselenolane (DHS) supplementation improves survival following whole-body irradiation (WBI) by suppressing tissue-specific inflammatory responses.

    PubMed

    Kunwar, Amit; Verma, Prachi; Bhilwade, H N; Iwaoka, Michio; Priyadarsini, K Indira

    2016-09-01

    Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival). DHS treatment, despite inducing expression of glutathione peroxidases (GPx1, GPx2, and GPx4) in spleen and intestine, did not protect against radiation-induced acute (10-day) haematopoietic and gastrointestinal toxicities. DHS treatment significantly reduced radiation-induced DNA damage in peripheral leukocytes and inflammatory responses in intestine, lung, and circulation. The anti-inflammatory effect of DHS was associated with reductions in lipid peroxidation, expression of pro-inflammatory genes such as Icam-1, Ccl-2, and iNos-2, and subsequent infiltration of inflammatory cells. Irradiated mice treated with DHS survived until day 30 post-irradiation and showed restoration of spleen cellularity and intestinal villi, but had moderately increased systemic and tissue-specific inflammatory responses. Another organoselenium compound, selenomethionine, evaluated in parallel with DHS at the same dose and treatment schedule, showed comparable radioprotective effects. The mechanism of radioprotection by DHS is mainly via suppression of inflammatory responses. PMID:27542713

  15. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Jabbour, Elias; Sasaki, Koji; Patel, Keyur; O'Brien, Susan M; Cortes, Jorge E; Garris, Rebecca; Issa, Ghayas C; Garcia-Manero, Guillermo; Luthra, Rajyalakshmi; Thomas, Deborah; Kantarjian, Hagop; Ravandi, Farhad

    2016-07-28

    The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph(+) ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph(+) ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT. PMID:27235138

  16. Red-light-induced positive phototropism in Arabidopsis roots

    NASA Technical Reports Server (NTRS)

    Ruppel, N. J.; Hangarter, R. P.; Kiss, J. Z.

    2001-01-01

    The interaction between light and gravity is critical in determining the final form of a plant. For example, the competing activities of gravitropism and phototropism can determine the final orientation of a stem or root. The results reported here indicate that, in addition to the previously described blue-light-dependent negative phototropic response in roots, roots of Arahidopsis thaliana (L.) Heynh. display a previously unknown red-light-dependent positive phototropic response. Both phototropic responses in roots are considerably weaker than the graviresponse, which often masks phototropic curvature. However, through the use of mutant strains with impaired gravitropism, we were able to identify a red-light-dependent positive phototropic response in Arabidopsis roots. The red-induced positive phototropic response is considerably weaker than the blue-light response and is barely detectable in plants with a normal gravitropic response.

  17. Emerging role of angiogenin in stress response and cell survival under adverse conditions

    PubMed Central

    Li, Shuping; Hu, Guo-Fu

    2011-01-01

    Angiogenin (ANG), also known as ribonuclease (RNASE) 5, is a member of the vertebrate-specific, secreted RNASE superfamily. ANG was originally identified as a tumor angiogenic factor, but its biological activity has been extended from inducing angiogenesis to stimulating cell proliferation and more recently, to promoting cell survival. Under growth conditions, ANG is translocated to nucleus where it accumulates in nucleolus and stimulates ribosomal RNA (rRNA) transcription, thus facilitating cell growth and proliferation. Under stress conditions, ANG is accumulated in cytoplasmic compartments and modulates the production of tiRNA, a novel class of small RNA that is derived from tRNA and is induced by stress. tiRNA suppress global protein translation by inhibiting both cap-dependent and -independent translation including that mediated by weak IRESes. However, strong IRES-mediated translation, a mechanism often used by genes involved in pro-survival and anti-apoptosis, is not affected. Thus, ANG-mediated tiRNA reprogram protein translation, save anabolic energy, and promote cell survival. This recently uncovered function of ANG presents a novel mechanism of action in regulating cell growth and survival. PMID:22021078

  18. Adaptive Memory: Determining the Proximate Mechanisms Responsible for the Memorial Advantages of Survival Processing

    ERIC Educational Resources Information Center

    Burns, Daniel J.; Burns, Sarah A.; Hwang, Ana J.

    2011-01-01

    J. S. Nairne, S. R. Thompson, and J. N. S. Pandeirada (2007) suggested that our memory systems may have evolved to help us remember fitness-relevant information and showed that retention of words rated for their relevance to survival is superior to that of words encoded under other deep processing conditions. The authors present 4 experiments that…

  19. Dissecting the proteome dynamics of the early heat stress response leading to plant survival or death in Arabidopsis.

    PubMed

    Echevarría-Zomeño, Sira; Fernández-Calvino, Lourdes; Castro-Sanz, Ana B; López, Juan Antonio; Vázquez, Jesús; Castellano, M Mar

    2016-06-01

    In many plant species, an exposure to a sublethal temperature triggers an adaptative response called acclimation. This response involves an extensive molecular reprogramming that allows the plant to further survive to an otherwise lethal increase of temperature. A related response is also launched under an abrupt and lethal heat stress that, in this case, is unable to successfully promote thermotolerance and therefore ends up in plant death. Although these molecular programmes are expected to have common players, the overlapping degree and the specific regulators of each process are currently unknown. We have carried out a high-throughput comparative proteomics analysis during acclimation and during the early stages of the plant response to a severe heat stress that lead Arabidopsis seedlings either to survival or death. This analysis dissects these responses, unravels the common players and identifies the specific proteins associated with these different fates. Thermotolerance assays of mutants in genes with an uncharacterized role in heat stress demonstrate the relevance of this study to uncover both positive and negative heat regulators and pinpoint a pivotal role of JR1 and BAG6 in heat tolerance. PMID:26580143

  20. Genetic polymorphisms in circadian negative feedback regulation genes predict overall survival and response to chemotherapy in gastric cancer patients

    PubMed Central

    Qu, Falin; Qiao, Qing; Wang, Nan; Ji, Gang; Zhao, Huadong; He, Li; Wang, Haichao; Bao, Guoqiang

    2016-01-01

    Circadian negative feedback loop (CNFL) genes play important roles in cancer development and progression. To evaluate the effects of single nucleotide polymorphisms (SNPs) in CNFL genes on the survival of GC patients, 13 functional SNPs from 5 CNFL genes were genotyped in a cohort of 1030 resected GC patients (704 in the training set, 326 in the validation set) to explore the association of SNPs with overall survival (OS). Among the 13 SNPs, three SNPs (rs1056560 in CRY1, rs3027178 in PER1 and rs228729 in PER3) were significantly associated with OS of GC in the training set, and verified in the validation set and pooled analysis. Furthermore, a dose-dependent cumulative effect of these SNPs on GC survival was observed, and survival tree analysis showed higher order interactions between these SNPs. In addition, protective effect conferred by adjuvant chemotherapy (ACT) on GC was observed in patients with variant alleles (TG/GG) of rs1056560, but not in those with homozygous wild (TT) genotype. Functional assay suggested rs1056560 genotypes significantly affect CRY1 expression in cancer cells. Our study presents that SNPs in the CNFL genes may be associated with GC prognosis, and provides the guidance in selecting potential GC patients most likely responsive to ACT. PMID:26927666

  1. Multi-level Modeling of Light-Induced Stomatal Opening Offers New Insights into Its Regulation by Drought

    PubMed Central

    Sun, Zhongyao; Jin, Xiaofen; Albert, Réka; Assmann, Sarah M.

    2014-01-01

    Plant guard cells gate CO2 uptake and transpirational water loss through stomatal pores. As a result of decades of experimental investigation, there is an abundance of information on the involvement of specific proteins and secondary messengers in the regulation of stomatal movements and on the pairwise relationships between guard cell components. We constructed a multi-level dynamic model of guard cell signal transduction during light-induced stomatal opening and of the effect of the plant hormone abscisic acid (ABA) on this process. The model integrates into a coherent network the direct and indirect biological evidence regarding the regulation of seventy components implicated in stomatal opening. Analysis of this signal transduction network identified robust cross-talk between blue light and ABA, in which [Ca2+]c plays a key role, and indicated an absence of cross-talk between red light and ABA. The dynamic model captured more than 1031 distinct states for the system and yielded outcomes that were in qualitative agreement with a wide variety of previous experimental results. We obtained novel model predictions by simulating single component knockout phenotypes. We found that under white light or blue light, over 60%, and under red light, over 90% of all simulated knockouts had similar opening responses as wild type, showing that the system is robust against single node loss. The model revealed an open question concerning the effect of ABA on red light-induced stomatal opening. We experimentally showed that ABA is able to inhibit red light-induced stomatal opening, and our model offers possible hypotheses for the underlying mechanism, which point to potential future experiments. Our modelling methodology combines simplicity and flexibility with dynamic richness, making it well suited for a wide class of biological regulatory systems. PMID:25393147

  2. Multi-level modeling of light-induced stomatal opening offers new insights into its regulation by drought.

    PubMed

    Sun, Zhongyao; Jin, Xiaofen; Albert, Réka; Assmann, Sarah M

    2014-11-01

    Plant guard cells gate CO2 uptake and transpirational water loss through stomatal pores. As a result of decades of experimental investigation, there is an abundance of information on the involvement of specific proteins and secondary messengers in the regulation of stomatal movements and on the pairwise relationships between guard cell components. We constructed a multi-level dynamic model of guard cell signal transduction during light-induced stomatal opening and of the effect of the plant hormone abscisic acid (ABA) on this process. The model integrates into a coherent network the direct and indirect biological evidence regarding the regulation of seventy components implicated in stomatal opening. Analysis of this signal transduction network identified robust cross-talk between blue light and ABA, in which [Ca2+]c plays a key role, and indicated an absence of cross-talk between red light and ABA. The dynamic model captured more than 10(31) distinct states for the system and yielded outcomes that were in qualitative agreement with a wide variety of previous experimental results. We obtained novel model predictions by simulating single component knockout phenotypes. We found that under white light or blue light, over 60%, and under red light, over 90% of all simulated knockouts had similar opening responses as wild type, showing that the system is robust against single node loss. The model revealed an open question concerning the effect of ABA on red light-induced stomatal opening. We experimentally showed that ABA is able to inhibit red light-induced stomatal opening, and our model offers possible hypotheses for the underlying mechanism, which point to potential future experiments. Our modelling methodology combines simplicity and flexibility with dynamic richness, making it well suited for a wide class of biological regulatory systems. PMID:25393147

  3. Cell therapy for Parkinson's disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts.

    PubMed

    Wenker, Shirley D; Leal, María Celeste; Farías, María Isabel; Zeng, Xianmin; Pitossi, Fernando J

    2016-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder, whose cardinal pathology is the loss of dopaminergic neurons in the substantia nigra. Current treatments for PD have side effects in the long term and do not halt disease progression or regenerate dopaminergic cell loss. Attempts to compensate neuronal cell loss by transplantation of dopamine-producing cells started more than 30 years ago, leading to several clinical trials. These trials showed safety and variable efficacy among patients. In addition to variability in efficacy, several patients developed graft-induced dyskinesia. Nevertheless, they have provided a proof of concept that motor symptoms could be improved by cell transplantation. Cell transplantation in the brain presents several immunological challenges. The adaptive immune response should be abolished to avoid graft rejection by the host. In addition, the innate immune response will always be present after transplanting cells into the brain. Remarkably, the innate immune response can have dramatic effects on the survival, differentiation and proliferation of the transplanted cells, but has been hardly investigated. In this review, we analyze data on the functional effects of signals from the innate immune system on dopaminergic differentiation, survival and proliferation. Then, we discussed efforts on cell transplantation in animal models and PD patients, highlighting the immune response and the immunomodulatory treatment strategies performed. The analysis of the available data lead us to conclude that the modulation of the innate immune response after transplantation can increase the success of future clinical trials in PD by enhancing cell differentiation and survival. This article is part of a Special Issue entitled SI: PSC and the brain. PMID:26239914

  4. Molecular models predict light-induced glutamine tautomerization in BLUF photoreceptors.

    PubMed

    Domratcheva, Tatiana; Grigorenko, Bella L; Schlichting, Ilme; Nemukhin, Alexander V

    2008-05-15

    The recently discovered photoreceptor proteins containing BLUF (sensor of blue light using FAD) domains mediate physiological responses to blue light in bacteria and euglena. In BLUF domains, blue light activates the flavin chromophore yielding a signaling state characterized by a approximately 10 nm red-shifted absorption. We developed molecular models for the dark and light states of the BLUF domain of the Rhodobacter sphaeroides AppA protein, which are based on the crystal structures and quantum-mechanical simulations. According to these models, photon absorption by the flavin results in a tautomerization and 180 degree rotation of the Gln side chain that interacts with the flavin cofactor. This chemical modification of the Gln residue induces alterations in the hydrogen bond network in the core of the photoreceptor domain, which were observed in numerous spectroscopic experiments. The calculated electronic transition energies and vibrational frequencies of the proposed dark and light states are consistent with the optical and IR spectral changes observed during the photocycle. Light-induced isomerization of an amino acid residue instead of a chromophore represents a feature that has not been described previously in photoreceptors. PMID:18263659

  5. Visible-light-induced instability in amorphous metal-oxide based TFTs for transparent electronics

    SciTech Connect

    Ha, Tae-Jun

    2014-10-15

    We investigate the origin of visible-light-induced instability in amorphous metal-oxide based thin film transistors (oxide-TFTs) for transparent electronics by exploring the shift in threshold voltage (V{sub th}). A large hysteresis window in amorphous indium-gallium-zinc-oxide (a-IGZO) TFTs possessing large optical band-gap (≈3 eV) was observed in a visible-light illuminated condition whereas no hysteresis window was shown in a dark measuring condition. We also report the instability caused by photo irradiation and prolonged gate bias stress in oxide-TFTs. Larger V{sub th} shift was observed after photo-induced stress combined with a negative gate bias than the sum of that after only illumination stress and only negative gate bias stress. Such results can be explained by trapped charges at the interface of semiconductor/dielectric and/or in the gate dielectric which play a role in a screen effect on the electric field applied by gate voltage, for which we propose that the localized-states-assisted transitions by visible-light absorption can be responsible.

  6. Visible light induced photoelectrochemical biosensing based on oxygen-sensitive quantum dots.

    PubMed

    Wang, Wenjing; Bao, Lei; Lei, Jianping; Tu, Wenwen; Ju, Huangxian

    2012-09-26

    A visible light induced photoelectrochemical biosensing platform based on oxygen-sensitive near-infrared quantum dots (NIR QDs) was developed for detection of glucose. The NIR QDs were synthesized in an aqueous solution, and characterized with scanning electron microscopy and X-ray photoelectron spectroscopy. The as-prepared NIR QDs were employed to construct oxygen-sensitive photoelectrochemical biosensor on a fluorine-doped tin oxide (FTO) electrode. The oxygen dependency of the photocurrent was investigated at as-prepared electrode, which demonstrated the signal of photocurrent is suppressed with the decreasing of oxygen. Coupling with the consumption of oxygen during enzymatic reaction, a photoelectrochemical strategy was proposed for the detection of substrate. Using glucose oxidase (GOx) as a model enzyme, that is, GOx was covalently attached to the surface of CdTe QDs, the resulting biosensor showed the sensitive response to glucose. Under the irradiation of visible light of a wavelength at 505 nm, the proposed photoelectrochemical method could detect glucose ranging from 0.1 mM to 11 mM with a detection limit of 0.04 mM. The photoelectrochemical biosensor showed a good performance with high upper detection limit, acceptable stability and accuracy, providing an alternative method for monitoring biomolecules and extending the application of near-infrared QDs. PMID:22935371

  7. Evolution of light-induced vapor generation at a liquid-immersed metallic nanoparticle

    PubMed Central

    Zhen, Yu-Rong; Neumann, Oara; Polman, Albert; García de Abajo, F. Javier

    2013-01-01

    When an Au nanoparticle in a liquid medium is illuminated with resonant light of sufficient intensity, a nanometer scale envelope of vapor -a “nanobubble”- surrounding the particle, is formed. This is the nanoscale onset of the well-known process of liquid boiling, occurring at a single nanoparticle nucleation site, resulting from the photothermal response of the nanoparticle. Here we examine bubble formation at an individual metallic nanoparticle in detail. Incipient nanobubble formation is observed by monitoring the plasmon resonance shift of an individual, illuminated Au nanoparticle, when its local environment changes from liquid to vapor. The temperature on the nanoparticle surface is monitored during this process, where a dramatic temperature jump is observed as the nanoscale vapor layer thermally decouples the nanoparticle from the surrounding liquid. By increasing the intensity of the incident light or decreasing the interparticle separation, we observe the formation of micron sized bubbles resulting from the coalescence of nanoparticle-“bound” vapor envelopes. These studies provide the first direct and quantitative analysis of the evolution of light-induced steam generation by nanoparticles from the nanoscale to the macroscale, a process that is of fundamental interest for a growing number of applications. PMID:23517407

  8. Evolution of light-induced vapor generation at a liquid-immersed metallic nanoparticle.

    PubMed

    Fang, Zheyu; Zhen, Yu-Rong; Neumann, Oara; Polman, Albert; García de Abajo, F Javier; Nordlander, Peter; Halas, Naomi J

    2013-04-10

    When an Au nanoparticle in a liquid medium is illuminated with resonant light of sufficient intensity, a nanometer scale envelope of vapor-a "nanobubble"-surrounding the particle, is formed. This is the nanoscale onset of the well-known process of liquid boiling, occurring at a single nanoparticle nucleation site, resulting from the photothermal response of the nanoparticle. Here we examine bubble formation at an individual metallic nanoparticle in detail. Incipient nanobubble formation is observed by monitoring the plasmon resonance shift of an individual, illuminated Au nanoparticle, when its local environment changes from liquid to vapor. The temperature on the nanoparticle surface is monitored during this process, where a dramatic temperature jump is observed as the nanoscale vapor layer thermally decouples the nanoparticle from the surrounding liquid. By increasing the intensity of the incident light or decreasing the interparticle separation, we observe the formation of micrometer-sized bubbles resulting from the coalescence of nanoparticle-"bound" vapor envelopes. These studies provide the first direct and quantitative analysis of the evolution of light-induced steam generation by nanoparticles from the nanoscale to the macroscale, a process that is of fundamental interest for a growing number of applications. PMID:23517407

  9. Differential response in chick survival to diet in least and crested auklets

    USGS Publications Warehouse

    Gall, A.E.; Roby, D.D.; Irons, D.B.; Rose, I.C.

    2006-01-01

    Least auklets Aethia pusilla and crested auklets A. cristatella are abundant planktivorous seabirds found throughout the Bering Sea and are inextricably linked to the secondary productivity of this northern marine ecosystem. We assessed the relationship between productivity and diet in least and crested auklets by examining breeding chronology, daily survival rates (DSR) of chicks, and nestling diet composition at 2 mixed colonies on St. Lawrence Island in the northern Bering Sea during the 2000 to 2002 breeding seasons. Nestlings of both least and crested auklets hatched earlier, had higher survival rates, and were fed more of the large, oceanic copepod Neocalanus cristatus in 2002 compared to the 2 yr of lower chick survival. In contrast, during the year of lowest DSR for both auklet species (2001), the small copepod Calanus marshallae was more prevalent in the diet of least auklets and the mid-sized copepod N. flemingeri was more prevalent in the diet of crested auklets compared to the other 2 yr. The prevalence of oceanic copepods in meals fed to chicks explained much of the annual variation in DSR in least auklets. Interannual differences in timing of nest initiation, nest survival, and diet of least and crested auklets may be associated with the strength of the cold, nutrient-rich Anadyr Current, which passes in close proximity to St. Lawrence Island and has important influences on zooplankton productivity and distribution. Auklet productivity and diet composition may serve as key indicators in the overall effort to monitor the impact of climate change on the productivity of the Bering Sea. ?? Inter-Research 2006.

  10. Forster's tern chick survival in response to a managed relocation of predatory California gulls

    USGS Publications Warehouse

    Ackerman, Joshua T.; Herzog, Mark P.; Hartman, C. Alex; Herring, Garth

    2014-01-01

    Gull populations can severely limit the productivity of waterbirds. Relocating gull colonies may reduce their effects on nearby breeding waterbirds, but there are few examples of this management strategy. We examined gull predation and survival of Forster's tern (Sterna forsteri) chicks before (2010) and after (2011) the managed relocation of the largest California gull (Larus californicus) colony (24,000 adults) in San Francisco Bay, California. Overall, survival of radio-marked Forster's tern chicks from hatching to fledging was 0.22 ± 0.03 (mean ± SE), and daily survival rates increased with age. Gulls were the predominant predator of tern chicks, potentially causing 54% of chick deaths. Prior to the gull colony relocation, 56% of radio-marked and 20% of banded tern chicks from the nearest tern colony were recovered dead in the gull colony, compared to only 15% of radio-marked and 4% of banded chicks recovered dead from all other tern colonies. The managed relocation of the gull colony substantially increased tern chick survival (by 900%) in the nearby (3.8 km) reference tern colony (0.29 ± 0.10 in 2010 and 0.25 ± 0.09 in 2011). Among 19 tern nesting islands, fledging success was higher when gull abundance was lower at nearby colonies and when gull colonies were farther from the tern colony. Our results indicate that the managed relocation of gull colonies away from preferred nesting areas of sensitive waterbirds can improve local reproductive success, but this conservation strategy may shift gull predation pressure to other areas or species.

  11. The ROP2-RIC7 pathway negatively regulates light-induced stomatal opening by inhibiting exocyst subunit Exo70B1 in Arabidopsis.

    PubMed

    Hong, Daewoong; Jeon, Byeong Wook; Kim, Soo Young; Hwang, Jae-Ung; Lee, Youngsook

    2016-01-01

    Stomata are the tiny valves on the plant surface that mediate gas exchange between the plant and its environment. Stomatal opening needs to be tightly regulated to facilitate CO2 uptake and prevent excess water loss. Plant Rho-type (ROP) GTPase 2 (ROP2) is a molecular component of the system that negatively regulates light-induced stomatal opening. Previously, ROP-interactive Cdc42- and Rac-interactive binding motif-containing protein 7 (RIC7) was suggested to function downstream of ROP2. However, the underlying molecular mechanism remains unknown. To understand the mechanism by which RIC7 regulates light-induced stomatal opening, we analyzed the stomatal responses of ric7 mutant Arabidopsis plants and identified the target protein of RIC7 using a yeast two-hybrid screen. Light-induced stomatal opening was promoted by ric7 knockout, whereas it was inhibited by RIC7 overexpression, indicating that RIC7 negatively regulates stomatal opening in Arabidopsis. RIC7 interacted with exocyst subunit Exo70 family protein B1 (Exo70B1), a component of the vesicle trafficking machinery. RIC7 and Exo70B1 localized to the plasma membrane region under light or constitutively active ROP2 conditions. The knockout mutant of Exo70B1 and ric7/exo70b1 exhibited retarded light-induced stomatal opening. Our results suggest that ROP2 and RIC7 suppress excess stomatal opening by inhibiting Exo70B1, which most likely participates in the vesicle trafficking required for light-induced stomatal opening. PMID:26451971

  12. Survival and physiologic response of Common Amakihi and Japanese White-eyes during simulated translocation

    USGS Publications Warehouse

    Work, T.M.; Massey, J.G.; Johnson, L.; Dougill, S.; Banko, P.C.

    1999-01-01

    We evaluated the effects of three translocation trials on Common Amakihi (Hemignathus virens) and Japanese White-eyes (Zosterops japonicus). Trial 1 involved capturing birds, transporting them on rough roads for 4 hr followed by holding in an aviary for 48 hr without overnight thermal support prior to release. Trial 2 involved capture, then holding in an aviary for 48 hr with overnight thermal support followed by transport for 4 hr prior to release. Trial 3 and 1 were identical except that overnight thermal support was provided during trial 3. We monitored survival, food consumption, weight change, and fecal production during captivity as well as changes in hematocrit, estimated total solids, heterophil to lymphocyte ratios, plasma uric acid, and creatinine phosphokinase (CPK) at capture and release. Survival was significantly lower for Amakihi during trial I (no thermal support). Birds that died lost significantly more weight than those that survived. Regardless of trial, birds responded to translocation by a combination of weight loss, anemia, hypoproteinemia, and elevated heterophil to lymphocyte ratio, uric acid, and CPK levels. The first 24 hr of captivity posed the greatest risk to birds regardless of whether transport or holding occurred first. Food consumption, fecal production, and weight all decreased at night, and overnight thermal support during holding was critical if ambient temperatures dipped to freezing. We recommend that if small passerines are to be held for > 12 hr, they be monitored individually for weight loss, food consumption, and fecal production.

  13. Survival and physiologic response of common Amakihi and Japanese white-eyes during simulated translocation

    USGS Publications Warehouse

    Work, T.M.; Massey, J.G.; Johnson, L.; Dougill, S.; Banko, P.C.

    1999-01-01

    We evaluated the effects of three translocation trials on Common Amakihi (Hemignathus virens) and Japanese White-eyes (Zosterops japonicus). Trial 1 involved capturing birds, transporting them on rough roads for 4 hr followed by holding in an aviary for 48 hr without overnight thermal support prior to release. Trial 2 involved capture, then holding in an aviary for 48 hr with overnight thermal support followed by transport for 4 hr prior to release. Trial 3 and 1 were identical except that overnight thermal support was provided during trial 3. We monitored survival, food consumption, weight change, and fecal production during captivity as well as changes in hematocrit, estimated total solids, heterophil to lymphocyte ratios, plasma uric acid, and creatinine phosphokinase (CPK) at capture and release. Survival was significantly lower for Amakihi during trial 1 (no thermal support). Birds that died lost significantly more weight than those that survived. Regardless of trial, birds responded to translocation by a combination of weight loss, anemia, hypoproteinemia, and elevated heterophil to lymphocyte ratio, uric acid, and CPK levels. The first 24 hr of captivity posed the greatest risk to birds regardless of whether transport or holding occurred first. Food consumption, fecal production, and weight all decreased at night, and overnight thermal support during holding was critical if ambient temperatures dipped to freezing. We recommend that if small passerines are to be held for > 12 hr, they be monitored individually for weight loss, food consumption, and fecal production.

  14. Mechanisms of survival, responses and sources of Salmonella in low-moisture environments

    PubMed Central

    Finn, Sarah; Condell, Orla; McClure, Peter; Amézquita, Alejandro; Fanning, Séamus

    2013-01-01

    Some Enterobacteriaceae possess the ability to survive in low-moisture environments for extended periods of time. Many of the reported food-borne outbreaks associated with low-moisture foods involve Salmonella contamination. The control of Salmonella in low-moisture foods and their production environments represents a significant challenge for all food manufacturers. This review summarizes the current state of knowledge with respect to Salmonella survival in intermediate- and low-moisture food matrices and their production environments. The mechanisms utilized by this bacterium to ensure their survival in these dry conditions remain to be fully elucidated, however, in depth transcriptomic data is now beginning to emerge regarding this observation. Earlier research work described the effect(s) that low-moisture can exert on the long-term persistence and heat tolerance of Salmonella, however, data are also now available highlighting the potential cross-tolerance to other stressors including commonly used microbicidal agents. Sources and potential control measures to reduce the risk of contamination will be explored. By extending our understanding of these geno- and phenotypes, we may be able to exploit them to improve food safety and protect public health. PMID:24294212

  15. Mechanisms of survival, responses and sources of Salmonella in low-moisture environments.

    PubMed

    Finn, Sarah; Condell, Orla; McClure, Peter; Amézquita, Alejandro; Fanning, Séamus

    2013-01-01

    Some Enterobacteriaceae possess the ability to survive in low-moisture environments for extended periods of time. Many of the reported food-borne outbreaks associated with low-moisture foods involve Salmonella contamination. The control of Salmonella in low-moisture foods and their production environments represents a significant challenge for all food manufacturers. This review summarizes the current state of knowledge with respect to Salmonella survival in intermediate- and low-moisture food matrices and their production environments. The mechanisms utilized by this bacterium to ensure their survival in these dry conditions remain to be fully elucidated, however, in depth transcriptomic data is now beginning to emerge regarding this observation. Earlier research work described the effect(s) that low-moisture can exert on the long-term persistence and heat tolerance of Salmonella, however, data are also now available highlighting the potential cross-tolerance to other stressors including commonly used microbicidal agents. Sources and potential control measures to reduce the risk of contamination will be explored. By extending our understanding of these geno- and phenotypes, we may be able to exploit them to improve food safety and protect public health. PMID:24294212

  16. Survival and behavioural response to acaricides of the coconut mite predator Neoseiulus baraki.

    PubMed

    Lima, Debora B; Melo, José W S; Guedes, Raul N C; Siqueira, Herbert A A; Pallini, Angelo; Gondim, Manoel G C

    2013-07-01

    The coconut mite, Aceria guerreronis Keifer, is a major pest of coconut palm in the world. The control of this pest species is done through acaricide applications at short time intervals. However, the predators of this pest may also be affected by acaricides. Among the predators of A. guerreronis, Neoseiulus baraki (Athias-Henriot) has potential for biological control. The objective of this study was to assess the effect of acaricides on the survival and behavior of N. baraki. The survivorship of N. baraki was recorded in surface-impregnated arenas. Choice and no-choice behavioral bioassays were carried out using a video tracking system to assess the walking behavior of the predator under acaricide exposure. Although all acaricides negatively affected the survival of N. baraki, chlorfenapyr and azadirachtin caused lower effect than the other acaricides. No significant differences in walking behavior were observed under exposure to fenpyroximate, chlorfenapyr and chlorpyrifos on fully-contaminated arenas. Azadirachtin and chlorpyrifos caused repellence. Irritability was observed for all acaricides, except for abamectin. Chlorfenapyr was the most suitable product for managing the coconut mite because of its low effect on survival and behavior of N. baraki. PMID:23224672

  17. Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

    NASA Astrophysics Data System (ADS)

    Ghita, Mihaela; Coffey, Caroline B.; Butterworth, Karl T.; McMahon, Stephen J.; Schettino, Giuseppe; Prise, Kevin M.

    2016-01-01

    To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

  18. Survival and behavior of Chinese mystery snails (Bellamya chinensis) in response to simulated water body drawdowns and extended air exposure

    USGS Publications Warehouse

    Unstad, Kody M.; Uden, Daniel R.; Allen, Craig R.; Chaine, Noelle M.; Haak, Danielle M.; Kill, Robert A.; Pope, Kevin L.; Stephen, Bruce J.; Wong, Alec

    2013-01-01

    Nonnative invasive mollusks degrade aquatic ecosystems and induce economic losses worldwide. Extended air exposure through water body drawdown is one management action used for control. In North America, the Chinese mystery snail (Bellamya chinensis) is an invasive aquatic snail with an expanding range, but eradication methods for this species are not well documented. We assessed the ability of B. chinensis to survive different durations of air exposure, and observed behavioral responses prior to, during, and following desiccation events. Individual B. chinensis specimens survived air exposure in a laboratory setting for > 9 weeks, and survivorship was greater among adults than juveniles. Several B. chinensis specimens responded to desiccation by sealing their opercula and/or burrowing in mud substrate. Our results indicate that drawdowns alone may not be an effective means of eliminating B. chinensis. This study lays the groundwork for future management research that may determine the effectiveness of drawdowns when combined with factors such as extreme temperatures, predation, or molluscicides.

  19. Trichinella spiralis infection changes immune response in mice performed abdominal heterotopic cardiac transplantation and prolongs cardiac allograft survival time.

    PubMed

    Deng, Gengguo; Deng, Ronghai; Yao, Jianping; Liao, Bing; Chen, Yinghua; Wu, Zhongdao; Hu, Hongxing; Zhou, Xingwang; Ma, Yi

    2016-01-01

    Allograft rejection has been an obstacle for long-term survival of patients for many years. Current strategies for transplant rejection are not as optimal as we expected, especially for long-term treatments. Trichinella spiralis, a nematode parasitized in mammalian muscle and as an invader, maintains harmonious with host in the long term by evading host immune attack. To determine whether T. spiralis infection impacts on allograft rejection, we performed mice cardiac allograft transplantation model by using BALB/c (H-2(b)) mice as donors and C57BL/6 (H-2(b)) mice orally infected with 300 muscle larvae for 28 days as recipients. Graft survival was monitored by daily palpation of the abdomen; histologic change was observed by H&E stain; and CD4(+), CD8(+), CD4(+)IFN-γ(+), and CD4(+)IL-17(+) T cells and regulatory T cells were examined with the use of flow cytometry. Serum cytokine levels were measured by Luminex. Finally, we found that mean survival time of cardiac allografts in T. spiralis group was 23.40 ± 1.99 days, while the vehicle control group was 10.60 ± 0.75 days. Furthermore, we observed alleviated histological changes in the heart allograft, decreased corresponding CD8(+) T cells, suppressed Th1 and Th17 responses, and increased regulatory T cell frequency in a murine cardiac transplantation model at day 7 post-transplantation in experimental group. These data suggest that T. spiralis infection resulted in prolonged allograft survival following murine cardiac transplantation, with suppressed Th1/Th17 responses and augmented regulatory T cells. PMID:26481486

  20. Family Growth and Survival Response to Two Simulated Water Temperature Environments in the Sea Urchin Strongylocentrotus intermedius.

    PubMed

    Chang, Yaqing; Tian, Xiaofei; Zhang, Weijie; Han, Fenjie; Chen, Shun; Zhou, Mi; Pang, Zhenguo; Qi, Shoubing; Feng, Wenping

    2016-01-01

    Heat tolerance is a target trait in the selective breeding of the sea urchin Strongylocentrotus intermedius, as it plays an important role in the survival and growth of cultured S. intermedius during summer. We investigated family growth and survival response to two temperature treatments to evaluate the genotype by temperature interaction (GEI) in the family selection of S. intermedius. Sea urchins from 11 families were exposed to two simulated water temperature environments-high temperature (HE) and control temperature (CE)-for 12 months, with each experiment divided into four periods (P1, stress-free period I; P2, stress-full high period; P3, stress-response period; and P4, stress-free period II) based on the temperature changes and the survival. Test diameter (TD), body weight (BW), and survival rate (SR) in HE and CE were measured monthly. Effects of family, temperature, and family-temperature interaction on TD, BW, SR, and specific growth rate (SGR) for BW were examined. In CE, BW differed significantly between families in P2, P3, and P4, while TD differed significantly between families in P3 and P4 (p < 0.05). In HE, family had significant effects on BW in P4, and on TD in P3 and P4, while temperature had significant effects on SR, TD, and BW in P3 and P4 (p < 0.05). GEI effects were not significant for TD or BW; however, family ranking changes revealed the existence of GEI in SR. The GEI results indicate the necessity of applying family selection in CE and HE for SR, but not for TD or BW. These results may provide a guide for aquaculture and selective breeding of S. intermedius under temperature pressure. PMID:27589722

  1. Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

    PubMed

    Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

    2016-06-01

    Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed. PMID:26967458

  2. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

    USGS Publications Warehouse

    Busch, Joseph D.; Van Andel, Roger; Stone, Nathan E.; Cobble, Kacy R.; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William E.; Shuey, Megan M.; Foster, Jeffrey T.; Schupp, James M.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L.; Rocke, Tonie E.; Wagner, David M.

    2013-01-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  3. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs.

    PubMed

    Busch, Joseph D; Van Andel, Roger; Stone, Nathan E; Cobble, Kacy R; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William; Shuey, Megan M; Foster, Jeffrey T; Schupp, James M; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L; Rocke, Tonie E; Wagner, David M

    2013-10-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies. PMID:24502719

  4. Superwetting of TiO2 by light-induced water-layer growth via delocalized surface electrons

    PubMed Central

    Lee, Kunyoung; Kim, QHwan; An, Sangmin; An, JeongHoon; Kim, Jongwoo; Kim, Bongsu; Jhe, Wonho

    2014-01-01

    Titania, which exhibits superwetting under light illumination, has been widely used as an ideal material for environmental solution such as self-cleaning, water–air purification, and antifogging. There have been various studies to understand such superhydrophilic conversion. The origin of superwetting has not been clarified in a unified mechanism yet, which requires direct experimental investigation of the dynamic processes of water-layer growth. We report in situ measurements of the growth rate and height of the photo-adsorbed water layers by tip-based dynamic force microscopy. For nanocrystalline anatase and rutile TiO2 we observe light-induced enhancement of the rate and height, which decrease after O2 annealing. The results lead us to confirm that the long-range attraction between water molecules and TiO2, which is mediated by delocalized electrons in the shallow traps associated with O2 vacancies, produces photo-adsorption of water on the surface. In addition, molecular dynamics simulations clearly show that such photo-adsorbed water is critical to the zero contact angle of a water droplet spreading on it. Therefore, we conclude that this “water wets water” mechanism acting on the photo-adsorbed water layers is responsible for the light-induced superwetting of TiO2. Similar mechanism may be applied for better understanding of the hydrophilic conversion of doped TiO2 or other photo-catalytic oxides. PMID:24711400

  5. Effects of RGD immobilization on light-induced cell sheet detachment from TiO2 nanodots films.

    PubMed

    Cheng, Kui; Wang, Tiantian; Yu, Mengliu; Wan, Hongping; Lin, Jun; Weng, Wenjian; Wang, Huiming

    2016-06-01

    Light-induced cell detachment is reported to be a safe and effective cell sheet harvest method. In the present study, the effects of arginine-glycine-aspartic acid (RGD) immobilization on cell growth, cell sheet construction and cell harvest through light illumination are investigated. RGD was first immobilized on TiO2 nanodots films through simple physical adsorption, and then mouse pre-osteoblastic MC3T3-E1 cells were seeded on the films. It was found that RGD immobilization promoted cell adhesion and proliferation. It was also observed that cells cultured on RGD immobilized films showed relatively high level of pan-cadherin. Cells harvested with ultraviolet illumination (365nm) showed good viability on both RGD immobilized and unmodified TiO2 nanodot films. Single cell detachment assay showed that cells detached more quickly on RGD immobilized TiO2 nanodot films. That could be ascribed to the RGD release after UV365 illumination. The current study demonstrated that RGD immobilization could effectively improve both the cellular responses and light-induced cell harvest. PMID:27040216

  6. Analysis of different strategies adapted by two cassava cultivars in response to drought stress: ensuring survival or continuing growth

    PubMed Central

    Zhao, Pingjuan; Liu, Pei; Shao, Jiaofang; Li, Chunqiang; Wang, Bin; Guo, Xin; Yan, Bin; Xia, Yiji; Peng, Ming

    2015-01-01

    Cassava is one of the most drought-tolerant crops, however, the underlying mechanism for its ability to survive and produce under drought remains obscure. In this study, two cassava cultivars, SC124 and Arg7, were treated by gradually reducing the soil water content. Their responses to the drought stress were examined through their morphological and physiological traits and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. SC124 plants adapted a ‘survival’ mode under mild drought stress as evidenced by early stomatal closure and a reduction in the levels of various photosynthetic proteins and photosynthetic capacity, resulting in early growth quiescence. In contrast, Arg7 plants underwent senescence of older leaves but continued to grow, although at a reduced rate, under mild drought. SC124 plants were more capable of surviving prolonged severe drought than Arg7. The iTRAQ analysis identified over 5000 cassava proteins. Among the drought-responsive proteins identified in the study were an aquaporin, myo-inositol 1-phosphate synthases, and a number of proteins involved in the antioxidant systems and secondary metabolism. Many proteins that might play a role in signalling or gene regulation were also identified as drought-responsive proteins, which included several protein kinases, two 14-3-3 proteins, several RNA-binding proteins and transcription factors, and two histone deacetylases. Our study also supports the notion that linamarin might play a role in nitrogen reallocation in cassava under drought. PMID:25547914

  7. Light-induced reorientation in the purple membrane.

    PubMed Central

    Wan, C; Qian, J; Johnson, C K

    1993-01-01

    Reorientation of bacteriorhodopsin in the native purple membrane was studied by time-resolved linear dichroism spectroscopy (TRLD) over the millisecond time regime. The time responses observed in TRLD are distinctly different from the isotropic transient absorption (TA) at wavelengths in the range 550-590 nm, where the bacteriorhodopsin ground state absorbs. In contrast, the TA and TRLD responses have nearly identical time dependence at 410 and 690 nm, where the intermediates M and O, respectively, principally contribute. These results demonstrate ground-state bacteriorhodopsin reorientation triggered by the photocycle. The TRLD and TA data are analyzed to test models for reorientational motion. Rotational diffusion of ground-state bacteriorhodopsin cannot account for the details of the data. Rather, the results are shown to be consistent with a reversible reorientation of "spectator" (nonexcited) members of the bacteriorhodopsin trimer in the purple membrane in response to the photocycling member of the trimer. This response may be associated with cooperativity in the trimer. PMID:8218916

  8. Vemurafenib in leptomeningeal carcinomatosis from melanoma: a case report of near-complete response and prolonged survival.

    PubMed

    Floudas, Charalampos S; Chandra, Abhinav B; Xu, Yiqing

    2016-06-01

    Targeted therapies such as the BRAF inhibitors vemurafenib and dabrafenib are highly effective in the treatment of systemic metastatic melanoma and have been shown to be effective in controlling solid brain metastases; however, limited data exist on their activity in leptomeningeal spread. Here, we present a case of a 60-year-old woman who developed leptomeningeal carcinomatosis from melanoma after resection and stereotactic radiotherapy of melanoma brain metastases, with poor performance status, who received vemurafenib as first-line treatment, resulting in significant clinical and imaging response as well as prolonged survival. PMID:26974967

  9. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

    PubMed Central

    Mirzayans, Razmik; Andrais, Bonnie; Kumar, Piyush; Murray, David

    2016-01-01

    It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence) in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional “repair and survive, or die” hypothesis. PMID:27187358

  10. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

    PubMed

    Mirzayans, Razmik; Andrais, Bonnie; Kumar, Piyush; Murray, David

    2016-01-01

    It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence) in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E₂, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional "repair and survive, or die" hypothesis. PMID:27187358

  11. Multiple phytochromes are involved in red-light-induced enhancement of first-positive phototropism in Arabidopsis thaliana.

    PubMed Central

    Janoudi, A K; Gordon, W R; Wagner, D; Quail, P; Poff, K L

    1997-01-01

    The amplitude of phototropic curvature to blue light is enhanced by a prior exposure of seedlings to red light. This enhancement is mediated by phytochrome. Fluence-response relationships have been constructed for red-light-induced enhancement in the phytochrome A (phyA) null mutant, the phytochrome B- (phyB) deficient mutant, and in two transgenic lines of Rabidopsis thaliana that overexpress either phyA or phyB. These fluence-response relationships demonstrate the existence of two response in enhancement, a response in the very-low-to-low-fluence range, and a response in the high-fluence range. Only the response in the high-fluence range is present in the phyA null mutant. In contrast, the phyB-deficient mutant is indistinguishable from the wild-type parent in red-light responsiveness. These data indiacate that phyA is necessary for the very-low-to-low but not the high-influence response, and that phyB is not necessary for either response range. Based on these results, the high-fluence response, if controlled by a single phytochrome, must be controlled by aphytochorme other than phyA of phyB. Overexpression of phyA has a negative effect and overexpression of phyB has an enhancing effect in the high-fluence range. These results suggest that overexpression of either phytochrome perturbs the function of the endogenous photoreceptor system in an unpredictable fashion. PMID:9085579

  12. Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from Progressive Light-Induced Retinal Degeneration

    PubMed Central

    Ramchani-Ben Othman, Khaoula; Cercy, Christine; Amri, Mohamed; Doly, Michel; Ranchon-Cole, Isabelle

    2015-01-01

    In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration. PMID:26042773

  13. Light-induced vibration in the hearing organ.

    PubMed

    Ren, Tianying; He, Wenxuan; Li, Yizeng; Grosh, Karl; Fridberger, Anders

    2014-01-01

    The exceptional sensitivity of mammalian hearing organs is attributed to an active process, where force produced by sensory cells boost sound-induced vibrations, making soft sounds audible. This process is thought to be local, with each section of the hearing organ capable of amplifying sound-evoked movement, and nearly instantaneous, since amplification can work for sounds at frequencies up to 100 kHz in some species. To test these fundamental precepts, we developed a method for focally stimulating the living hearing organ with light. Light pulses caused intense and highly damped mechanical responses followed by traveling waves that developed with considerable delay. The delayed response was identical to movements evoked by click-like sounds. This shows that the active process is neither local nor instantaneous, but requires mechanical waves traveling from the cochlear base toward its apex. A physiologically-based mathematical model shows that such waves engage the active process, enhancing hearing sensitivity. PMID:25087606

  14. APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts.

    PubMed

    Hong, Jun; Chen, Zheng; Peng, Dunfa; Zaika, Alexander; Revetta, Frank; Washington, M Kay; Belkhiri, Abbes; El-Rifai, Wael

    2016-03-29

    Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0.01). To mimic in vivo conditions, we treated in vitro cell models with a cocktail of ABS. The knockdown of endogenous APE1 in EAC FLO-1 cells significantly increased oxidative DNA damage (P < 0.01) and DNA single- and double-strand breaks (P < 0.01), whereas overexpression of APE1 in EAC OE33 cells reversed these effects. Annexin V/PI staining indicated that the APE1 expression in OE33 cells protects against ABS-induced apoptosis. In contrast, knockdown of endogenous APE1 in FLO-1 cells increased apoptosis under the same conditions. Mechanistic investigations indicated that the pro-survival function of APE1 was associated with the regulation of stress response c-Jun N-terminal protein kinase (JNK) and p38 kinases. Pharmacological inhibition of APE1 base excision repair (BER) function decreased cell survival and enhanced activation of JNK and p38 kinases by ABS. Our findings suggest that constitutive overexpression of APE1 in EAC may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes. PMID:26934647

  15. APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts

    PubMed Central

    Hong, Jun; Chen, Zheng; Peng, Dunfa; Zaika, Alexander; Revetta, Frank; Washington, M. Kay; Belkhiri, Abbes; El-Rifai, Wael

    2016-01-01

    Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0.01). To mimic in vivo conditions, we treated in vitro cell models with a cocktail of ABS. The knockdown of endogenous APE1 in EAC FLO-1 cells significantly increased oxidative DNA damage (P < 0.01) and DNA single- and double-strand breaks (P < 0.01), whereas overexpression of APE1 in EAC OE33 cells reversed these effects. Annexin V/PI staining indicated that the APE1 expression in OE33 cells protects against ABS-induced apoptosis. In contrast, knockdown of endogenous APE1 in FLO-1 cells increased apoptosis under the same conditions. Mechanistic investigations indicated that the pro-survival function of APE1 was associated with the regulation of stress response c-Jun N-terminal protein kinase (JNK) and p38 kinases. Pharmacological inhibition of APE1 base excision repair (BER) function decreased cell survival and enhanced activation of JNK and p38 kinases by ABS. Our findings suggest that constitutive overexpression of APE1 in EAC may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes. PMID:26934647

  16. Surviving the Acid Test: Responses of Gram-Positive Bacteria to Low pH

    PubMed Central

    Cotter, Paul D.; Hill, Colin

    2003-01-01

    Gram-positive bacteria possess a myriad of acid resistance systems that can help them to overcome the challenge posed by different acidic environments. In this review the most common mechanisms are described: i.e., the use of proton pumps, the protection or repair of macromolecules, cell membrane changes, production of alkali, induction of pathways by transcriptional regulators, alteration of metabolism, and the role of cell density and cell signaling. We also discuss the reponses of Listeria monocytogenes, Rhodococcus, Mycobacterium, Clostridium perfringens, Staphylococcus aureus, Bacillus cereus, oral streptococci, and lactic acid bacteria to acidic environments and outline ways in which this knowledge has been or may be used to either aid or prevent bacterial survival in low-pH environments. PMID:12966143

  17. Survival, reproductive, and growth responses in fish to creosote exposure in aquatic mesocosms

    SciTech Connect

    Munro, K.A.; Solomon, K.R.; Bestari, K.T.; Robinson, R.D.

    1995-12-31

    Creosote is a coal tar distillate, consisting mainly of a mixture of polyaromatic hydrocarbons (PAHs). Its widespread use as a wood preservative presents a potential risk to aquatic ecosystems. The use of mesocosms (precolonized with zooplankton, phytoplankton, macroinvertebrates, and periphyton) enabled evaluation of the total impact of creosote exposure, resulting from both direct toxic effects and indirect community-level interactions. Two methods of creosote addition were used, resulting in two series of mesocosm exposures: sixteen ponds were dosed with liquid creosote (from 0 to 100 ppm), and eight were dosed using creosote impregnated pilings (0 to 6 pilings per pond). In addition to growth and survival in two species of fish, Carassius auratus and Pimephales promelas, a number of reproductive parameters were measured (reproductive hormones, egg production, hatching success, and weight/frequency distribution of juveniles).

  18. Localized light-induced protein dimerization in living cells using a photocaged dimerizer

    PubMed Central

    Ballister, Edward R.; Aonbangkhen, Chanat; Mayo, Alyssa M.; Lampson, Michael A.; Chenoweth, David M.

    2015-01-01

    Regulated protein localization is critical for many cellular processes. Several techniques have been developed for experimental control over protein localization, including chemically induced and light-induced dimerization, which both provide temporal control. Light-induced dimerization offers the distinct advantage of spatial precision within subcellular length scales. A number of elegant systems have been reported that utilize natural light-sensitive proteins to induce dimerization via direct protein–protein binding interactions, but the application of these systems at cellular locations beyond the plasma membrane has been limited. Here we present a new technique to rapidly and reversibly control protein localization in living cells with subcellular spatial resolution using a cell-permeable, photoactivatable chemical inducer of dimerization. We demonstrate light-induced recruitment of a cytosolic protein to individual centromeres, kinetochores, mitochondria and centrosomes in human cells, indicating that our system is widely applicable to many cellular locations. PMID:25400104

  19. Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits.

    PubMed

    Seledtsova, Galina V; Shishkov, Alexey A; Kaschenko, Erika A; Goncharov, Andrey G; Gazatova, Natalya D; Seledtsov, Victor I

    2016-04-01

    New therapies for melanoma have yielded promising results, but their application is limited because of serious side-effects and only moderate impact on patient survival. Vaccine therapies may offer some hope by targeting tumor-specific responses, considering the immunogenic nature of melanomas. To investigate the safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage III melanoma patients and evaluate the survival rate in treated patients. Twenty-seven stage III melanoma patients were immunized with a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells. Neither grade III/IV toxicities, nor clinically significant changes in blood and biochemical parameters were noted after an induction course of 10 XPV subcutaneous immunizations. No laboratory or clinical signs of systemic autoimmunity were documented. Following 10 vaccinations, a relative increase in the numbers of circulating memory CD4+CD45RO+ T cells (but not CD8+ CD45RO+ T cells) was observed. Peripheral blood mononuclear cells obtained from XPV-treated patients demonstrated increased proliferative responses to human BRO melanoma-associated antigens and marked increases in serum levels of IFN-γ and IL-8. Serum levels of TNF-α, IL-4 and IL-6 were not affected. The overall five-year survival rate in the treated patients was significantly higher than that in 27 control patients with matched clinical and prognostic characteristics (55% vs 18%). XPV-based immunotherapy could be maximally effective when started as early as possible before or after surgical excision of the primary tumor and local metastases, i.e. when tumor-mediated suppressive effects on immunity are minimal. PMID:27026566

  20. DNA-PK – a candidate driver of hepatocarcinogenesis and tissue biomarker that predicts response to treatment and survival

    PubMed Central

    Cornell, Liam; Munck, Joanne; Alsinet, Clara; Villanueva, Augusto; Ogle, Laura; Willoughby, Catherine; Televantou, Despina; Thomas, Huw; Jackson, Jennifer; Burt, Alastair; Newell, David; Rose, John; Manas, Derek M; Shapiro, Geoffrey; Curtin, Nicola; Reeves, Helen L

    2014-01-01

    Purpose Therapy resistance and associated liver disease make hepatocellular cancers (HCC) difficult to treat with traditional cytotoxic therapies, while newer targeted approaches offer only modest survival benefit. We focused on DNA-dependent protein kinase, DNA-PKcs, encoded by PRKDC and central to DNA damage repair by non-homologous end joining. Our aim was to explore its roles in hepatocarcinogenesis and as a novel therapeutic candidate. Experimental Design PRKDC was characterised in liver tissues from of 132 patients (normal liver (n=10), cirrhotic liver (n=13), dysplastic nodules (n=18), HCC (n=91)) using Affymetrix U133 Plus 2.0 and 500K Human Mapping SNP arrays (cohort 1). In addition, we studied a case series of 45 patients with HCC undergoing diagnostic biopsy (cohort 2). Histological grading, response to treatment and survival were correlated with DNA-PKcs quantified immunohistochemically. Parallel in vitro studies determined the impact of DNA-PK on DNA repair and response to cytotoxic therapy. Results Increased PRKDC expression in HCC was associated with amplification of its genetic locus in cohort 1. In cohort 2, elevated DNA-PKcs identified patients with treatment-resistant HCC, progressing at a median of 4.5 months compared to 16.9 months, while elevation of activated pDNA-PK independently predicted poorer survival. DNA-PKcs was high in HCC cell lines, where its inhibition with NU7441 potentiated irradiation and doxorubicin-induced cytoxicity, while the combination suppressed HCC growth in vitro and in vivo. Conclusions These data identify PRKDC/DNA-PKcs as a candidate driver of hepatocarcinogenesis, whose biopsy characterisation at diagnosis may impact stratification of current therapies, and whose specific future targeting may overcome resistance. PMID:25480831

  1. Survival response of hippocampal neurons under low oxygen conditions induced by Hippophae rhamnoides is associated with JAK/STAT signaling.

    PubMed

    Manickam, Manimaran; Tulsawani, Rajkumar

    2014-01-01

    Janus activated kinase/signal transducers and activators of transcription (JAK/STATs) pathway are associated with various neuronal functions including cell survival and inflammation. In the present study, it is hypothesized that protective action of aqueous extract of Hippophae rhamnoides in hippocampal neurons against hypoxia is mediated via JAK/STATs. Neuronal cells exposed to hypoxia (0.5% O2) display higher reactive oxygen species with compromised antioxidant status compared to unexposed control cells. Further, these cells had elevated levels of pro-inflammatory cytokines; tumor necrosis factor α and interleukin 6 and nuclear factor κappa B. Moreover, the expression of JAK1 was found to be highly expressed with phosphorylation of STAT3 and STAT5. Cells treated with JAK1, STAT3 and STAT5 specific inhibitors resulted in more cell death compared to hypoxic cells. Treatment of cells with extract prevented oxidative stress and inflammatory response associated with hypoxia. The extract treated cells had more cell survival than hypoxic cells with induction of JAK1 and STAT5b. Cells treated with extract having suppressed JAK1 or STAT3 or STAT5 expression showed reduced cell viability than the cell treated with extract alone. Overall, the findings from these studies indicate that the aqueous extract of Hippophae rhamnoides treatment inhibited hypoxia induced oxidative stress by altering cellular JAK1, STAT3 and STAT5 levels thereby enhancing cellular survival response to hypoxia and provide a basis for possible use of aqueous extract of Hippophae rhamnoides in facilitating tolerance to hypoxia. PMID:24516559

  2. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    SciTech Connect

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  3. Light-induced basilar membrane vibrations in the sensitive cochlea

    NASA Astrophysics Data System (ADS)

    Grosh, Karl; Ren, Tianying; He, Wenxuan; Fridberger, Anders; Li, Yizeng; Nankali, Amir

    2015-12-01

    The exceptional sensitivity of mammalian hearing organ is attributed to an outer hair cell-mediated active process, where forces produced by sensory cells boost sound-induced vibrations, making soft sounds audible. This process is thought to be local, with each section of the hearing organ capable of amplifying sound-evoked movement, and nearly instantaneous, since amplification can work for sounds at frequencies up to 100 kHz in some species. To test these precepts, we developed a method for focally stimulating the living hearing organ with light. Light pulses caused intense and highly damped mechanical responses followed by traveling waves that developed with considerable delay. The delayed response was identical to movements evoked by click-like sounds. A physiologically based mathematical model shows that such waves engage the active process, enhancing hearing sensitivity. The experiments and the theoretical analysis show that the active process is neither local nor instantaneous, but requires mechanical waves traveling from the cochlear base toward its apex.

  4. The Effect of Decitabine Dose Modification and Myelosuppression on Response and Survival in Patients With Myelodysplastic Syndromes

    PubMed Central

    Jabbour, Elias; Garcia-Manero, Guillermo; Cornelison, A. Megan; Cortes, Jorge E.; Ravandi, Farhad; Daver, Naval; Kadia, Tapan; Teng, Angela; Kantarjian, Hagop

    2014-01-01

    Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of 2 decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction, or delay, and death (modification: P = .006, hazard ratio [HR] = 2.04; reduction/delay: P = .011, HR = 2.00; death: P = .003, HR = 1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs 10%; P = .015). Patients with no dose modifications had faster progression to AML versus patients with dose modifications (P = .004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. PMID:24844364

  5. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy.

    PubMed

    Hambrook, Lydia E; Bennett, Peter F

    2012-04-01

    This retrospective study was designed to assess the effect of pimobendan on the median survival time (MST) of cats with non-taurine responsive dilated cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS) <28% and a lack of response to taurine therapy were included over a 9-year period (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan (n=16) treatment groups. All cats received standard treatment with frusemide, taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days) was four times that of the non-pimobendan group (12 days; 1 to 244 days). The difference in survival between the two groups was statistically significant (P = 0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse effects to pimobendan were noted. PMID:22412159

  6. MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis

    SciTech Connect

    Liu Xiangde Nelson, Amy; Wang Xingqi; Kanaji, Nobuhiro; Kim, Miok; Sato, Tadashi; Nakanishi, Masanori; Li Yingji; Sun Jianhong; Michalski, Joel; Patil, Amol; Basma, Hesham; Rennard, Stephen I.

    2009-02-27

    MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-ss1 plus cytomix (a mixture of IL-1ss, IFN-{gamma} and TNF-{alpha}). TGF-ss1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 {+-} 0.6% of control vs 83.1 {+-} 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 {+-} 1.5%, p < 0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.

  7. Hantzsch Ester as a Photosensitizer for the Visible-Light-Induced Debromination of Vicinal Dibromo Compounds.

    PubMed

    Chen, Wenxin; Tao, Huachen; Huang, Wenhao; Wang, Guoqiang; Li, Shuhua; Cheng, Xu; Li, Guigen

    2016-07-01

    The debromination of vicinal dibromo compounds to generate alkenes usually requires harsh reaction conditions and the addition of catalysts. Just recently the visible-light-induced debromination of vicinal dibromo compounds emerged as a possible alternative to commonly used methods, but the substrate scope of this reaction is limited and a photocatalyst is necessary for the successful conversion of the starting compounds. A catalyst-free visible-light-induced debromination of vicinal dibromo compounds with a base-activated Hantzsch ester as photosensitizer is reported. The method has a wide substrate scope and a broad functional-group compatibility. PMID:27128783

  8. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    PubMed

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales. PMID:25527297

  9. T-Cell Responses Are Associated with Survival in Acute Melioidosis Patients

    PubMed Central

    Jenjaroen, Kemajittra; Chumseng, Suchintana; Sumonwiriya, Manutsanun; Ariyaprasert, Pitchayanant; Chantratita, Narisara; Sunyakumthorn, Piyanate; Hongsuwan, Maliwan; Wuthiekanun, Vanaporn; Fletcher, Helen A.; Teparrukkul, Prapit; Limmathurotsakul, Direk; Day, Nicholas P. J.; Dunachie, Susanna J.

    2015-01-01

    Background Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design. Methods We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-γ) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43). Results We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN-γ cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-γ cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/μl. Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2–13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes. Conclusions The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such

  10. Chronic exposure to environmentally-relevant concentrations of fluoxetine (Prozac) decreases survival, increases abnormal behaviors, and delays predator escape responses in guppies.

    PubMed

    Pelli, Marco; Connaughton, Victoria P

    2015-11-01

    This study evaluates the impact of fluoxetine, an antidepressant drug and common pollutant in aquatic environments, on growth, survival, and behavior in juvenile guppies and on predator escape responses in adult guppies (Poecilia reticulata). In juveniles, the effects of acute (4d) and chronic (35d) exposure on growth and survival were examined, and behavioral changes were noted throughout the chronic experiment. In adults, escape responses to a mock predator during chronic (28d) fluoxetine exposure were videotaped to determine the overall speed of response in treated vs. control fish. The effects of fish gender and the presence of a group/school on escape responses were also determined. Our results show that acute exposure to nominal concentrations of 0.03 and 0.5μg/L, levels within the environment, did not adversely impact juvenile guppy survival. However, chronic exposure significantly reduced weight, length, and belly width/girth measurements compared to controls. Chronic exposure also resulted in abnormal swimming behavior and reduced survival in juveniles. In adults, fluoxetine exposure significantly delayed predator escape responses in both males and females. Escape responses were also reduced when adults were tested either individually or in a group, with significantly more delayed responses seen in individually tested fish. Taken together, these findings suggest that fluoxetine can impact guppy populations, during both juvenile and adult stages, with chronic exposure resulting in decreased survival and growth and altered behavioral responses. PMID:26126230

  11. Relationship between 3-Methyl-2,4-nonanedione Concentration and Intensity of Light-induced Off-odor in Soy Bean Oil.

    PubMed

    Sano, Takashi; Iwahashi, Maiko; Imagi, Jun; Sato, Toshiro; Yamashita, Toshiyuki; Fukusaki, Eiichiro; Bamba, Takeshi

    2016-05-01

    A beany and green off-odor is developed in soy bean oil (SBO) under light-induced oxidative conditions. 3-Methyl-2,4-nonanedione (3-MND) was inferred as the compound responsible for the off-odor. In this study, we designed a simple quantification method for 3-MND in SBO, and evaluated the relationship between the 3-MND concentration and the intensity of the off-odor. 3-MND was analyzed by GC/MS with a thermal desorption unit system. By our method, the 3-MND concentration was found to increase with storage days and the SBO content under light exposure, and there was a high correlation between the measured 3-MND concentration and the intensity of the light-induced off-odor in SBO (R = 0.9586). PMID:27086994

  12. Expression and Immune Responses to MAGE Antigens Predict Survival in Epithelial Ovarian Cancer

    PubMed Central

    Daudi, Sayeema; Eng, Kevin H.; Mhawech-Fauceglia, Paulette; Morrison, Carl; Miliotto, Anthony; Beck, Amy; Matsuzaki, Junko; Tsuji, Takemasa; Groman, Adrienne; Gnjatic, Sacha; Spagnoli, Guillo; Lele, Shashikant; Odunsi, Kunle

    2014-01-01

    The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:–A4, MAGE-A1:–C1 and MAGE-A4:–A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01–2.04, p = 0.044 and OR 1.3, CI 1.03–1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42–0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients. PMID:25101620

  13. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  14. Predicting Response to Hormonal Therapy and Survival in Men with Hormone Sensitive Metastatic Prostate Cancer

    PubMed Central

    Grivas, Petros D.; Robins, Diane M.; Hussain, Maha

    2014-01-01

    Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date. There is significant heterogeneity in the depth and duration of hormonal response and in the natural history of advanced disease; therefore to better optimize/individualize therapy and for future development, identification of biomarkers is critical. This review summarizes the current data on the role of several candidate biomarkers that have been evaluated in the advanced/metastatic disease setting. PMID:22705096

  15. Examining sexual assault survival of adult women: responses, mediators, and current theories.

    PubMed

    Hellman, Ann

    2014-01-01

    The purpose of this article is to examine the state of the science of sexual assault research to direct future research in three key areas: responses, mediators, and current theory with a religious or spiritual focus addressing recovery. Three research questions guided the investigation of literature and the formation of this article: (a) What are common survivor responses to, and long-term effects of, sexual assault?; (b) What are mediators for recovery after sexual assault?; and (c) What theory with a religious or spiritual focus exists to address recovery from sexual assault? This research identifies significant gaps in the literature underscoring the importance of future research that examines responses to and long-term effects of sexual assault, need for mediators during recovery, and need to develop theory using religious and spiritual tenets aiding in recovery from sexual assault. Further research is necessary to develop this science, expand understanding, and support sexual assault survivors on their recovery journey. PMID:25144589

  16. Compartmentalized expression of light-induced clock genes in the suprachiasmatic nucleus of the diurnal grass rat (Arvicanthis niloticus)

    PubMed Central

    Ramanathan, Chidambaram; Campbell, Amy; Tomczak, Ashley; Nunez, Antonio A.; Smale, Laura; Yan, Lily

    2009-01-01

    Photic responses of the circadian system are mediated through light-induced clock gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents, depending on the timing of light exposure, Per1 and Per2 gene expression shows distinct compartmentalized patterns that correspond to the behavioral responses. Whether the gene-and region-specific induction patterns are unique to nocturnal animals, or are also present in diurnal species is unknown. We explored this question by examining the light-induced Per1 and Per2 gene expression in functionally distinct SCN sub regions, using diurnal grass rats Arvicanthis niloticus. Light exposure during nighttime induced Per1 and Per2 expression in the SCN, showing unique spatiotemporal profiles depending on the phase of the light exposure. After a phase delaying light pulse (LP) in the early night, strong Per1 induction was observed in the retinorecipient core region of the SCN, while strong Per2 induction was observed throughout the entire SCN. After a phase advancing LP in the late night, Per1 was first induced in the core and then extended into the whole SCN, accompanied by a weak Per2 induction. This compartmentalized expression pattern is very similar to that observed in nocturnal rodents, suggesting that the same molecular and intercellular pathways underlying acute photic responses are present in both diurnal and nocturnal species. However, after a LP in early subjective day, which induces phase advances in diurnal grass rats, but not in nocturnal rodents, we did not observe any Per1 or Per2 induction in the SCN. This result suggests that in spite of remarkable similarities in the SCN of diurnal and nocturnal rodents, unique mechanisms are involved in mediating the phase shifts of diurnal animals during the subjective day. PMID:19393297

  17. Transcriptomic response of Listeria monocytogenes during the transition to the long-term-survival phase.

    PubMed

    Wen, Jia; Deng, Xiangyu; Li, Zengxin; Dudley, Edward G; Anantheswaran, Ramaswamy C; Knabel, Stephen J; Zhang, Wei

    2011-09-01

    Listeria monocytogenes can change its cellular morphology from bacilli to cocci during the transition to the long-term-survival (LTS) phase. The LTS cells demonstrated increased baro- and thermotolerance compared to their vegetative counterparts. So far, the underlying mechanisms that trigger this morphological and physiological transition remain largely unknown. In this study, we compared the transcriptomic profiles of L. monocytogenes serotype 4b strain F2365 at different growth stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome DNA chip approach. We identified a total of 225 differentially expressed genes (≥4-fold; P < 0.05) during the transition to the LTS phase in TSBYE. Genes related to cell envelope structure, energy metabolism, and transport were most significantly upregulated in the LTS phase. The upregulation of compatible solute transporters may lead to the accumulation of cellular solutes, lowering intracellular water activity and thus increasing bacterial stress resistance during the transition to the LTS phase. The downregulation of genes associated with protein synthesis may indicate a status of metabolic dormancy of the LTS cells. The transcriptomic profiles of resuscitated LTS cells in fresh TSBYE resembled those of log-phase cells (r=0.94), as the LTS cells rapidly resume metabolic activities and transit back to log phase with decreased baro- and thermotolerance. PMID:21764970

  18. Increase of the behavioral response to kairomones by the parasitoid wasp Leptopilina heterotoma surviving insecticides.

    PubMed

    Delpuech, J M; Bardon, C; Boulétreau, M

    2005-08-01

    Hymenopterous parasitoids are key species involved in the regulation of insect populations. Kairomone perception is an important step leading to host parasitization. The massive use of insecticides induces environmental pollution that can interact with the reproduction of parasitoids. In this work, we have determined the sublethal effects of two insecticides, an organophosphorus (chlorpyrifos) and a pyrethroid (deltamethrin), on the arrestment, by host kairomones, of female parasitoids surviving an LD 20 for 24 h. The behavior of the parasitoids has been recorded with a video-computerized system. The analysis of the behaviors in control conditions versus exposed to an LD 20 have shown that both insecticides significantly increased the arrestment of parasitoids by kairomones. This increase was not followed up by a modification of the kinetics of the behavior. In both control and exposed conditions, parasitoids regularly increased their residence time on the kairomone patch indicating that no saturation to kairomones had occurred. In a field situation where hosts could be scarce, this increase in arrestment could be advantageous for parasitoids by increasing their host finding. PMID:16082580

  19. TEMOZOLOMIDE FOR RECURRENT INTRACRANIAL EPENDYMOMA OF THE ADULT: PATTERNS OF RESPONSE, SURVIVAL AND CORRELATIONS WITH MGMT PROMOTER METHYLATION

    PubMed Central

    Soffietti, Riccardo; Bosa, Chiara; Bertero, Luca; Trevisan, Elisa; Cassoni, Paola; Morra, Isabella; Rudà, Roberta

    2014-01-01

    years), and 4/18 (22%) patients are alive. MGMT analysis was available in 10 patients, of whom 6 were unmethylated and 4 methylated. There were no correlations between MGMT methylation and response to TMZ or survival. CONCLUSIONS: Temozolomide has activity in recurrent ependymomas, regardless of tumor grade. Responses are often delayed and prevail in chemo-naive patients. MGMT promoter methylation does not influence neither response nor survival. SECONDARY CATEGORY: n/a.

  20. Light-induced electronic non-equilibrium in plasmonic particles.

    PubMed

    Kornbluth, Mordechai; Nitzan, Abraham; Seideman, Tamar

    2013-05-01

    We consider the transient non-equilibrium electronic distribution that is created in a metal nanoparticle upon plasmon excitation. Following light absorption, the created plasmons decohere within a few femtoseconds, producing uncorrelated electron-hole pairs. The corresponding non-thermal electronic distribution evolves in response to the photo-exciting pulse and to subsequent relaxation processes. First, on the femtosecond timescale, the electronic subsystem relaxes to a Fermi-Dirac distribution characterized by an electronic temperature. Next, within picoseconds, thermalization with the underlying lattice phonons leads to a hot particle in internal equilibrium that subsequently equilibrates with the environment. Here we focus on the early stage of this multistep relaxation process, and on the properties of the ensuing non-equilibrium electronic distribution. We consider the form of this distribution as derived from the balance between the optical absorption and the subsequent relaxation processes, and discuss its implication for (a) heating of illuminated plasmonic particles, (b) the possibility to optically induce current in junctions, and (c) the prospect for experimental observation of such light-driven transport phenomena. PMID:23656152

  1. Transcriptional responses to fluctuating thermal regimes underpinning differences in survival in the solitary bee Megachile rotundata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transcriptional responses of insects to long-term, ecologically relevant temperature stress are poorly understood. Long-term exposure to low temperatures, commonly referred to as chilling, can lead to physiological effects collectively known as chill injury. Periodically increasing temperatures ...

  2. Immune Response of Mormon Crickets that Survived Infection by Beauveria Bassiana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beauveria bassiana is an entomopathogenic Ascomycete fungus that serves as a biological control agent of Mormon crickets (Anabrus simplex Haldeman) and other grasshopper pests. To measure the dose dependent response of Mormon crickets to fungal attack, we applied B. bassiana strain GHA topically to...

  3. Light-induced bonding and debonding with supramolecular adhesives.

    PubMed

    Heinzmann, Christian; Coulibaly, Souleymane; Roulin, Anita; Fiore, Gina L; Weder, Christoph

    2014-04-01

    Light-responsive supramolecular polymers were applied as reversible adhesives that permit bonding and debonding on demand features. A telechelic poly(ethylene-co-butylene) (PEB) was functionalized with either self-complementary hydrogen-bonding ureidopyrimidinone (UPy) motifs (UPy-PEB-UPy) or 2,6-bis(1'-methylbenzimidazolyl)-pyridine (Mebip) ligands (Mebip-PEB-Mebip), which can coordinate to metal ions (Zn(NTf2)2) and form a metallosupramolecular polymer with the sum formula [Znx(Mebip-PEB-Mebip)](NTf2)2x, with x ≈ 1. In the latter case, light-heat conversion is facilitated by the ultraviolet (UV) light-absorbing metal-ligand motifs, while in the case of UPy-PEB-UPy a UV absorber was added for this purpose. Single lap joints were prepared by sandwiching films of the supramolecular polymers of a thickness of 80-100 μm between two glass, quartz, or stainless steel substrates and bonded by exposure to either UV light (320-390 nm, 900 mW/cm(2)) or heat (80 or 200 °C for UPy-PEB-UPy and the metallopolymer, respectively). UPy-PEB-UPy and [Zn0.8Mebip-PEB-Mebip](NTf2)1.6 displayed a shear strength of 0.9-1.2 and 1.8-2.5 MPa, respectively. When lap joints were placed under load and exposed to light or heat, the samples debonded within seconds. They could be rebonded through exposure to light or heat, and the original adhesive properties were recovered. PMID:24484360

  4. Light-induced inhibition of laccase in Pycnoporus sanguineus.

    PubMed

    Hernández, Christian A; Perroni, Yareni; Pérez, José Antonio García; Rivera, Beatriz Gutiérrez; Alarcón, Enrique

    2016-03-01

    The aim was to determine which specific regions of the visible light spectrum were responsible for the induction or inhibition of laccase in Pycnoporus sanguineus. Cultures were exposed to various bandwidth lights: blue (460 nm), green (525 nm), white (a combination of 460 and 560 nm), red (660 nm), and darkness. The results indicate that short wavelengths strongly inhibit the production of laccase: green (3.76 ± 1.12 U/L), blue (1.94 ± 0.36 U/L), and white (1.05 ± 0.21 U/L) in proportions of 85.8, 92.6, and 96.0%, respectively; whereas long wavelengths inhibit laccase production only partially i.e., red light (14.05 ± 4.79 U/L) in a proportion of 46.8%. Maximum activity was induced in absence of visible light (30 °C, darkness), i.e., 30.76 ± 4.0 U/L. It is concluded that the production of laccase in P. sanguineus responds to light stimuli [measured as wavelengths and lx] and that it does so inversely. This can be explained as an ecological mechanism of environmental recognition, given that P. sanguineus develops inside lignocellulose structures in conditions of darkness. The presence of short wavelength light (460-510 nm) would indicate that the organism finds itself in an external environment, unprovided of lignin, and that it is therefore unnecessary to secrete laccase. This possible new regulation in the laccase production in P. sanguineus has important biotechnological implications, for it would be possible to control the production of laccase using light stimuli. PMID:26233233

  5. Conjunctivally Applied BDNF Protects Photoreceptors from Light-Induced Damage

    PubMed Central

    Cerri, Elisa; Origlia, Nicola; Falsini, Benedetto; Barloscio, Davide; Fabiani, Carlotta; Sansò, Marco; Ottino, Sara; Giovannini, Luca; Domenici, Luciano

    2015-01-01

    Purpose To test whether the topical eye treatment with BDNF prevents the effects of continuous light exposure (LE) in the albino rat retina. Methods Two groups of albino rats were used. The first group of rats received an intraocular injection of BDNF (2 μL, 1 μg/μL) before LE, while the second group was treated with one single drop of BDNF (10 μL, 12 μg/μL) dissolved in different types of solutions (physiological solution, the polysaccharide fraction of Tamarind gum, TSP, and sodium carboxy methyl cellulose), at the level of conjunctival fornix before LE. The level of BDNF in the retina and optic nerve was determined by enzyme-linked immunosorbent assay. We recorded the flash electroretinogram (fERG) in dark adapted rats 1 week after LE. At the end of the recording session, the retinas were removed and labeled so that the number of photoreceptors nuclear rows and thickness of the outer nuclear layer was analyzed. Results Intravitreal injection of BDNF before LE prevented fERG impairment. Different ophthalmic preparations were used for topical eye application; the TSP resulted the most suitable vehicle to increase BDNF level in the retina and optic nerve. Topical eye application with BDNF/TSP before LE partially preserved both fERG response and photoreceptors. Conclusions Topical eye treatment with BDNF represents a suitable, noninvasive tool to increase the retinal content of BDNF up to a level capable of exerting neuroprotection toward photoreceptors injured by prolonged LE. Translational Relevance A collyrium containing BDNF may serve as an effective, clinically translational treatment against retinal degeneration. PMID:27190697

  6. MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.

    PubMed

    Tuominen, Rainer; Jewell, Rosalyn; van den Oord, Joost J; Wolter, Pascal; Stierner, Ulrika; Lindholm, Christer; Hertzman Johansson, Carolina; Lindén, Diana; Johansson, Hemming; Frostvik Stolt, Marianne; Walker, Christy; Snowden, Helen; Newton-Bishop, Julia; Hansson, Johan; Egyházi Brage, Suzanne

    2015-06-15

    To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p < 0.005). DTIC/TMZ therapy response rate was found to be significantly associated with MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma. PMID:25400033

  7. The Hypoxia-Inducible Factor 1/NOR-1 Axis Regulates the Survival Response of Endothelial Cells to Hypoxia▿

    PubMed Central

    Martorell, Lluis; Gentile, Maurizio; Rius, Jordi; Rodríguez, Cristina; Crespo, Javier; Badimon, Lina; Martínez-González, José

    2009-01-01

    Hypoxia induces apoptosis but also triggers adaptive mechanisms to ensure cell survival. Here we show that the prosurvival effects of hypoxia-inducible factor 1 (HIF-1) in endothelial cells are mediated by neuron-derived orphan receptor 1 (NOR-1). The overexpression of NOR-1 decreased the rate of endothelial cells undergoing apoptosis in cultures exposed to hypoxia, while the inhibition of NOR-1 increased cell apoptosis. Hypoxia upregulated NOR-1 mRNA levels in a time- and dose-dependent manner. Blocking antibodies against VEGF or SU5614 (a VEGF receptor 2 inhibitor) did not prevent hypoxia-induced NOR-1 expression, suggesting that NOR-1 is not induced by the autocrine secretion of VEGF in response to hypoxia. The reduction of HIF-1α protein levels by small interfering RNAs, or by inhibitors of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway or mTOR, significantly counteracted hypoxia-induced NOR-1 upregulation. Intracellular Ca2+ was involved in hypoxia-induced PI3K/Akt activation and in the downstream NOR-1 upregulation. A hypoxia response element mediated the transcriptional activation of NOR-1 induced by hypoxia as we show by transient transfection and chromatin immunoprecipitation assays. Finally, the attenuation of NOR-1 expression reduced both basal and hypoxia-induced cIAP2 (cellular inhibitor of apoptosis protein 2) mRNA levels, while NOR-1 overexpression upregulated cIAP2. Therefore, NOR-1 is a downstream effector of HIF-1 signaling involved in the survival response of endothelial cells to hypoxia. PMID:19720740

  8. Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival.

    PubMed

    Hain, Karolina O; Colin, Didier J; Rastogi, Shubhra; Allan, Lindsey A; Clarke, Paul R

    2016-01-01

    A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. PMID:27230693

  9. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival

    PubMed Central

    Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta

    2016-01-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis. Streptococcus pneumoniae is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  10. Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

    PubMed Central

    Hain, Karolina O.; Colin, Didier J.; Rastogi, Shubhra; Allan, Lindsey A.; Clarke, Paul R.

    2016-01-01

    A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. PMID:27230693

  11. Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival.

    PubMed

    Jonczyk, Magda S; Escudero, Laura; Sylvius, Nicolas; Norman, Martin; Henriques-Normark, Birgitta; Andrew, Peter W

    2016-04-01

    Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis.Streptococcus pneumonia is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections. PMID:26787718

  12. Light-Induced Alterations in Striatal Neurochemical Profiles

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.

    1997-01-01

    that receives a number of dopaminergic and glutamatergic input and is known to be involved in the modulation of locomotor and behavioral responses.

  13. Non-coherent visible and infrared radiation increase survival to UV (254 nm) in Escherichia coli K12.

    PubMed

    Lage, C; Teixeira, P C; Leitão, A C

    2000-02-01

    Interactions between visible or infrared (IR) and ultraviolet (UV, 254 nm) radiation have been studied in E. coli. Pre-illumination with non-coherent monochromatic 446, 466, 570 and 685 nm radiation, as well as with polychromatic red and IR radiation at room temperature, leads to increased cell survival after a subsequent irradiation with UV light. In the thermic range of the spectrum (red and IR), IR but not red light pre-treatment is able to increase cell survival to a subsequent lethal heat (51 degrees C) challenge, suggesting that increased UV survival may be due to IR-induced heat-shock response. On the other hand, visible-light-induced resistance may be due to a different mechanism, possibly involved with unknown bacterial light receptors. PMID:10836546

  14. Light Induced C-C Coupling of 2-Chlorobenzazoles with Carbamates, Alcohols, and Ethers.

    PubMed

    Lipp, Alexander; Lahm, Günther; Opatz, Till

    2016-06-01

    A light induced, transition-metal-free C-C coupling reaction of 2-chlorobenzazoles with aliphatic carbamates, alcohols, and ethers is presented. Inexpensive reagents, namely sodium acetate, benzophenone, water, and acetonitrile, are employed in a simple reaction protocol using a cheap and widely available 25 W energy saving UV-A lamp at ambient temperature. PMID:27128627

  15. Light-induced resistive switching in silicon-based metal-insulator-semiconductor structures

    NASA Astrophysics Data System (ADS)

    Tikhov, S. V.; Gorshkov, O. N.; Koryazhkina, M. N.; Antonov, I. N.; Kasatkin, A. P.

    2016-05-01

    We have studied light-induced resistive switching in metal-insulator-semiconductor structures based on silicon covered with a tunneling-thin SiO2 layer and nanometer-thick layer of antimony. The role of an insulator was played by yttria-stabilized zirconia.

  16. Structural specifics of light-induced metastable states in copper(II)-nitroxide molecular magnets.

    PubMed

    Barskaya, I Yu; Veber, S L; Fokin, S V; Tretyakov, E V; Bagryanskaya, E G; Ovcharenko, V I; Fedin, M V

    2015-12-28

    Although light-induced magnetostructural switching in copper(II)-nitroxide molecular magnets Cu(hfac)2L(R) has been known for several years, structural characterization of metastable photoinduced states has not yet been accomplished due to significant technical demands. In this work we apply, for the first time, variable-temperature FTIR spectroscopy with photoexcitation to investigate the structural specifics of light-induced states in the Cu(hfac)2L(R) family represented by (i) Cu(hfac)2L(Me) comprising two-spin copper(II)-nitroxide clusters, and (ii) Cu(hfac)2L(Pr) comprising three-spin nitroxide-copper(II)-nitroxide clusters. The light-induced state of Cu(hfac)2L(Me) manifests the same set of vibrational bands as the corresponding thermally-induced state, implying their similar structures. For the second compound Cu(hfac)2L(Pr), the coordination environment of copper(II) is similar in light- and thermally-induced states, but distinct differences are found for packing of the peripheral n-propyl substituent of nitroxide. Thus, generally the structures of the corresponding thermally- and light-induced states in molecular magnets Cu(hfac)2L(R) might differ, and FTIR spectroscopy provides a useful approach for revealing and elucidating such differences. PMID:26571045

  17. TLR9 Activation Dampens the Early Inflammatory Response to Paracoccidioides brasiliensis, Impacting Host Survival

    PubMed Central

    Menino, João Filipe; Saraiva, Margarida; Gomes-Alves, Ana G.; Lobo-Silva, Diogo; Sturme, Mark; Gomes-Rezende, Jéssica; Saraiva, Ana Laura; Goldman, Gustavo H.; Cunha, Cristina; Carvalho, Agostinho; Romani, Luigina; Pedrosa, Jorge; Castro, António Gil; Rodrigues, Fernando

    2013-01-01

    Background Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear. Methodology/Principal findings We used in vitro and in vivo models of infection by P. brasiliensis, comparing wild type and TLR9 deficient (−/−) mice, to assess the contribution of TLR9 on cytokine induction, phagocytosis and outcome of infection. We show that TLR9 recognizes either the yeast form or DNA from P. brasiliensis by stimulating the expression/production of pro-inflammatory cytokines by bone marrow derived macrophages, also increasing their phagocytic ability. We further show that TLR9 plays a protective role early after intravenous infection with P. brasiliensis, as infected TLR9−/− mice died at higher rate during the first 48 hours post infection than wild type mice. Moreover, TLR9−/− mice presented tissue damage and increased expression of several cytokines, such as TNF-α and IL-6. The increased pattern of cytokine expression was also observed during intraperitoneal infection of TLR9−/− mice, with enhanced recruitment of neutrophils. The phenotype of TLR9−/− hosts observed during the early stages of P. brasiliensis infection was reverted upon a transient, 48 hours post-infection, neutrophil depletion. Conclusions/Significance Our results suggest that TLR9 activation plays an early protective role against P. brasiliensis, by avoiding a deregulated type of inflammatory response associated to neutrophils that may lead to tissue damage. Thus

  18. The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications

    PubMed Central

    Kenny, John G.; Ward, Deborah; Josefsson, Elisabet; Jonsson, Ing-Marie; Hinds, Jason; Rees, Huw H.; Lindsay, Jodi A.; Tarkowski, Andrej; Horsburgh, Malcolm J.

    2009-01-01

    Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed

  19. The isolation and identification of a light-induced protein in alfalfa sprouts and the cloning of its specific promoter.

    PubMed

    Su, Xin; Xu, Wei-Zhuo; Liu, Xin; Zhuo, Rui-Fang; Wang, Cai-Yun; Zhang, Xin; Kakutani, K; You, Song

    2013-05-15

    We used 2D-PAGE to isolate a light-induced protein (AL-A) that is expressed abundantly in light-growth alfalfa sprouts. The seven amino acids of the N-terminal region of the protein were identified, and we searched for the protein in GenBank using the BLAST program. The results of the homology analysis showed that the amino acid sequence of the isolated protein is most similar to one from a pea plastocyanin. To identify the protein, we amplified and sequenced the DNA fragment encoding AL-A from genomic alfalfa DNA. We found that the AL-A gene was highly homologous (90%) to the sequences from the pea plastocyanin via multiple alignments, and the deduced protein precursor was predicted to be chloroplast-specific via the ChloroP computer program. The protein was named alfalfa-plastocyanin (AL-P). It was characterized as being a light-inducible protein, and RT-PCR analysis showed that AL-P mRNA transcription only occurred in the leaves of the alfalfa plant and the alfalfa seedlings growth in lighted conditions. PCR was also used to amplify the DNA fragment encoding the AL-P promoter (AL-Pp) from genomic alfalfa DNA. PlantCARE analysis of the promoter sequence indicated that both a typical TATA box and a CAAT box were located in the promoter sequence, and some of the cis-elements that are responsible for light responsiveness were also identified within this promoter region. The AL-P gene promoter fused to the β-glucuronidase (GUS) reporter gene has been examined for expression in transgenic alfalfa seedlings. Our findings have a potential application in plant genetic engineering; the AL-Pp may be used to drive the expression of heterologous genes in transgenic alfalfa plants. PMID:23454621

  20. Overexpression of plasma membrane H+-ATPase in guard cells promotes light-induced stomatal opening and enhances plant growth

    PubMed Central

    Wang, Yin; Noguchi, Ko; Ono, Natsuko; Inoue, Shin-ichiro; Terashima, Ichiro; Kinoshita, Toshinori

    2014-01-01

    Stomatal pores surrounded by a pair of guard cells in the plant epidermis control gas exchange between plants and the atmosphere in response to light, CO2, and the plant hormone abscisic acid. Light-induced stomatal opening is mediated by at least three key components: the blue light receptor phototropin (phot1 and phot2), plasma membrane H+-ATPase, and plasma membrane inward-rectifying K+ channels. Very few attempts have been made to enhance stomatal opening with the goal of increasing photosynthesis and plant growth, even though stomatal resistance is thought to be the major limiting factor for CO2 uptake by plants. Here, we show that transgenic Arabidopsis plants overexpressing H+-ATPase using the strong guard cell promoter GC1 showed enhanced light-induced stomatal opening, photosynthesis, and plant growth. The transgenic plants produced larger and increased numbers of rosette leaves, with ∼42–63% greater fresh and dry weights than the wild type in the first 25 d of growth. The dry weights of total flowering stems of 45-d-old transgenic plants, including seeds, siliques, and flowers, were ∼36–41% greater than those of the wild type. In addition, stomata in the transgenic plants closed normally in response to darkness and abscisic acid. In contrast, the overexpression of phototropin or inward-rectifying K+ channels in guard cells had no effect on these phenotypes. These results demonstrate that stomatal aperture is a limiting factor in photosynthesis and plant growth, and that manipulation of stomatal opening by overexpressing H+-ATPase in guard cells is useful for the promotion of plant growth. PMID:24367097

  1. Overexpression of plasma membrane H+-ATPase in guard cells promotes light-induced stomatal opening and enhances plant growth.

    PubMed

    Wang, Yin; Noguchi, Ko; Ono, Natsuko; Inoue, Shin-ichiro; Terashima, Ichiro; Kinoshita, Toshinori

    2014-01-01

    Stomatal pores surrounded by a pair of guard cells in the plant epidermis control gas exchange between plants and the atmosphere in response to light, CO2, and the plant hormone abscisic acid. Light-induced stomatal opening is mediated by at least three key components: the blue light receptor phototropin (phot1 and phot2), plasma membrane H(+)-ATPase, and plasma membrane inward-rectifying K(+) channels. Very few attempts have been made to enhance stomatal opening with the goal of increasing photosynthesis and plant growth, even though stomatal resistance is thought to be the major limiting factor for CO2 uptake by plants. Here, we show that transgenic Arabidopsis plants overexpressing H(+)-ATPase using the strong guard cell promoter GC1 showed enhanced light-induced stomatal opening, photosynthesis, and plant growth. The transgenic plants produced larger and increased numbers of rosette leaves, with ∼42-63% greater fresh and dry weights than the wild type in the first 25 d of growth. The dry weights of total flowering stems of 45-d-old transgenic plants, including seeds, siliques, and flowers, were ∼36-41% greater than those of the wild type. In addition, stomata in the transgenic plants closed normally in response to darkness and abscisic acid. In contrast, the overexpression of phototropin or inward-rectifying K(+) channels in guard cells had no effect on these phenotypes. These results demonstrate that stomatal aperture is a limiting factor in photosynthesis and plant growth, and that manipulation of stomatal opening by overexpressing H(+)-ATPase in guard cells is useful for the promotion of plant growth. PMID:24367097

  2. Hemolin triggers cell survival on fibroblasts in response to serum deprivation by inhibition of apoptosis.

    PubMed

    Bosch, Rosemary Viola; Alvarez-Flores, Miryam Paola; Maria, Durvanei Augusto; Chudzinski-Tavassi, Ana Marisa

    2016-08-01

    Fibroblasts are the main cellular component of connective tissues and play important roles in health and disease through the production of collagen, fibronectin and growth factors. Under certain conditions, such as wound healing, fibroblasts intensify their metabolic demand, while the restriction of nutrients affect matrix composition, cell metabolism and behavior. In lepidopterans, wound healing is regulated by ecdysteroid hormones, which upregulate multifunctional proteins such as hemolin. However, the role of hemolin in cell proliferation and wound healing is not clear. rLosac is a recombinant hemolin from the caterpillar Lonomia obliqua whose proliferative and cytoprotective effects on endothelial cells have been described. Here, we show that rLosac induces a marked cell survival effect on fibroblast submitted to serum deprivation, which is observable as early as 24h, as demonstrated through the MTT assay, as well as an increase in migration of human dermal fibroblasts (HDF). No effects on cell proliferation or cell cycle distribution of fibroblasts in normal conditions were observed, suggesting that rLosac induces an effect in stressful conditions such serum deprivation but not when nutrient are sufficient. By flow cytometry, rLosac caused an apparent dose-dependent increase in cells in the S phase of the cell cycle and a significant reduction of cells with fragmented DNA. Furthermore, treatment with rLosac results in a significant decrease in the production of reactive oxygen species and in the loss of mitochondrial membrane potential, indicating that a reduction in oxidative stress is involved in rLosac-mediated cytoprotection. Our results also show an up-regulation of Bcl-2 and a down-regulation of Bax protein levels, inhibition of cytochrome c release and a reduction in caspase-3 levels, all considered critical factors for apoptosis. Moreover, rLosac treatment reduces the morphological changes induced by prolonged serum deprivation including the emergence

  3. HGFL supports mammary tumorigenesis by enhancing tumor cell intrinsic survival and influencing macrophage and T-cell responses

    PubMed Central

    Benight, Nancy M.; Wagh, Purnima K.; Zinser, Glendon M.; Peace, Belinda E.; Stuart, William D.; Vasiliauskas, Juozas; Pathrose, Peterson; Starnes, Sandra L.; Waltz, Susan E.

    2015-01-01

    The Ron receptor is overexpressed in human breast cancers and is associated with heightened metastasis and poor survival. Ron overexpression in the mammary epithelium of mice is sufficient to induce aggressive mammary tumors with a high degree of metastasis. Despite the well-documented role of Ron in breast cancer, few studies have examined the necessity of the endogenous Ron ligand, hepatocyte growth factor-like protein (HGFL) in mammary tumorigenesis. Herein, mammary tumor growth and metastasis were examined in mice overexpressing Ron in the mammary epithelium with or without HGFL. HGFL ablation decreased oncogenic Ron activation and delayed mammary tumor initiation. HGFL was important for tumor cell proliferation and survival. HGFL loss resulted in increased numbers of macrophages and T-cells within the tumor. T-cell proliferation and cytotoxicity dramatically increased in HGFL deficient mice. Biochemical analysis of HGFL proficient tumors showed increased local HGFL production, with HGFL loss decreasing β-catenin expression and NF-κB activation. Re-expression of HGFL in HGFL deficient tumor cells stimulated cell migration and invasion with coordinate activation of NF-κB and reduced apoptosis. Together, these results demonstrate critical in vivo functions for HGFL in promoting breast tumorigenesis and suggest that targeting HGFL may inhibit tumor growth and reactivate anti-tumor immune responses. PMID:25938541

  4. Clinical Factors Associated with Response or Survival after Chemotherapy in Patients with Waldenström Macroglobulinemia in Korea

    PubMed Central

    Kim, Kihyun; Yoon, Dok Hyun; Kim, Jin Seok; Eom, Hyeon Seok; Kim, Inho; Lee, Won Sik; Kim, Se Hyung; Lee, Mark Hong; Lee, Jae Hoon; Shin, Ho-Jin; Lee, Ji Hyun; Mun, Yeung-Chul

    2014-01-01

    Waldenström's macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n = 71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37–92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%, P = 0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73–111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM. PMID:24995279

  5. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina

    PubMed Central

    Lahouaoui, Hasna; Coutanson, Christine; Cooper, Howard M.; Bennis, Mohamed

    2016-01-01

    Purpose Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. Methods To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17×1014 photons/cm2/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT–PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). Results We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c-fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2

  6. Peptide receptor radionuclide therapy with 90Y-DOTATATE/90Y-DOTATOC in patients with progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity

    PubMed Central

    Vinjamuri, S; Gilbert, T M; Banks, M; McKane, G; Maltby, P; Poston, G; Weissman, H; Palmer, D H; Vora, J; Pritchard, D M; Cuthbertson, D J

    2013-01-01

    Background: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to 90Y-DOTATOC/90Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures. Methods: A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed. Results: Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare. Conclusion: In patients with progressive metastatic NETs receiving 90Y-DOTATOC/90Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit. PMID:23492685

  7. Flt3 Ligand Is Essential for Survival and Protective Immune Responses during Toxoplasmosis.

    PubMed

    Dupont, Christopher D; Harms Pritchard, Gretchen; Hidano, Shinya; Christian, David A; Wagage, Sagie; Muallem, Gaia; Tait Wojno, Elia D; Hunter, Christopher A

    2015-11-01

    Dendritic cells (DCs) are critical for resistance to Toxoplasma gondii, and infection with this pathogen leads to increased numbers of DCs at local sites of parasite replication and in secondary lymphoid organs, but the factors that regulate this expansion are poorly understood. The cytokine Flt3 ligand (Flt3L) is critical for the generation and maintenance of DCs, and Flt3L(-/-) mice were found to be highly susceptible to acute toxoplasmosis. This phenotype correlated with decreased production of IL-12 and IFN-γ, as well as impaired NK cell responses. Surprisingly, despite low basal numbers of DCs, Flt3L(-/-) mice infected with T. gondii displayed an expansion of CD8α(+) and CD11b(lo)CD8α(-) DCs. Infection also induced an expansion of parasite-specific CD4(+) and CD8(+) T cells in Flt3L(-/-) mice; however, these cells were reduced in number and displayed impaired ability to produce IFN-γ relative to wild-type controls. Exogenous IL-12 treatment partially restored NK and T cell responses in Flt3L(-/-) mice, as well as acute resistance; however, these mice eventually succumbed to toxoplasmic encephalitis, despite the presence of large numbers of DCs and T cells in the brain. These results highlight the importance of Flt3L for resistance to toxoplasmosis and demonstrate the existence of Flt3L-independent pathways that can mediate infection-induced expansion of DCs and T cell priming. PMID:26385522

  8. Role of solar conditioning in DNA repair response and survival of human epidermal keratinocytes following UV irradiation

    SciTech Connect

    Liu, S.C.; Meagher, K.; Hanawalt, P.C.

    1985-08-01

    The authors have investigated the cumulative effects of sunlight exposure upon the excision-repair of UV radiation damage to DNA in epidermal keratinocytes from human donors of different ages as well as the possible effect on DNA repair of periodic conditioning of the cultured keratinocytes with sublethal UV radiation exposures. The authors have also compared the growth properties of UV-irradiated keratinocytes derived from habitually sun-exposed and nonexposed areas from the bodies of young and aged donors. DNA repair replication in keratinocytes from habitually sun-exposed facial skin and the less sun-exposed abdominal skin of middle-aged adults was found to be similar, with respect to both the UV dose response and the time course of repair after 20 J/m2, 254 nm. Growth and survival (after exposure up to 50 J/m2, 254 nm) were greater for keratinocytes from protected areas of the upper arm of young donors (under 18 years) than for cells from their own sun-exposed areas. Growth and survival were markedly reduced for all keratinocyte cultures from aged donors, especially those cultures developed from sun-exposed areas. Nevertheless, the DNA repair response to UV radiation was similar in all cases. The evident uncoupling of UV sensitivity from DNA repair capacity remains to be understood. These studies confirm that the cumulative effect of sunlight exposure indeed contributes to some skin aging processes. However, the authors have found no indication that an overall reduction in capacity for excision-repair of UV photoproducts in keratinocyte DNA accompanies senescence in human skin.

  9. Genetic polymorphisms of DNA repair pathways influence the response to chemotherapy and overall survival of gastric cancer.

    PubMed

    Zhou, Jing; Liu, Zhi-yue; Li, Cun-bao; Gao, Shang; Ding, Li-hong; Wu, Xin-lin; Wang, Zhao-yang

    2015-04-01

    We aimed to evaluate the clinical response to platinum-based chemotherapy and treatment outcome of gastric cancer patients in the present of ERCC1, ERCC2, NBN, RAD51, and XRCC3 gene polymorphisms. A number of 415 patients of gastric cancer that received platinum-based chemotherapy were enrolled in the present study. The presence of ERCC1 rs11615 and rs2298881, ERCC2 rs1799793 and rs13181, NBN rs1805794, rs709816, and RAD51 rs1801321 and XRCC3 rs1799794 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Conditional regression analysis identified that CC genotype of ERCC1 rs11615 and AA genotype of ERCC2 rs1799793 was associated with a better response to chemotherapy in gastric cancer patients, and the odds ratio (ORs)(95% confidence interval (CI)) were 2.70(1.33-5.70) and 3.12(1.52-6.84), respectively. By the Cox analysis, the CC genotype of ERCC1 rs11615, AA genotype of ERCC2 rs1799793, and CC genotype of NBN rs1805794 were significantly associated with a longer overall survival (OS) of gastric cancer. In conclusion, our results suggest that ERCC1 rs11615, ERCC2 rs1799793, and NBN rs1805794 polymorphisms in the DNA repair pathways may influence the response to chemotherapy and OS of gastric cancer. PMID:25542228

  10. A refined risk score for acute GVHD that predicts response to initial therapy, survival and transplant-related mortality

    PubMed Central

    MacMillan, Margaret L.; Robin, Marie; Harris, Andrew C.; DeFor, Todd E.; Martin, Paul J.; Alousi, Amin; Ho, Vincent T.; Bolaños-Meade, Javier; Ferrara, James L.M.; Jones, Richard; Arora, Mukta; Blazar, Bruce R.; Holtan, Shernan G.; Jacobsohn, David; Pasquini, Marcelo; Socie, Gerard; Antin, Joseph H.; Levine, John E.; Weisdorf, Daniel J.

    2015-01-01

    To develop a novel acute graft-versus-host disease (GVHD) Risk Score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response [(complete response/partial response (CR/PR)] rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD [44% (95% CI 38–50%) vs. 68% (95% CI 66–70%), p<0.001. Patients with HR-GVHD were less likely to respond at day 28 [odds ratio (OR), 0.3, 95% CI 0.2–0.4, p<0.001], and had higher risks of mortality [relative risk (RR) 2.1, 95% CI 1.7–2.6, P<0.001] and transplant-related mortality (RR 2.5, 95% CI 2.0–3.2%, p<0.001) compared to patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy. PMID:25585275

  11. Survival and behavioural responses of the predatory ladybird beetle, Eriopis connexa populations susceptible and resistant to a pyrethroid insecticide.

    PubMed

    Spíndola, A F; Silva-Torres, C S A; Rodrigues, A R S; Torres, J B

    2013-08-01

    The ladybird beetle, Eriopis connexa (Germar) (Coleoptera: Coccinellidae), is one of the commonest predators of aphids (Hemiptera: Aphididae) in the cotton agroecosystem and in many other row and fruit crops in Brazil, and has been introduced into other countries such as the USA for purposes of aphid control. In addition, the boll weevil, Anthonomus grandis Boheman (Coleoptera: Curculionidae) is the most serious cotton pest where it occurs, including Brazil. Controlling boll weevils and other pests such as cotton defoliators still tends to involve the intense application of insecticides to secure cotton production. The pyrethroid insecticide lambda-cyhalothrin (LCT) is commonly used, but this compound is not effective against aphids; hence, a desirable strategy would be to maintain E. connexa populations in cotton fields where LCT is applied. Using populations of E. connexa resistant (Res) and susceptible (Sus) to LCT, we compared behavioural responses on treated cotton plants and under confinement on partially and fully treated surfaces, and assessed the insects' survival on treated plants compared with that of the boll weevil. The E. connexa resistant population caged on treated plants with 15 and 75 g a.i. ha-1 exhibited ≫82% survival for both insecticide concentrations compared with ≪3% and ≪17% survival for susceptible E. connexa populations and boll weevils, respectively. The response of E. connexa Res and Sus populations when released, either on the soil or on the plant canopy, indicated avoidance towards treated plants, as measured by elapsed time to assess the plant. When compared with susceptible individuals, resistant ones took longer time to suffer insecticide knockdown, had a higher recovery rate after suffering knockdown, and spent more time in the plant canopy. Based on behavioural parameters evaluated in treated arenas, no ladybird beetles exhibited repellency. However, irritability was evident, with the susceptible population exhibiting

  12. Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults.

    PubMed

    Chio, Chung-Ching; Wei, Li; Chen, Tyng Guey; Lin, Chien-Min; Shieh, Ja-Ping; Yeh, Poh-Shiow; Chen, Ruei-Ming

    2016-06-01

    OBJECT Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. METHODS Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected. RESULTS Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis. CONCLUSIONS This study shows that NOR-1 can transduce survival

  13. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    SciTech Connect

    Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  14. Serotonin activates cell survival and apoptotic death responses in cultured epithelial thyroid cells.

    PubMed

    Cerulo, Giuliana; Tafuri, Simona; De Pasquale, Valeria; Rea, Silviana; Romano, Simona; Costagliola, Anna; Della Morte, Rossella; Avallone, Luigi; Pavone, Luigi Michele

    2014-10-01

    Anatomic and physiological interactions between central serotonergic system and thyroid gland are well established. However, the effects of locally available serotonin on the thyroid functions are poorly known. Here, we first demonstrate the expression of serotonin transporter SERT and 5-HT2A receptor subtype in rat thyroid epithelial cell line FRT both at mRNA and protein levels. In order to investigate the molecular mechanisms of serotonin action, FRT cells were exposed to increasing concentrations of the amine. Low concentrations of serotonin (up to 5 μM) enhanced FRT cell growth, and ERK1/2 and SMAD2/3 phosphorylation. Cell exposure to the selective 5-HT2A receptor agonist DOI recapitulated the effects of 5-HT on ERK1/2 phosphorylation. By contrast, administration of M100907, a specific 5-HT2A receptor inhibitor, prevented 5-HT induced ERK1/2 activation. On the other hand, high doses of serotonin (50 μM up to 1 mM) activated a caspase-3 mediated apoptosis of cells. Overall, our findings demonstrate that low levels of serotonin, interacting with 5-HT2A receptor, are able to activate proliferative signals in the thyroid epithelial cells, while high levels of serotonin cause pro-apoptotic responses, thus suggesting an active role of the amine in the thyroid functions and disorders. PMID:24997405

  15. Role of a VPS41 homologue in starvation response, intracellular survival and virulence of Cryptococcus neoformans.

    PubMed

    Liu, Xiaoguang; Hu, Guowu; Panepinto, John; Williamson, Peter R

    2006-09-01

    Previous studies have demonstrated an important role for the vacuole in the virulence of the fungus Cryptococcus and studies in yeast have implicated the vacuolar protein Vps41 in copper loading of proteins such as iron transporters. However, our studies found that a cryptococcal vps41Delta strain displayed wild-type growth on media containing iron and copper chelators and normal activity of the copper-containing virulence factor laccase as well as almost normal growth at 37 degrees C and wild-type production of the virulence factor capsule. Despite these attributes, the vps41Delta mutant strain showed a dramatic attenuation of virulence in mice and co-incubation of mutant cells with the macrophage cell line, J774.16, resulted in a dramatic loss in viability of the vps41Delta mutant strain at 10 h compared with wild-type and complemented strains. Closer examination revealed that the vps41Delta mutant displayed a dramatic loss in viability after nutrient starvation which was traced to a failure to undergo G2 arrest, but there was no defect in the formation of autophagic or proteolytic vesicles. Our results indicate that VPS41 plays a key role in regulating starvation response in this pathogenic organism and that defects in cell cycle arrest are associated with attenuated pathogenic fitness in mammalian hosts. PMID:16879414

  16. Nicotinamide mononucleotide adenylyltransferase promotes hypoxic survival by activating the mitochondrial unfolded protein response

    PubMed Central

    Mao, X R; Kaufman, D M; Crowder, C M

    2016-01-01

    Gain-of-function mutations in the mouse nicotinamide mononucleotide adenylyltransferase type 1 (Nmnat1) produce two remarkable phenotypes: protection against traumatic axonal degeneration and reduced hypoxic brain injury. Despite intensive efforts, the mechanism of Nmnat1 cytoprotection remains elusive. To develop a new model to define this mechanism, we heterologously expressed a mouse Nmnat1 non-nuclear-localized gain-of-function mutant gene (m-nonN-Nmnat1) in the nematode Caenorhabditis elegans and show that it provides protection from both hypoxia-induced animal death and taxol-induced axonal pathology. Additionally, we find that m-nonN-Nmnat1 significantly lengthens C. elegans lifespan. Using the hypoxia-protective phenotype in C. elegans, we performed a candidate screen for genetic suppressors of m-nonN-Nmnat1 cytoprotection. Loss of function in two genes, haf-1 and dve-1, encoding mitochondrial unfolded protein response (mitoUPR) factors were identified as suppressors. M-nonN-Nmnat1 induced a transcriptional reporter of the mitoUPR gene hsp-6 and provided protection from the mitochondrial proteostasis toxin ethidium bromide. M-nonN-Nmnat1 was also protective against axonal degeneration in C. elegans induced by the chemotherapy drug taxol. Taxol markedly reduced basal expression of a mitoUPR reporter; the expression was restored by m-nonN-Nmnat1. Taken together, these data implicate the mitoUPR as a mechanism whereby Nmnat1 protects from hypoxic and axonal injury. PMID:26913604

  17. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    SciTech Connect

    Stea, Baldassarre . E-mail: bstea@azcc.arizona.edu; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-03-15

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.

  18. Medical school survival versus social responsibility: finances as a driving force.

    PubMed

    Brandt, E N

    1989-01-01

    Medical educators are an interesting group of people. They thrive on new knowledge. They get excited and enthusiastic, and readily adopt new ways when the evidence is sufficient. Yet, at the same time, they resist with great vehemence change in the way they do their business. Ask how often the curriculum structure is examined. Indeed, the function of most curriculum committees is to ensure that that does not happen. Ask how often the criteria for medical school admission are examined, especially with respect to the knowledge requirements. Ask how often the faculty discusses, or even examines, the expectations of society as they are expressed by alumni, legislators, or members of the public. Ask how often faculties try to determine strategies for dealing with all of these external forces. Are those strategies approached with the same degree of objectivity and data-gathering skills that would be used in examining new therapeutic regimens? Medical educators are talented, creative people. They have a very large appetite for information and great ambition to be as fine academicians as possible. It is those characteristics that have served them well, as students and as responsible academicians. Indeed, the great strength of medical education, in my view, is that medical schools take some very bright people called faculty and some very bright people called students, mix them together for four years, and graduate a group of very smart people who will then spend three years or more mixed up with some very bright and creative people. That is a strength that can-not lost. Will the future allow us to continue that in an equally effective manner? PMID:2734361

  19. Autophagy induction is a Tor- and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis.

    PubMed

    Boglev, Yeliz; Badrock, Andrew P; Trotter, Andrew J; Du, Qian; Richardson, Elsbeth J; Parslow, Adam C; Markmiller, Sebastian J; Hall, Nathan E; de Jong-Curtain, Tanya A; Ng, Annie Y; Verkade, Heather; Ober, Elke A; Field, Holly A; Shin, Donghun; Shin, Chong H; Hannan, Katherine M; Hannan, Ross D; Pearson, Richard B; Kim, Seok-Hyung; Ess, Kevin C; Lieschke, Graham J; Stainier, Didier Y R; Heath, Joan K

    2013-01-01

    Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (tti(s450)), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In tti(s450), the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in tti(s450) larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in tti(s450) larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death. PMID:23408911

  20. Surviving the heat: heterogeneity of response in Saccharomyces cerevisiae provides insight into thermal damage to the membrane

    PubMed Central

    Guyot, Stéphane; Gervais, Patrick; Young, Michael; Winckler, Pascale; Dumont, Jennifer; Davey, Hazel Marie

    2015-01-01

    Environmental heat stress impacts on the physiology and viability of microbial cells with concomitant implications for microbial activity and diversity. Previously, it has been demonstrated that gradual heating of Saccharomyces cerevisiae induces a degree of thermal resistance, whereas a heat shock results in a high level of cell death. Here, we show that the impact of exogenous nutrients on acquisition of thermal resistance differs between strains. Using single-cell methods, we demonstrate the extent of heterogeneity of the heat-stress response within populations of yeast cells and the presence of subpopulations that are reversibly damaged by heat stress. Such cells represent potential for recovery of entire populations once stresses are removed. The results show that plasma membrane permeability and potential are key factors involved in cell survival, but thermal resistance is not related to homeoviscous adaptation of the plasma membrane. These results have implications for growth and regrowth of populations experiencing environmental heat stress and our understanding of impacts at the level of the single cell. Given the important role of microbes in biofuel production and bioremediation, a thorough understanding of the impact of stress responses of populations and individuals is highly desirable. PMID:25845620

  1. The effect of decitabine dose modification and myelosuppression on response and survival in patients with myelodysplastic syndromes.

    PubMed

    Jabbour, Elias; Garcia-Manero, Guillermo; Cornelison, A Megan; Cortes, Jorge E; Ravandi, Farhad; Daver, Naval; Kadia, Tapan; Teng, Angela; Kantarjian, Hagop

    2015-02-01

    Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. A retrospective pooled analysis of two decitabine clinical trials in patients with MDS conducted Cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. In 182 patients, baseline platelet dependence was a predictor for dose modification, reduction or delay, and death (modification: p=0.006, hazard ratio [HR]=2.04; reduction/delay: p=0.011, HR=2.00; death: p=0.003, HR=1.94). Patients with dose modifications had significantly higher overall response rates versus those with none (22% vs. 10%; p=0.015). Patients with no dose modifications had faster progression to acute myeloid leukemia (AML) versus patients with dose modifications (p=0.004). Without dose modifications, patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. PMID:24844364

  2. Surviving the crisis: Adaptive wisdom, coping mechanisms and local responses to avian influenza threats in Haining, China.

    PubMed

    Zhang, Letian; Pan, Tianshu

    2008-04-01

    Based on ethnographic research conducted in the summer of 2006, this paper examines local responses to the imminent threat of avian flu in Haining County of Zhejiang Province. During our field investigation, we conducted interviews with officials from local medical institutions (including the hospitals, the animal husbandry and veterinary station, and health clinics), to bureaus of public health and agro-economy. We also visited chicken farms, restaurants and farming households. We address the following factors that commonly structured the perceptions and actions of different social actors in the area of study: The changing mode of information-sharing and communication practices in the local communities; the official drive to professionalize the emergency response management system in the county; and the coping mechanisms that helped the villagers and town residents to weather the storm of avian flu. Our field research suggests that collective survival consciousness was translated into a spirit of voluntarism during the crisis. One important practical lesson we have learned from this study is that the adaptive wisdom embedded in local memories demonstrated its operational worth as a resourceful knowledge base for ordinary farmers to deal with food shortage, famine, plague and future pandemics. PMID:27268990

  3. Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress

    PubMed Central

    Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E.

    2015-01-01

    Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant’s ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant’s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

  4. Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress.

    PubMed

    Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E

    2015-01-01

    Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant's ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant's priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

  5. Infection of Burkholderia cepacia Induces Homeostatic Responses in the Host for Their Prolonged Survival: The Microarray Perspective

    PubMed Central

    Mariappan, Vanitha; Vellasamy, Kumutha Malar; Thimma, Jaikumar; Hashim, Onn Haji; Vadivelu, Jamuna

    2013-01-01

    Burkholderia cepacia is an opportunistic human pathogen associated with life-threatening pulmonary infections in immunocompromised individuals. Pathogenesis of B. cepacia infection involves adherence, colonisation, invasion, survival and persistence in the host. In addition, B. cepacia are also known to secrete factors, which are associated with virulence in the pathogenesis of the infection. In this study, the host factor that may be the cause of the infection was elucidated in human epithelial cell line, A549, that was exposed to live B. cepacia (mid-log phase) and its secretory proteins (mid-log and early-stationary phases) using the Illumina Human Ref-8 microarray platform. The non-infection A549 cells were used as a control. Expression of the host genes that are related to apoptosis, inflammation and cell cycle as well as metabolic pathways were differentially regulated during the infection. Apoptosis of the host cells and secretion of pro-inflammatory cytokines were found to be inhibited by both live B. cepacia and its secretory proteins. In contrast, the host cell cycle and metabolic processes, particularly glycolysis/glycogenesis and fatty acid metabolism were transcriptionally up-regulated during the infection. Our microarray analysis provided preliminary insights into mechanisms of B. cepacia pathogenesis. The understanding of host response to an infection would provide novel therapeutic targets both for enhancing the host’s defences and repressing detrimental responses induced by the invading pathogen. PMID:24116227

  6. Survival of Campylobacter jejuni during Stationary Phase: Evidence for the Absence of a Phenotypic Stationary-Phase Response

    PubMed Central

    Kelly, Alison F.; Park, Simon F.; Bovill, Richard; Mackey, Bernard M.

    2001-01-01

    When Campylobacter jejuni NCTC 11351 was grown microaerobically in rich medium at 39°C, entry into stationary phase was followed by a rapid decline in viable numbers to leave a residual population of 1% of the maximum number or less. Loss of viability was preceded by sublethal injury, which was seen as a loss of the ability to grow on media containing 0.1% sodium deoxycholate or 1% sodium chloride. Resistance of cells to mild heat stress (50°C) or aeration was greatest in exponential phase and declined during early stationary phase. These results show that C. jejuni does not mount the normal phenotypic stationary-phase response which results in enhanced stress resistance. This conclusion is consistent with the absence of rpoS homologues in the recently reported genome sequence of this species and their probable absence from strain NCTC 11351. During prolonged incubation of C. jejuni NCTC 11351 in stationary phase, an unusual pattern of decreasing and increasing heat resistance was observed that coincided with fluctuations in the viable count. During stationary phase of Campylobacter coli UA585, nonmotile variants and those with impaired ability to form coccoid cells were isolated at high frequency. Taken together, these observations suggest that stationary-phase cultures of campylobacters are dynamic populations and that this may be a strategy to promote survival in at least some strains. Investigation of two spontaneously arising variants (NM3 and SC4) of C. coli UA585 showed that a reduced ability to form coccoid cells did not affect survival under nongrowth conditions. PMID:11319108

  7. Light-Induced Movements of Chloroplasts and Nuclei Are Regulated in Both Cp-Actin-Filament-Dependent and -Independent Manners in Arabidopsis thaliana

    PubMed Central

    2016-01-01

    Light-induced chloroplast movement and attachment to the plasma membrane are dependent on actin filaments. In Arabidopsis thaliana, the short actin filaments on the chloroplast envelope, cp-actin filaments, are essential for chloroplast movement and positioning. Furthermore, cp-actin-filament-mediated chloroplast movement is necessary for the strong-light-induced nuclear avoidance response. The proteins CHLOROPLAST UNUSUAL POSITIONING 1 (CHUP1), KINESIN-LIKE PROTEIN FOR ACTIN-BASED CHLOROPLAST MOVEMENT 1 (KAC1) and KAC2 are required for the generation and/or maintenance of cp-actin filaments in Arabidopsis. In land plants, CHUP1 and KAC family proteins play pivotal roles in the proper movement of chloroplasts and their attachment to the plasma membrane. Here, we report similar but distinct phenotypes in chloroplast and nuclear photorelocation movements between chup1 and kac1kac2 mutants. Measurement of chloroplast photorelocation movement indicated that kac1kac2, but not chup1, exhibited a clear strong-light-induced increase in leaf transmittance changes. The chloroplast movement in kac1kac2 depended on phototropin 2, CHUP1 and two other regulators for cp-actin filaments, PLASTID MOVEMENT IMPAIRED 1 and THRUMIN 1. Furthermore, kac1kac2 retained a weak but significant nuclear avoidance response although chup1 displayed a severe defect in the nuclear avoidance response. The kac1kac2chup1 triple mutant was completely defective in both chloroplast and nuclear avoidance responses. These results indicate that CHUP1 and the KACs function somewhat independently, but interdependently mediate both chloroplast and nuclear photorelocation movements. PMID:27310016

  8. Experimental study on light induced influence model to mice using support vector machine

    NASA Astrophysics Data System (ADS)

    Ji, Lei; Zhao, Zhimin; Yu, Yinshan; Zhu, Xingyue

    2014-08-01

    Previous researchers have made studies on different influences created by light irradiation to animals, including retinal damage, changes of inner index and so on. However, the model of light induced damage to animals using physiological indicators as features in machine learning method is never founded. This study was designed to evaluate the changes in micro vascular diameter, the serum absorption spectrum and the blood flow influenced by light irradiation of different wavelengths, powers and exposure time with support vector machine (SVM). The micro images of the mice auricle were recorded and the vessel diameters were calculated by computer program. The serum absorption spectrums were analyzed. The result shows that training sample rate 20% and 50% have almost the same correct recognition rate. Better performance and accuracy was achieved by third-order polynomial kernel SVM quadratic optimization method and it worked suitably for predicting the light induced damage to organisms.

  9. Light-induced oxidation in semihard cheeses. Evaluation of methods used to determine levels of oxidation.

    PubMed

    Mortensen, Grith; Sørensen, John; Stapelfeldt, Henrik

    2002-07-17

    Light-induced oxidation in Havarti cheese (38% fat) stored in the dark and exposed to fluorescent light was evaluated by an array of chemical, physical, and spectroscopic methods. Light-induced changes were noticeable already after short exposure times (<12 h). A clear differentiation between samples stored in the dark and samples exposed to 1000 lx fluorescent light was obtained by means of the following methods: color measurements (a values), peroxide value determinations, and evaluations of volatile oxidation products by solid-phase microextraction gas chromatography (SPME-GC). The expected changes in peroxide values in relation to storage time were not evident. Measuring free radicals by electron spin resonance spectrometry could not be done to distinguish between samples, possibly due to the conversion of radicals during sample preparation. However, significant light-exposure effects on secondary oxidation products, detected by SPME-GC, were noted for 1-pentanol, 1-hexanol, nonanal, and benzaldehyde. PMID:12105971

  10. [Light-induced production and consumption of oxygen by chloroplasts: activation and inhibition].

    PubMed

    Chan Van, N i; Nikandrov, V V; Brin, G P; Krasnovskii, A A

    1977-07-01

    Light-induced production and consumption of oxygen by pea chloroplasts are activated at certain concentrations of the solvents (diethyl ester, methyl alcohol, dimethylsulfoxide) and detergent Triton X-100. At higher concentrations of the compounds studied both reactions are inhibited. The uncouplers (methylamine and carbonyl cyanide-3-chlorophenylhydrazone) activate these processes. The agents studied have a similar effect on the processes of light-induced production and consumption of oxygen, which are limited by a common link bound to the phosphorylation site in photosystem I. The effects observed suggest that the inhibition may be due to inhibition of photosystem II, whereas the activation may be largely due to an action on photosystem I. PMID:907797

  11. Absolute Configuration from Different Multifragmentation Pathways in Light-Induced Coulomb Explosion Imaging.

    PubMed

    Pitzer, Martin; Kastirke, Gregor; Kunitski, Maksim; Jahnke, Till; Bauer, Tobias; Goihl, Christoph; Trinter, Florian; Schober, Carl; Henrichs, Kevin; Becht, Jasper; Zeller, Stefan; Gassert, Helena; Waitz, Markus; Kuhlins, Andreas; Sann, Hendrik; Sturm, Felix; Wiegandt, Florian; Wallauer, Robert; Schmidt, Lothar Ph H; Johnson, Allan S; Mazenauer, Manuel; Spenger, Benjamin; Marquardt, Sabrina; Marquardt, Sebastian; Schmidt-Böcking, Horst; Stohner, Jürgen; Dörner, Reinhard; Schöffler, Markus; Berger, Robert

    2016-08-18

    The absolute configuration of individual small molecules in the gas phase can be determined directly by light-induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X-ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break-up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light-induced CEI. PMID:27298209

  12. Experimental evidence on removing copper and light-induced degradation from silicon by negative charge

    SciTech Connect

    Boulfrad, Yacine Lindroos, Jeanette; Yli-Koski, Marko; Savin, Hele; Wagner, Matthias; Wolny, Franziska

    2014-11-03

    In addition to boron and oxygen, copper is also known to cause light-induced degradation (LID) in silicon. We have demonstrated previously that LID can be prevented by depositing negative corona charge onto the wafer surfaces. Positively charged interstitial copper ions are proposed to diffuse to the negatively charged surface and consequently empty the bulk of copper. In this study, copper out-diffusion was confirmed by chemical analysis of the near surface region of negatively/positively charged silicon wafer. Furthermore, LID was permanently removed by etching the copper-rich surface layer after negative charge deposition. These results demonstrate that (i) copper can be effectively removed from the bulk by negative charge, (ii) under illumination copper forms a recombination active defect in the bulk of the wafer causing severe light induced degradation.

  13. Light-induced cross transport phenomena in a single-component gas

    SciTech Connect

    Chermyaninov, I. V.; Chernyak, V. G.

    2013-07-15

    The cross transport processes that occur in a single-component gas in a capillary and are caused by resonance laser radiation and pressure and temperature gradients are studied. An expression for entropy production is derived using a system of kinetic Boltzmann equations in a linear approximation. The kinetic coefficients that determine the transport processes are shown to satisfy the Onsager reciprocal relations at any Knudsen numbers and any character of the elastic interaction of gas particles with the capillary surface. The light-induced baro- and thermoeffects that take place in a closed heat-insulated system in the field of resonance laser radiation are considered. Analytical expressions are obtained for the Onsager coefficients in an almost free-molecular regime. The light-induced pressure and temperature gradients that appear in a closed heat-insulated capillary under typical experimental conditions are numerically estimated.

  14. Light-induced Changes of the Carotenoid Levels in Chloroplast Envelopes 1

    PubMed Central

    Siefermann-Harms, Dorothea; Joyard, Jacques; Douce, Roland

    1978-01-01

    The carotenoid content of thylakoids and envelopes isolated from dark-or light-treated spinach (Spinacia oleracea L.) chloroplasts was compared. In thylakoids, light induced a decrease of violaxanthin parallel with a stoichiometric increase of zeaxanthin due to violaxanthin deepoxidation. In envelopes, violaxanthin was also decreased and the relative decrease was similar to thylakoids, but zeaxanthin increase was small resulting in an over-all decrease of the amount of envelope carotenoids. When violaxanthin deepoxidation in thylakoids was partly inhibited by 10 nm nigericin, violaxanthin decrease in the envelope was inhibited to a similar degree. These observations together with the absence of deepoxidase activity in isolated envelopes plus added stroma proteins suggest that light-induced violaxanthin decrease in the envelope is not caused by an envelope or stroma deepoxidase but results from violaxanthin exchange between envelope and thylakoids. PMID:16660330

  15. Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Findings Based on North Central Cancer Treatment Group (NCCTG) Trials

    PubMed Central

    Foster, Nathan R.; Qi, Yingwei; Shi, Qian; Krook, James E.; Kugler, John W.; Jett, James R.; Molina, Julian R.; Schild, Steven E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2010-01-01

    Purpose We investigated the putative surrogate endpoints (PSEs) of best response (BR), complete response (CR), confirmed response (CoR), and progression-free survival (PFS) for associations with Overall Survival (OS), and as possible surrogate endpoints for OS. Methods Individual patient (pt) data from 870 untreated ES-SCLC pts participating in 6 single-arm (274 pts) and 3 randomized trials (596 pts) were pooled. Patient-level associations between PSEs and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of PSEs assessed by the association of treatment effects on OS and individual PSEs. Trial-level surrogacy measures included: R2 from weighted least squares regression model (WLS R2), Spearman's correlation coefficient, and R2 from bivariate survival model (Copula R2). Results Median OS and PFS were 9.6 (95% CI: 9.1-10.0) and 5.5 (95% CI: 5.2-5.9) months, respectively; BR, CR, and CoR rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (HR=0.42 (95% CI: 0.35-0.51); concordance index=0.63; p<0.01), with 6-month PFS being the strongest (HR=0.41 (95% CI: 0.35-0.49); concordance index=0.66; p<0.01). At the trial-level, PFS showed the highest level of surrogacy for OS (WLS R2=0.79; Copula R2=0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (WLS R2≤0.48). Conclusion PFS was strongly associated with OS at both the patient and trial-level. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase III trials. PMID:20960500

  16. Catalyst free visible light induced cycloaddition as an avenue for polymer ligation.

    PubMed

    Lederhose, Paul; Wüst, Kilian N R; Barner-Kowollik, Christopher; Blinco, James P

    2016-05-21

    The current study introduces a tetrazole species able to perform a rapid, visible light induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC). Full conversion of the tetrazole species under mild, catalyst free conditions is reported. Importantly, the visible light ligation technology is applied as a method for the modification and ligation of polymers featuring the rapid, clean and exclusive formation of the desired cycloadduct. PMID:27004740

  17. Light-induced changes in the absorption spectrum of bacteriorhodopsin under two-wavelength excitation

    NASA Astrophysics Data System (ADS)

    Koklyushkin, A. V.; Korolev, A. E.

    2004-09-01

    The results of spectrophotometric measurements of nonlinear light-induced changes in the absorption spectrum of bacteriorhodopsin D96N occurring upon simultaneous excitation at the wavelengths 633 and 441 nm in the excitation intensity range typical for recording of dynamic holograms are presented. The quantitative conditions under which the action of the radiation at one wavelength reduces the change in the optical density caused by the radiation at the other wavelength are determined.

  18. Spin Hall effects for cold atoms in a light induced gauge potential

    SciTech Connect

    Zhu, Shi-Liang; Fu, Hao; Wu, C.-J.; Zhang, S.-C.; Duan, L.-M. /Michigan U., MCTP

    2010-03-16

    We propose an experimental scheme to observe spin Hall effects with cold atoms in a light induced gauge potential. Under an appropriate configuration, the cold atoms moving in a spatially varying laser field experience an effective spin-dependent gauge potential. Through numerical simulation, we demonstrate that such a gauge field leads to observable spin Hall currents under realistic conditions. We also discuss the quantum spin Hall state in an optical lattice.

  19. The Breakdown of Stored Triacylglycerols Is Required during Light-Induced Stomatal Opening.

    PubMed

    McLachlan, Deirdre H; Lan, Jue; Geilfus, Christoph-Martin; Dodd, Antony N; Larson, Tony; Baker, Alison; Hõrak, Hanna; Kollist, Hannes; He, Zhesi; Graham, Ian; Mickelbart, Michael V; Hetherington, Alistair M

    2016-03-01

    Stomata regulate the uptake of CO2 and the loss of water vapor [1] and contribute to the control of water-use efficiency [2] in plants. Although the guard-cell-signaling pathway coupling blue light perception to ion channel activity is relatively well understood [3], we know less about the sources of ATP required to drive K(+) uptake [3-6]. Here, we show that triacylglycerols (TAGs), present in Arabidopsis guard cells as lipid droplets (LDs), are involved in light-induced stomatal opening. Illumination induces reductions in LD abundance, and this involves the PHOT1 and PHOT2 blue light receptors [3]. Light also induces decreases in specific TAG molecular species. We hypothesized that TAG-derived fatty acids are metabolized by peroxisomal β-oxidation to produce ATP required for stomatal opening. In silico analysis revealed that guard cells express all the genes required for β-oxidation, and we showed that light-induced stomatal opening is delayed in three TAG catabolism mutants (sdp1, pxa1, and cgi-58) and in stomata treated with a TAG breakdown inhibitor. We reasoned that, if ATP supply was delaying light-induced stomatal opening, then the activity of the plasma membrane H(+)-ATPase should be reduced at this time. Monitoring changes in apoplastic pH in the mutants showed that this was the case. Together, our results reveal a new role for TAGs in vegetative tissue and show that PHOT1 and PHOT2 are involved in reductions in LD abundance. Reductions in LD abundance in guard cells of the lycophyte Selaginella suggest that TAG breakdown may represent an evolutionarily conserved mechanism in light-induced stomatal opening. PMID:26898465

  20. Light-induced noncentrosymmetry in acceptor-donor-substituted azobenzene solutions

    NASA Astrophysics Data System (ADS)

    Zhao, Jiang; Si, Jinhai; Wang, Yougui; Ye, Peixian; Fu, Xingfa; Qiu, Ling; Shen, Yuquan

    1995-10-01

    Light-induced noncentrosymmetry was achieved experimentally in acceptor-donor-substituted azobenzene solutions and observed by phase-matched nondegenerate six-wave mixing. The microscopic origin of the induced noncentrosymmetry was found to be orientational hole burning, which was distinguished directly with net orientation of molecules by experimental observations. The decay time of the induced noncentrosymmetry depended on the rotational orientation time of the sample's molecule, which varied linearly with the viscosity of the solvent.

  1. Visible-Light-Induced Specific Desulfurization of Cysteinyl Peptide and Glycopeptide in Aqueous Solution.

    PubMed

    Gao, Xiao-Fei; Du, Jing-Jing; Liu, Zheng; Guo, Jun

    2016-03-01

    Visible-light-induced specific desulfurization of cysteinyl peptides has been explored. The photocatalytic desulfurization catalyzed by Ru(bpy)3(2+) can proceed efficiently at room temperature in aqueous solution or in binary mixtures of aqueous/organic solvent and be compatible with the presence of residues of amino acids, carbohydrates, and various sulfur-containing functional groups. This approach was successfully applied to synthesize linear and cyclic peptides through the ligation-desulfurization protocol. PMID:26892036

  2. Hysteresis upon light-induced hydrodynamic reorientation of the director of a nematic liquid crystal

    SciTech Connect

    Akopyan, R S; Alaverdyan, R B; Vardanyan, A S; Chilingaryan, Yu S

    2000-08-31

    Oscillations and hysteresis in the behaviour of the director of a nematic liquid crystal were observed upon its light-induced hydrodynamic reorientation caused by direct volume expansion. The light propagated through the liquid crystal placed between crossed polarisers provides the feedback. This light falls back on the liquid crystal and is absorbed by producing the volume expansion. A theory is suggested that describes the observed behaviour of the director of the nematic liquid crystal. (laser applications and other topics in quantum electronics)

  3. Spatial Symmetry Breaking in the Belousov-Zhabotinsky Reaction with Light-Induced Remote Communication

    SciTech Connect

    Hildebrand, M.; Skodt, H.; Showalter, K.

    2001-08-20

    Domains containing spiral waves form on a stationary background in a photosensitive Belousov-Zhabotinsky reaction with light-induced alternating nonlocal feedback. Complex behavior of colliding and splitting wave fragments is found with feedback radii comparable to the spiral wavelength. A linear stability analysis of the uniform stationary states in an Oregonator model reveals a spatial symmetry breaking instability. Numerical simulations show behavior in agreement with that found experimentally and also predict a variety of other new patterns.

  4. Ambient temperature catalyst-free light-induced preparation of macrocyclic aliphatic polyesters.

    PubMed

    Josse, Thomas; Altintas, Ozcan; Oehlenschlaeger, Kim K; Dubois, Philippe; Gerbaux, Pascal; Coulembier, Olivier; Barner-Kowollik, Christopher

    2014-02-25

    The light induced, catalyst-free ambient temperature preparation of macrocyclic aliphatic polyesters is pioneered. Based on the photo-induced Diels-Alder reaction of orthoquinodimethane and acrylate moieties, cyclic polyesters of high purity are readily synthesized. Considering the high tolerance to functional groups and the orthogonality of the ligation, the reported protocol can be easily transferred to a large range of polymers, complex topologies (tadpole, sun-shaped, jellyfish, etc.) and applications. PMID:24413149

  5. The Breakdown of Stored Triacylglycerols Is Required during Light-Induced Stomatal Opening

    PubMed Central

    McLachlan, Deirdre H.; Lan, Jue; Geilfus, Christoph-Martin; Dodd, Antony N.; Larson, Tony; Baker, Alison; Hõrak, Hanna; Kollist, Hannes; He, Zhesi; Graham, Ian; Mickelbart, Michael V.; Hetherington, Alistair M.

    2016-01-01

    Summary Stomata regulate the uptake of CO2 and the loss of water vapor [1] and contribute to the control of water-use efficiency [2] in plants. Although the guard-cell-signaling pathway coupling blue light perception to ion channel activity is relatively well understood [3], we know less about the sources of ATP required to drive K+ uptake [3, 4, 5, 6]. Here, we show that triacylglycerols (TAGs), present in Arabidopsis guard cells as lipid droplets (LDs), are involved in light-induced stomatal opening. Illumination induces reductions in LD abundance, and this involves the PHOT1 and PHOT2 blue light receptors [3]. Light also induces decreases in specific TAG molecular species. We hypothesized that TAG-derived fatty acids are metabolized by peroxisomal β-oxidation to produce ATP required for stomatal opening. In silico analysis revealed that guard cells express all the genes required for β-oxidation, and we showed that light-induced stomatal opening is delayed in three TAG catabolism mutants (sdp1, pxa1, and cgi-58) and in stomata treated with a TAG breakdown inhibitor. We reasoned that, if ATP supply was delaying light-induced stomatal opening, then the activity of the plasma membrane H+-ATPase should be reduced at this time. Monitoring changes in apoplastic pH in the mutants showed that this was the case. Together, our results reveal a new role for TAGs in vegetative tissue and show that PHOT1 and PHOT2 are involved in reductions in LD abundance. Reductions in LD abundance in guard cells of the lycophyte Selaginella suggest that TAG breakdown may represent an evolutionarily conserved mechanism in light-induced stomatal opening. PMID:26898465

  6. Light-induced processes on atoms and clusters confined in nanoporous silica and organic films

    NASA Astrophysics Data System (ADS)

    Moi, L.; Burchianti, A.; Bogi, A.; Marinelli, C.; Maibohm, C.; Mariotti, E.

    2007-03-01

    The study of light induced processes on atoms and nanoparticles confined in organic films or in dielectric structures is motivated both by fundamental interest and applications in optics and photonics. Depending on the light intensity and frequency and the kind of confinement, different processes can be activated. Among them photodesorption processes have a key role. Non thermal light induced atomic desorption has been observed from siloxane and paraffin films previously exposed to alkali vapors. This effect has been extensively investigated and used both to develop photo-atom sources and to load magneto-optical traps. Recently we observed huge photodesorption of alkali atoms embedded in nanoporous silica. In this case the atomic photodesorption causes, by properly tuning the light frequency, either formation or evaporation of clusters inside the silica matrix. Green-blue light desorbs isolated adatoms from the glass surface eventually producing clusters, whereas red-near infrared (NIR) light causes cluster evaporation due to direct excitation of surface plasmon oscillations. Green-blue light induces cluster formation taking advantage of the dense atomic vapor, which diffuses through the glass nano-cavities. Both processes are reversible and even visible to the naked eye. By alternatively illuminating the porous glass sample with blue-green and red-NIR light we demonstrate that the glass remembers the illumination sequences behaving as an effective rereadable and rewritable optical medium.

  7. Light-induced Voc increase and decrease in high-efficiency amorphous silicon solar cells

    NASA Astrophysics Data System (ADS)

    Stuckelberger, M.; Riesen, Y.; Despeisse, M.; Schüttauf, J.-W.; Haug, F.-J.; Ballif, C.

    2014-09-01

    High-efficiency amorphous silicon (a-Si:H) solar cells were deposited with different thicknesses of the p-type amorphous silicon carbide layer on substrates of varying roughness. We observed a light-induced open-circuit voltage (Voc) increase upon light soaking for thin p-layers, but a decrease for thick p-layers. Further, the Voc increase is enhanced with increasing substrate roughness. After correction of the p-layer thickness for the increased surface area of rough substrates, we can exclude varying the effective p-layer thickness as the cause of the substrate roughness dependence. Instead, we explain the observations by an increase of the dangling-bond density in both the p-layer—causing a Voc increase—and in the intrinsic absorber layer, causing a Voc decrease. We present a mechanism for the light-induced increase and decrease, justified by the investigation of light-induced changes of the p-layer and supported by Advanced Semiconductor Analysis simulation. We conclude that a shift of the electron quasi-Fermi level towards the conduction band is the reason for the observed Voc enhancements, and poor amorphous silicon quality on rough substrates enhances this effect.

  8. Amelioration of light-induced retinal degeneration by a calcium overload blocker. Flunarizine.

    PubMed

    Edward, D P; Lam, T T; Shahinfar, S; Li, J; Tso, M O

    1991-04-01

    Although free radical formation and lipid peroxidation have been implicated in photoreceptor degeneration following continuous light exposure, recent evidence led us to hypothesize that excessive stimulation of the photoreceptor cells in prolonged light exposure may cause intracellular calcium overload and consequent photoreceptor cell injury. To test this hypothesis, we studied the effects of flunarizine hydrochloride, a calcium overload blocker that inhibits the inositol 1,4,5-triphosphate-induced release of intracellular stores of calcium, in an established rat model of light-induced retinal degeneration. Light and electron microscopic examination of the flunarizine-treated retinas revealed remarkable preservation of the retinal pigment epithelium, rod inner and outer segments, nuclei, and synapses of the photoreceptor cells at all phases of the recovery period. This observation was further supported by morphometric evaluation of the outer nuclear layer thickness, which revealed a greater preservation of the photoreceptor nuclei in the drug-treated animals at 6 and 14 days after exposure. In addition, the rhodopsin levels in the flunarizine-treated retinas were also significantly higher than in the controls in all phases of recovery. The ability of flunarizine to ameliorate light-induced retinal degeneration in the rat supports our hypothesis that elevated intracellular calcium may indeed play a role in light-induced photoreceptor degeneration. PMID:2012559

  9. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

    PubMed Central

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C.; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Background: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. Patients and Methods: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6–6.5) and the median OS was 17.1 months (8.8–25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12–0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06–0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. Conclusion: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS. PMID:27242530

  10. βIII-Tubulin alters glucose metabolism and stress response signaling to promote cell survival and proliferation in glucose-starved non-small cell lung cancer cells.

    PubMed

    Parker, Amelia L; Turner, Nigel; McCarroll, Joshua A; Kavallaris, Maria

    2016-08-01

    Non-small cell lung cancer (NSCLC) survival rates are dismal and high βIII-tubulin expression is associated with chemotherapy drug resistance and tumor aggressiveness in this disease. Mounting evidence supports a role for βIII-tubulin in promoting cell survival in the harsh tumor microenvironment, which is characterized by poor nutrient supply. This study aimed to investigate the role of βIII-tubulin in glucose stress response signaling and the survival and proliferation of NSCLC cells. This study revealed that βIII-tubulin regulates cellular metabolism and glucose stress response signaling in NSCLC cells to promote cell survival and proliferation in glucose starvation. βIII-Tubulin decreases the reliance of cells on glycolytic metabolism, priming them to cope with variable nutrient supply present within the tumor microenvironment. βIII-Tubulin protects cells from endoplasmic reticulum (ER) stress and reduces both basal and glucose starvation-induced autophagy to maintain cell survival and proliferation. βIII-Tubulin enables rapid Akt activation in response to glucose starvation and co-immunoprecipitates with the master regulator of the ER stress response GRP78. Furthermore, suppression of βIII-tubulin delays the association of GRP78 with Akt in response to glucose starvation with the potential to influence Akt activation and ER homeostasis under these conditions. Together these results identify that βIII-tubulin regulates glucose metabolism and alters glucose starvation stress signaling to promote cell proliferation and survival in NSCLC cells. This elucidates a hitherto unknown role for this microtubule protein and provides insight into correlations between high βIII-tubulin expression and poor patient outcome in this disease. PMID:27207668

  11. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

    SciTech Connect

    Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung; Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae; Moon, Sung Ho; Shin, Kyung Hwan; Kim, Sang Soo; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-11-15

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, and CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.

  12. Study on the visible-light-induced photokilling effect of nitrogen-doped TiO2 nanoparticles on cancer cells.

    PubMed

    Li, Zheng; Mi, Lan; Wang, Pei-Nan; Chen, Ji-Yao

    2011-01-01

    Nitrogen-doped TiO2 (N-TiO2) nanoparticles were prepared by calcining the anatase TiO2 nanoparticles under ammonia atmosphere. The N-TiO2 showed higher absorbance in the visible region than the pure TiO2. The cytotoxicity and visible-light-induced phototoxicity of the pure- and N-TiO2 were examined for three types of cancer cell lines. No significant cytotoxicity was detected. However, the visible-light-induced photokilling effects on cells were observed. The survival fraction of the cells decreased with the increased incubation concentration of the nanoparticles. The cancer cells incubated with N-TiO2 were killed more effectively than that with the pure TiO2. The reactive oxygen species was found to play an important role on the photokilling effect for cells. Furthermore, the intracellular distributions of N-TiO2 nanoparticles were examined by laser scanning confocal microscopy. The co-localization of N-TiO2 nanoparticles with nuclei or Golgi complexes was observed. The aberrant nuclear morphologies such as micronuclei were detected after the N-TiO2-treated cells were irradiated by the visible light. PMID:21711880

  13. Photocarrier Radiometry Investigation of Light-Induced Degradation of Boron-Doped Czochralski-Grown Silicon Without Surface Passivation

    NASA Astrophysics Data System (ADS)

    Wang, Qian; Li, Bincheng

    2016-04-01

    Light-induced degradation (LID) effects of boron-doped Cz silicon wafers without surface passivation are investigated in details by photocarrier radiometry (PCR). The resistivity of all samples is in the range of 0.006 Ω {\\cdot } {cm} to 38 Ω {\\cdot } {cm}. It is found that light-induced changes in surface state occupation have a great effect on LID under illumination. With the increasing contribution of light-induced changes in surface state occupation, the generation rate of the defect decreases. The light-induced changes in surface state occupation and light-induced degradation dominate the temporal behaviors of the excess carrier density of high- and low-resistivity Si wafers, respectively. Moreover, the temporal behaviors of PCR signals of these samples under laser illumination with different powers, energy of photons, and multiple illuminations were also analyzed to understand the light-induced change of material properties. Based on the nonlinear dependence of PCR signal on the excitation power, a theoretical model taking into account both light-induced changes in surface state occupation and LID processes was proposed to explain those temporal behaviors.

  14. Phase-matched light-induced scattering, mirrorless self-oscillation, and generation of nearly retropropagating waves in LiNbO3:Fe in ``forbidden'' interaction geometry

    NASA Astrophysics Data System (ADS)

    Ilyenkov, A. V.; Odoulov, S. G.; Soskin, M. S.; Vasnetsov, M. V.

    1992-12-01

    Two mutually incoherent pump waves impinging symmetrically on a LiNbO3:Fe crystal from different faces in a plane normal to the C-axis produce chartacteristic patterns of light-induced scattering (lines and rings) and a pair of collimated waves propagating roughly in backward directions with respect to the pump waves. We show that the bright line of scattered light is in fact the mirrorless oscillation due to backward-wave four-wave mixing in the crystal with local (photovoltaic) response, while the retropropagating waves appear only because of high-order diffraction processes.

  15. Galectin 3 acts as an enhancer of survival responses in H. pylori-infected gastric cancer cells.

    PubMed

    Subhash, Vinod Vijay; Ho, Bow

    2016-02-01

    Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response to Helicobacter pylori infection. However, the significance of Gal-3 expression in H. pylori-infected cells is not well established. We analyzed Gal-3 intracellular expression, localization, and its effects in H. pylori-infected gastric epithelial cells. The predominantly nuclear confined Gal-3 was shown to be upregulated and exported out to the cytoplasm in H. pylori-infected AGS cells. The nuclear export was channeled through CRM-1 (exportin-1) protein. Interestingly, knock down of Gal-3 expression led to reduced NF-κB promoter activity and interleukin-8 (IL-8) secretion, suggesting its pro-inflammatory roles. Furthermore, Gal-3 was found to be pro-proliferative and anti-apoptotic in nature, as its knock down caused a reduction in cell proliferation and an increase in apoptosis, respectively. Taken together, our data suggest the expression and upregulation of Gal-3 as a critical endogenous event in H. pylori infection that interferes with various intracellular events, causing prolonged cell survival, which is characteristic in carcinogenesis. PMID:27044250

  16. SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy

    PubMed Central

    Storaci, Alessandra Maria; Annovazzi, Laura; Cassoni, Paola; Melcarne, Antonio; De Blasio, Pasquale; Schiffer, Davide; Biunno, Ida

    2015-01-01

    The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells. In 412 formalin-fixed and paraffin-embedded brain tumors and 39 Glioblastoma multiforme (GBM) cell lines, we determined the frequency of five SEL1L single nucleotide genetic variants with regulatory and coding functions by a SNaPShot™ assay. We tested their possible association with brain tumor risk, prognosis and therapy. We studied the in vitro cytotoxicity of valproic acid (VPA), temozolomide (TMZ), doxorubicin (DOX) and paclitaxel (PTX), alone or in combination, on 11 GBM cell lines, with respect to the SNP rs12435998 genotype. The SNP rs12435998 was prevalent in anaplastic and malignant gliomas, and in meningiomas of all histologic grades, but unrelated to brain tumor risks. In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy. GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA. PMID:25948789

  17. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    PubMed

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells. PMID:25144495

  18. Dietary Korean mistletoe enhances cellular non-specific immune responses and survival of Japanese eel (Anguilla japonica).

    PubMed

    Choi, Sang-Hoon; Park, Kwan-Ha; Yoon, Taek-Joon; Kim, Jong-Bae; Jang, Yong-Suk; Choe, Chung Hyeon

    2008-01-01

    The present study was performed to investigate the immunostimulatory effects of Korean mistletoe extract (KM-110; Viscum album Coloratum) on the non-specific immune response and protection against Aeromonas hydrophila infection in Japanese eel (Anguilla japonica). Eels were fed under 4 regimes, 0%, 0.1%, 0.5% and 1.0% KM-110 mixed diet. On day 14 after feeding, 15 fish from each group were injected i.p. with live A. hydrophila (3 x 10(6)CFU) and the remaining unchallenged fish from each group were used to study the innate immune response. On 14 days post-infection, the total survival rates were 26.6% in control, and 33.3%, 66.6% and 80% in 0.1%, 0.5% and 1% KM-110-treated groups, respectively. The maximum lysozyme activity was observed in the 1% KM-110-treated group. There was no significant difference of lysozyme activity between 0.1% and 0.5% KM-110 group. Superoxide anion (O(2)(-)) production was significantly (p<0.05) augmented in the 0.5% and 1% KM-110 groups compared to the control and 0.1% KM-110 group. No significant difference of (O(2)(-) production was found between 0.5% and 1% KM-110 group. Likewise, there was a significant increase in phagocytic activity in the 0.5% KM-110 group compared with the 0.1% group (p<0.05), but no significant difference between the 0.5% and the 1% KM-110 group indicating that 0.5% KM-110 concentration is suitable for stimulating maximum phagocytic activity resulting in a high amount of ROI production. Considering the present results, KM-110 could be utilized as a promising immunostimulating substance for a diet in aquaculture. PMID:18023593

  19. Host-derived extracellular nucleic acids enhance innate immune responses, induce coagulation, and prolong survival upon infection in insects.

    PubMed

    Altincicek, Boran; Stötzel, Sabine; Wygrecka, Malgorzata; Preissner, Klaus T; Vilcinskas, Andreas

    2008-08-15

    Extracellular nucleic acids play important roles in human immunity and hemostasis by inducing IFN production, entrapping pathogens in neutrophil extracellular traps, and providing procoagulant cofactor templates for induced contact activation during mammalian blood clotting. In this study, we investigated the functions of extracellular RNA and DNA in innate immunity and hemolymph coagulation in insects using the greater wax moth Galleria mellonella a reliable model host for many insect and human pathogens. We determined that coinjection of purified Galleria-derived nucleic acids with heat-killed bacteria synergistically increases systemic expression of antimicrobial peptides and leads to the depletion of immune-competent hemocytes indicating cellular immune stimulation. These activities were abolished when nucleic acids had been degraded by nucleic acid hydrolyzing enzymes prior to injection. Furthermore, we found that nucleic acids induce insect hemolymph coagulation in a similar way as LPS. Proteomic analyses revealed specific RNA-binding proteins in the hemolymph, including apolipoproteins, as potential mediators of the immune response and hemolymph clotting. Microscopic ex vivo analyses of Galleria hemolymph clotting reactions revealed that oenocytoids (5-10% of total hemocytes) represent a source of endogenously derived extracellular nucleic acids. Finally, using the entomopathogenic bacterium Photorhabdus luminescens as an infective agent and Galleria caterpillars as hosts, we demonstrated that injection of purified nucleic acids along with P. luminescens significantly prolongs survival of infected larvae. Our results lend some credit to our hypothesis that host-derived nucleic acids have independently been co-opted in innate immunity of both mammals and insects, but exert comparable roles in entrapping pathogens and enhancing innate immune responses. PMID:18684961

  20. Quality of pathologic response and surgery correlate with survival for completely resected bladder cancer following neoadjuvant chemotherapy

    PubMed Central

    Sonpavde, Guru; Goldman, Bryan H.; Speights, V.O.; Lerner, Seth P.; Wood, David P.; Vogelzang, Nicholas J.; Trump, Donald L.; Natale, Ronald B.; Grossman, H. Barton; Crawford, E. David

    2010-01-01

    BACKGROUND In a retrospective study of SWOG-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of MVAC neoadjuvant chemotherapy [NC] before RC for bladder cancer), factors associated with improved overall survival (OS) included pathologic complete response (pCR) defined as P0, treatment with NC, completion of RC with negative margins and ≥10 pelvic lymph nodes (LNs) removed. METHODS We used stratified Cox regression to retrospectively study the association of quality of pathologic response post-RC with OS in the subset of S8710 patients that received NC and RC with negative margins. RESULTS Of 154 patients who received NC, 68 (44.2%) were

  1. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  2. Projecting demographic responses to climate change: adult and juvenile survival respond differently to direct and indirect effects of weather in a passerine population

    USGS Publications Warehouse

    Dybala, Kristen E.; Eadie, John M.; Gardali, Thomas; Seavy, Nathaniel E.; Herzog, Mark P.

    2013-01-01

    Few studies have quantitatively projected changes in demography in response to climate change, yet doing so can provide important insights into the processes that may lead to population declines and changes in species distributions. Using a long-term mark-recapture data set, we examined the influence of multiple direct and indirect effects of weather on adult and juvenile survival for a population of Song Sparrows (Melospiza melodia) in California. We found evidence for a positive, direct effect of winter temperature on adult survival, and a positive, indirect effect of prior rainy season precipitation on juvenile survival, which was consistent with an effect of precipitation on food availability during the breeding season. We used these relationships, and climate projections of significantly warmer and slightly drier winter weather by the year 2100, to project a significant increase in mean adult survival (12-17%) and a slight decrease in mean juvenile survival (4-6%) under the B1 and A2 climate change scenarios. Together with results from previous studies on seasonal fecundity and postfledging survival in this population, we integrated these results in a population model and projected increases in the population growth rate under both climate change scenarios. Our results underscore the importance of considering multiple, direct, and indirect effects of weather throughout the annual cycle, as well as differences in the responses of each life stage to climate change. Projecting demographic responses to climate change can identify not only how populations will be affected by climate change but also indicate the demographic process(es) and specific mechanisms that may be responsible. This information can, in turn, inform climate change adaptation plans, help prioritize future research, and identify where limited conservation resources will be most effectively and efficiently spent.

  3. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    PubMed Central

    Chapiro, Julius; Duran, Rafael; Lin, MingDe; Schernthaner, Rüdiger; Lesage, David; Wang, Zhijun; Savic, Lynn Jeanette; Geschwind, Jean-François

    2015-01-01

    Objectives This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). Methods This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan–Meier analysis and compared using Cox proportional hazard ratios (HR). Results Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). Conclusion The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. PMID:25636420

  4. Ultraviolet-B light induced oxidative stress: effects on antioxidant response of Spodoptera litura.

    PubMed

    Karthi, Sengodan; Sankari, R; Shivakumar, Muthugounder S

    2014-06-01

    Ultraviolet light (UV-B), which emits radiation in the range of 280-315 nm, has been used worldwide in light trapping of insect pests. In this article, we test the hypothesis that one of the duration of UV-B exposure has a differential impact on oxidative stress marker enzymes in Spodoptera litura. Effect of UV-B exposure on total protein and antioxidant activities of superoxide dismutase (SOD), catalase (CAT), peroxidases (POX) and glutathione-S-transferase (GST) were investigated in S. litura. The adults were exposed to UV-B light for various time periods (0, 30, 60, 90 and 120 min). We found that exposure to UV-B light for 30 and 60 min resulted in increased activities of POX. When the exposure time lasted for 60 and 90 min, the activities of SOD remained significantly higher than the control. However, the POX, CAT and GST activity decreased to control levels at 90 and 120 min. whereas relatively long duration exposure activates the xenobiotics detoxifying enzymes like GST and POX and CAT enzymes. Longer UV-B exposure may interfere with pesticide detoxification mechanism in insects, making them more susceptible to insecticides. PMID:24792567

  5. Suprachiasmatic Nucleus and Subparaventricular Zone Lesions Disrupt Circadian Rhythmicity but Not Light-Induced Masking Behavior in Nile Grass Rats.

    PubMed

    Gall, Andrew J; Shuboni, Dorela D; Yan, Lily; Nunez, Antonio A; Smale, Laura

    2016-04-01

    The ventral subparaventricular zone (vSPVZ) receives direct retinal input and influences the daily patterning of activity in rodents, making it a likely candidate for the mediation of acute behavioral responses to light (i.e., masking). We performed chemical lesions aimed at the vSPVZ of diurnal grass rats (Arvicanthis niloticus) using N-methyl-D,L-aspartic acid (NMA), a glutamate agonist. Following NMA lesions, we placed grass rats in various lighting conditions (e.g., 12:12 light-dark, constant dark, constant light); presented a series of light pulses at circadian times (CT) 6, 14, 18, and 22; and placed them in a 7-h ultradian cycle to assess behavioral masking. Extensive bilateral lesions of the vSPVZ disrupted the expression of circadian rhythms of activity and abolished the circadian modulation of masking responses to light, without affecting light-induced masking behavior per se. We also found that in diurnal grass rats, NMA was capable of destroying not only neurons of the vSPVZ but also those of the suprachiasmatic nucleus (SCN), even though excitotoxins have been ineffective at destroying cells within the SCN of nocturnal rodents. The vulnerability of the grass rat's SCN to NMA toxicity raises the possibility of a difference in density of receptors for glutamate between nocturnal and diurnal species. In cases in which damage extended to the SCN, masking responses to light were present and similar to those displayed by animals with damage restricted to the vSPVZ. Thus, extensive bilateral lesions of the SCN and vSPVZ disrupted the expression of circadian rhythms without affecting acute responses to light in a diurnal species. Our present and previous results suggest that retinorecipient brain areas other than the SCN or vSPVZ, such as the intergeniculate leaflet or olivary pretectal nucleus, may be responsible for the mediation of masking responses to light in the diurnal grass rat. PMID:26801650

  6. The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher’s exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS. PMID:27099096

  7. Inorganic polyphosphate regulates responses of Escherichia coli to nutritional stringencies, environmental stresses and survival in the stationary phase.

    PubMed

    Rao, N N; Kornberg, A

    1999-01-01

    The molecular mechanisms responsible for polyP accumulation in E. coli remain largely obscure. Based on the available data, a tentative model is proposed (Fig. 1; Ault-Riché et al. 1998). Inhibition by (p)ppGpp of PPX interrupts the dynamic balance between the synthesis of polyP by PPK and its hydrolysis by PPX, accounting for polyP accumulation. However, mutants lacking PhoB, the response regulator of the Pho regulon, fail to accumulate polyP even in the face of high levels of (p)ppGpp. Clearly, PhoB is required in some undefined manner. With regard to osmotic stress, the pathway to polyP accumulation is also distinct from the one identified with the activation of envZ and the associated changes in membrane functions. A tentative scheme attempting to describe the metabolic turnover of polyP is given in Fig. 4. [figure: see text] In adaptations to stress, cells must coordinate major changes in the rates of transcription, translation, and replication as well as make choices in the genes expressed (Kolter et al. 1993). PolyP could provide activated phosphates or coordinate an adaptive response by binding metals and/or specific proteins. Accumulation of polyP in E. coli and other organisms is commonly assumed to provide a reservoir of energy convertible to ATP. This seems implausible because of the turnover of ATP which consumes only a fraction of a second (Chapman and Atkinson 1977). Thus, other functions for polyP need to be considered, among them a regulatory role. PolyP, even at very low levels, is essential in E. coli for adaptations in stationary phase and for survival (Rao and Kornberg 1996). As a polyanionic polymer, polyP has chemical similarities to DNA and RNA in interactions with basic domains of proteins. Further investigation of the cellular location of polyP, its state of metabolic availability and identification of its binding partners are needed. In view of the ubiquity of polyP in eukaryotic cells (including dynamic turnover in the nuclei of some

  8. Light-induced retinal degeneration is prevented by zinc, a component in the age-related eye disease study formulation.

    PubMed

    Organisciak, Daniel; Wong, Paul; Rapp, Christine; Darrow, Ruth; Ziesel, Alison; Rangarajan, Rekha; Lang, John

    2012-01-01

    Mineral supplements are often included in multivitamin preparations because of their beneficial effects on metabolism. In this study, we used an animal model of light-induced retinal degeneration to test for photoreceptor cell protection by the essential trace element zinc. Rats were treated with various doses of zinc oxide and then exposed to intense visible light for as long as 8 h. Zinc treatment effectively prevented retinal light damage as determined by rhodopsin and retinal DNA recovery, histology and electrophoretic analysis of DNA damage and oxidized retinal proteins. Zinc oxide was particularly effective when given before light exposure and at doses two- to four-fold higher than recommended by the age-related eye disease study group. Treated rats exhibited higher serum and retinal pigment epithelial zinc levels and an altered retinal gene expression profile. Using an Ingenuity database, 512 genes with known functional annotations were found to be responsive to zinc supplementation, with 45% of these falling into a network related to cellular growth, proliferation, cell cycle and death. Although these data suggest an integrated and extensive regulatory response, zinc induced changes in gene expression also appear to enhance antioxidative capacity in retina and reduce oxidative damage arising from intense light exposure. PMID:22385127

  9. An analysis of light-induced admittance changes in rod outer segments

    PubMed Central

    Falk, G.; Fatt, P.

    1973-01-01

    that component II arises from a light-induced increase in conductance of the disk membranes which obstruct the longitudinal flow of current through the rod interior except at very high frequencies. 8. The disk-membrane conductance increase for rods suspended in a solution having the conductivity of Ringer solution is calculated to be 4·3 × 10-11 mho/rhodpsin molecule bleached, a value which is similar to what has been found for ionic channels operated by membrane potential change in the nerve membrane and by synaptic transmitter in the postjunctional membrane. 9. No component of response has been observed which could be reliably attributed to a surface membrane conductance decrease of the type observed in receptor cells in the retina. PMID:4540195

  10. A Hypothesis: Supplementation with Mushroom-Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection

    PubMed Central

    Chunchao, Han; Guo, Jian-you

    2011-01-01

    We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-α (TNF-α) and Interferon-gamma (IFN-γ) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092

  11. Light induced anisotropy and gyrotropy in the media on the basis of azo indicators

    NASA Astrophysics Data System (ADS)

    Shaverdova, Valentina; Petrova, Svetlana; Purtseladze, Anna; Tarasashvili, Lado; Obolashvili, Nino

    2011-02-01

    Azo indicators are well known in which when changing acidity they changes their properties. It was natural to expect also their appreciable changes of their polarization properties. The results of the carried out experimental research in recording media on the basis of azo indicators- homolog of the Methyl orange introduced into the polymeric matrix are presented in this work. According to the technology developed by us, the samples for the reception of which solvents with various degree of acidity, within values pH 1.68-12.45 have been created. Samples were irradiated by the light of argon laser (488 nm) actinic for them. Measurement of light induced anisotropy was carried out on a registering recorder and can be described by means of one parameter- the effective anisotropy. As standards the samples of dyes for the reception of which neutral solvent was used have been considered. In a number of dyes the values of effective anisotropy in alkaline and acid media exceed its values concerning corresponding standards. The higher homolog -Heptyl orange and Benzyl orange which are weak or insoluble in water, become water-soluble when using solvents both with acid and alkaline reaction. The interval of appearance of light induced anisotropy has been expanded. We have used the method of the zero-ellipsometry for the research arising in the same samples light induced gyrotropy. Values of circular dichroism and circular birefringence in investigated layers in neutral media have been calculated also at various values pH. In the work the received results are discussed and analyzed.

  12. Light-induced gradual activation of photosystem II in dark-grown Norway spruce seedlings.

    PubMed

    Pavlovič, Andrej; Stolárik, Tibor; Nosek, Lukáš; Kouřil, Roman; Ilík, Petr

    2016-06-01

    Gymnosperms, unlike angiosperms, are able to synthesize chlorophyll and form photosystems in complete darkness. Photosystem I (PSI) formed under such conditions is fully active, but photosystem II (PSII) is present in its latent form with inactive oxygen evolving complex (OEC). In this work we have studied light-induced gradual changes in PSII function in dark-grown cotyledons of Norway spruce (Picea abies) via the measurement of chlorophyll a fluorescence rise, absorption changes at 830 nm, thermoluminescence glow curves (TL) and protein analysis. The results indicate that in dark-grown cotyledons, alternative reductants were able to act as electron donors to PSII with inactive OEC. Illumination of cotyledons for 5 min led to partial activation of PSII, which was accompanied by detectable oxygen evolution, but still a substantial number of PSII centers remained in the so called PSII-Q(B)-non-reducing form. Interestingly, even 24 h long illumination was not sufficient for the full activation of PSII centers. This was evidenced by a weak attachment of PsbP protein and the absence of PsbQ protein in PSII particles, the absence of PSII supercomplexes, the suboptimal maximum yield of PSII photochemistry, the presence of C band in TL curve and also the presence of up-shifted Q band in TL in DCMU-treated cotyledons. This slow light-induced activation of PSII in dark-grown cotyledons could contribute to the prevention of PSII overexcitation before the light-induced increase in PSI/PSII ratio allows effective operation of linear electron flow. PMID:26901522

  13. Light-induced membrane potential and pH gradient in Halobacterium halobium envelope vesicles.

    PubMed

    Renthal, R; Lanyi, J K

    1976-05-18

    Illumination of envelope vesicles prepared from Halobacterium halobium cells causes translocation of protons from inside to outside, due to the light-induced cycling of bacteriorhodopsin. This process results in a pH gradient across the membranes, an electrical potential, and the movements of K+ and Na+. The electrical potential was estimated by following the fluorescence of a cyanine dye, 3,3'-dipentyloxadicarbocyanine. Illumination of H. halobium vesicles resulted in a rapid, reversible decrease of the dye fluorescence, by as much as 35%. This effect was not seen in nonvesicular patches of purple membrane. Observation of maximal fluorescence decreases upon ilumination of vesicles required an optimal dye/membrane protein ratio. The pH optimum for the lightinduced fluorescence decrease was 6.0. The decrease was linear with actinic light intensity up to about 4 X 10(5) ergs cn-2 s-1. Valinomycin, gramicidin, and triphenylmethylphosphonium ion all abolished the fluorescence changes. However, the light-induced pH change was enhanced by these agents. Conversely, buffered vesicles showed no pH change but gave the same or larger fluorescence changes. Thus, we have identified the fluorescence decrease with a light-induced membrane potential, inside negative. By using valinomycin-K+-induced membrane potentials, we calibrated the fluorescence decrease with calculated Nernst diffusion potentials. We found a linear dependence between potential and fluorescence decrease of 3 mV/%, up to 90 mV. When the envelope vesicles were illuminated, the total proton-motive force generated was dependent on the presence of Na+ and K+ and their concentration gradients across the membrane. In general, K+ appeared to be more permeable than Na+ and, thus, permitted development of greater pH gradients and lower electrical potentials. By calculating the total proton-motive force from the sum of the pH and potential terms, we found that the vesicles can produce proton-motive forces near--200 m

  14. Beneficial protective effect of pramipexole on light-induced retinal damage in mice.

    PubMed

    Shibagaki, Keiichi; Okamoto, Kazuyoshi; Katsuta, Osamu; Nakamura, Masatsugu

    2015-10-01

    We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h). Electrophysiological and morphologic studies were performed to evaluate the effects of the pramipexole on light-induced retinal damage in mice. Pramipexole significantly prevented the reduction of the a- and b-wave electroretinogram (ERG) amplitudes caused by light exposure in a dose-dependent manner. In parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors, loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light exposure were notably ameliorated by pramipexole. Additionally, pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro in a concentration-dependent manner. The effect of pramipexole was significant at concentrations of 10(-6) M or higher. Pramipexole also significantly prevented H2O2-induced activation of caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS) in a concentration-dependent manner ranging from 10(-5) to 10(-3) M. Furthermore, pramipexole increased the scavenging activity toward a hydroxyl radical generated from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects against light-induced retinal damage as an antioxidant and that it may be a novel and effective therapy for retinal degenerative disorders, such as dry age-related macular degeneration. PMID:26213307

  15. Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

    PubMed Central

    Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

    The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

  16. SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer

    PubMed Central

    Liao, Xin; Yu, Qianqian; Feng, Jueping; Ma, Hong; Dai, Jing; Li, Min; Chen, Jigui; Zang, Aihua; Wang, Qian; Ge, Shuwang; Qin, Kai; Cai, Juan; Yuan, Xianglin

    2013-01-01

    Background Rapid response to chemotherapy in metastatic colorectal cancer (mCRC) patients (response within 12 weeks of chemotherapy) may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs) in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens. Materials and Methods Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658). The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing Results Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively). The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002). Their significances were all maintained even after multiple testing (all pc < 0.05). The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS) (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037). None of the SNPs predicted overall survival. Conclusions Polymorphisms of solute carriers’ may be useful to predict rapid response to

  17. A synthetic erectile optogenetic stimulator enabling blue-light-inducible penile erection.

    PubMed

    Kim, Taeuk; Folcher, Marc; Doaud-El Baba, Marie; Fussenegger, Martin

    2015-05-11

    Precise spatiotemporal control of physiological processes by optogenetic devices inspired by synthetic biology may provide novel treatment opportunities for gene- and cell-based therapies. An erectile optogenetic stimulator (EROS), a synthetic designer guanylate cyclase producing a blue-light-inducible surge of the second messenger cyclic guanosine monophosphate (cGMP) in mammalian cells, enabled blue-light-dependent penile erection associated with occasional ejaculation after illumination of EROS-transfected corpus cavernosum in male rats. Photostimulated short-circuiting of complex psychological, neural, vascular, and endocrine factors to stimulate penile erection in the absence of sexual arousal may foster novel advances in the treatment of erectile dysfunction. PMID:25788334

  18. Heterogeneous nucleation and growth dynamics in the light-induced phase transition in vanadium dioxide

    DOE PAGESBeta

    Brady, Nathaniel F.; Appavoo, Kannatassen; Seo, Minah; Nag, Joyeeta; Prasankumar, Rohit P.; Haglund, Richard F.; Hilton, David J.

    2016-03-02

    Here we report on ultrafast optical investigations of the light-induced insulator-to-metal phase transition in vanadium dioxide with controlled disorder generated by substrate mismatch. These results reveal common dynamics of this optically-induced phase transition that are independent of this disorder. Lastly, above the fluence threshold for completing the transition to the rutile crystalline phase, we find a common time scale, independent of sample morphology, of 40.5 ± 2 ps that is consistent with nucleation and growth dynamics of the R phase from the parent M1 ground state.

  19. Effects of Combined Ketamine/Xylazine Anesthesia on Light Induced Retinal Degeneration in Rats

    PubMed Central

    Bolz, Sylvia; Eslava-Schmalbach, Javier; Willmann, Gabriel; Zhour, Ahmad; Zrenner, Eberhart; Fischer, M. Dominik; Gekeler, Florian

    2012-01-01

    Objectives To explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats. Methods Rats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls. Results Ketamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals. Conclusions Our results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage

  20. Dynamic creation of a light-induced terahertz guided-wave resonator.

    PubMed

    Gingras, Lauren; Blanchard, François; Georgin, Marcel; Cooke, David G

    2016-02-01

    We demonstrate a dynamic light-induced resonator for terahertz (THz) frequency light created on ultrashort time scales inside a planar waveguide. The resonator is created by patterned femtosecond photoexcitation of a one-dimensional array of photoconductive regions inside a silicon-filled parallel plate waveguide. The metal-dielectric photonic crystal is created on a 2 ps time scale, ten times faster than the 20 ps transit time of the THz light through the array. The resonance reveals itself through narrowband THz transmission enhancement with accompanying phase modulation producing an induced group delay of up to 10.8 ps near resonance. PMID:26906824

  1. Heterogeneous nucleation and growth dynamics in the light-induced phase transition in vanadium dioxide.

    PubMed

    Brady, Nathaniel F; Appavoo, Kannatassen; Seo, Minah; Nag, Joyeeta; Prasankumar, Rohit P; Haglund, Richard F; Hilton, David J

    2016-03-31

    We report on ultrafast optical investigations of the light-induced insulator-to-metal phase transition in vanadium dioxide with controlled disorder generated by substrate mismatch. These results reveal common dynamics of this optically-induced phase transition that are independent of this disorder. Above the fluence threshold for completing the transition to the rutile crystalline phase, we find a common time scale, independent of sample morphology, of [Formula: see text] ps that is consistent with nucleation and growth dynamics of the R phase from the parent M1 ground state. PMID:26932975

  2. Cold-Atom Physics Using Ultrathin Optical Fibers: Light-Induced Dipole Forces and Surface Interactions

    SciTech Connect

    Sague, G.; Vetsch, E.; Alt, W.; Meschede, D.; Rauschenbeutel, A.

    2007-10-19

    The strong evanescent field around ultrathin unclad optical fibers bears a high potential for detecting, trapping, and manipulating cold atoms. Introducing such a fiber into a cold-atom cloud, we investigate the interaction of a small number of cold cesium atoms with the guided fiber mode and with the fiber surface. Using high resolution spectroscopy, we observe and analyze light-induced dipole forces, van der Waals interaction, and a significant enhancement of the spontaneous emission rate of the atoms. The latter can be assigned to the modification of the vacuum modes by the fiber.

  3. UV light induced photodegradation of organic dye by ZnO nanocatalysts

    SciTech Connect

    Sumesh, C. K.; Patel, Bhavin; Parekh, Kinnari

    2013-06-03

    Ultraviolet light induced photocatalytic activity of ZnO nanocatalyst prepared using a wet chemical precipitation route and mineralization of the methyl orange (MO) dye has been carried out in a photocatalytic reactor. The degradation of the MO was monitored spectrophotometrically and showed a decolorization efficiency of 92% after nine hours of irradiation in the MO-ZnO/UV light system. The blue shifting of maximum peak position of the MO and the formation of extra peak at 247 nm during irradiation time advances revealed that MO degrades in the form of intermediates during the photocatalytic process.

  4. Robust Measurement of Thin-Film Photovoltaic Modules Exhibiting Light-Induced Transients: Preprint

    SciTech Connect

    Deceglie, Michael, G.; Silverman, Timothy J.; Marion, Bill; Kurtz, Sarah R.

    2015-09-09

    Light-induced changes to the current-voltage characteristic of thin-film photovoltaic modules (i.e. light-soaking effects) frustrate the repeatable measurement of their operating power. We describe best practices for mitigating, or stabilizing, light-soaking effects for both CdTe and CIGS modules to enable robust, repeatable, and relevant power measurements. We motivate the practices by detailing how modules react to changes in different stabilization methods. We also describe and demonstrate a method for validating alternative stabilization procedures, such as those relying on forward bias in the dark. Reliable measurements of module power are critical for qualification testing, reliability testing, and power rating.

  5. Formation kinetics of copper-related light-induced degradation in crystalline silicon

    SciTech Connect

    Lindroos, J. Savin, H.

    2014-12-21

    Light-induced degradation (LID) is a deleterious effect in crystalline silicon, which is considered to originate from recombination-active boron-oxygen complexes and/or copper-related defects. Although LID in both cases appears as a fast initial decay followed by a second slower degradation, we show that the time constant of copper-related degradation increases with increasing boron concentration in contrast to boron-oxygen LID. Temperature-dependent analysis reveals that the defect formation is limited by copper diffusion. Finally, interface defect density measurements confirm that copper-related LID is dominated by recombination in the wafer bulk.

  6. Heterogeneous nucleation and growth dynamics in the light-induced phase transition in vanadium dioxide

    NASA Astrophysics Data System (ADS)

    Brady, Nathaniel F.; Appavoo, Kannatassen; Seo, Minah; Nag, Joyeeta; Prasankumar, Rohit P.; Haglund, Richard F., Jr.; Hilton, David J.

    2016-03-01

    We report on ultrafast optical investigations of the light-induced insulator-to-metal phase transition in vanadium dioxide with controlled disorder generated by substrate mismatch. These results reveal common dynamics of this optically-induced phase transition that are independent of this disorder. Above the fluence threshold for completing the transition to the rutile crystalline phase, we find a common time scale, independent of sample morphology, of 40.5+/- 2 ps that is consistent with nucleation and growth dynamics of the R phase from the parent M1 ground state.

  7. Visible-Light-Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives.

    PubMed

    Xuan, Jun; Zhang, Zhao-Guo; Xiao, Wen-Jing

    2015-12-21

    Visible-light-induced radical decarboxylative functionalization of carboxylic acids and their derivatives has recently received considerable attention as a novel and efficient method to create CC and CX bonds. Generally, this visible-light-promoted decarboxylation process can smoothly occur under mild reaction conditions with a broad range of substrates and an excellent functional-group tolerance. The radical species formed from the decarboxylation step can participate in not only single photocatalytic transformations, but also dual-catalytic cross-coupling reactions by combining photoredox catalysis with other catalytic processes. Recent advances in this research area are discussed herein. PMID:26509837

  8. Robust measurement of thin-film photovoltaic modules exhibiting light-induced transients

    NASA Astrophysics Data System (ADS)

    Deceglie, Michael G.; Silverman, Timothy J.; Marion, Bill; Kurtz, Sarah R.

    2015-09-01

    Light-induced changes to the current-voltage characteristic of thin-film photovoltaic modules (i.e. light-soaking effects) frustrate the repeatable measurement of their operating power. We describe best practices for mitigating, or stabilizing, light-soaking effects for both CdTe and CIGS modules to enable robust, repeatable, and relevant power measurements. We motivate the practices by detailing how modules react to changes in different stabilization methods. We also describe and demonstrate a method for validating alternative stabilization procedures, such as those relying on forward bias in the dark. Reliable measurements of module power are critical for qualification testing, reliability testing, and power rating.

  9. Guiding and confinement of light induced by optical vortex solitons in a cubic-quintic medium.

    PubMed

    Reyna, Albert S; de Araújo, Cid B

    2016-01-01

    The observation of confinement and guiding of light induced by an optical vortex soliton (OVS) in a cubic-quintic (defocusing-focusing) medium is reported. The waveguide effect induced by the bright region of the vortex beam, is mainly due to the defocusing nonlinearity that allows the guiding of a probe beam propagating inside of the OVS dark region. The experimental results are corroborated by numerical simulations based on the cubic-quintic nonlinear Schrödinger equation, showing excellent agreement. PMID:26696191

  10. A light-inducible CRISPR/Cas9 system for control of endogenous gene activation

    PubMed Central

    Polstein, Lauren R.; Gersbach, Charles A.

    2015-01-01

    Optogenetic systems enable precise spatial and temporal control of cell behavior. We engineered a light-activated CRISPR/Cas9 effector (LACE) system that induces transcription of endogenous genes in the presence of blue light. This was accomplished by fusing the light-inducible heterodimerizing proteins CRY2 and CIB1 to a transactivation domain and the catalytically inactive dCas9, respectively. The versatile LACE system can be easily directed to new DNA sequences for the dynamic regulation of endogenous genes. PMID:25664691

  11. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  12. Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice.

    PubMed

    Muindi, Fanuel; Colas, Damien; Ikeme, Jesse; Ruby, Norman F; Heller, H Craig

    2015-01-01

    Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour) induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period. PMID:26083020

  13. Mutation of the Light-Induced Yellow Leaf 1 Gene, Which Encodes a Geranylgeranyl Reductase, Affects Chlorophyll Biosynthesis and Light Sensitivity in Rice

    PubMed Central

    Yuan, Yuan; Zhu, Jinyan; Wang, Man; Yuan, Fuhai; Wu, Shujun; Wang, Zhiqin; Yi, Chuandeng; Xu, Tinghua; Ryom, MyongChol; Gu, Minghong; Liang, Guohua

    2013-01-01

    Chlorophylls (Chls) are crucial for capturing light energy for photosynthesis. Although several genes responsible for Chl biosynthesis were characterized in rice (Oryza sativa), the genetic properties of the hydrogenating enzyme involved in the final step of Chl synthesis remain unknown. In this study, we characterized a rice light-induced yellow leaf 1-1 (lyl1-1) mutant that is hypersensitive to high-light and defective in the Chl synthesis. Light-shading experiment suggested that the yellowing of lyl1-1 is light-induced. Map-based cloning of LYL1 revealed that it encodes a geranylgeranyl reductase. The mutation of LYL1 led to the majority of Chl molecules are conjugated with an unsaturated geranylgeraniol side chain. LYL1 is the firstly defined gene involved in the reduction step from Chl-geranylgeranylated (ChlGG) and geranylgeranyl pyrophosphate (GGPP) to Chl-phytol (ChlPhy) and phytyl pyrophosphate (PPP) in rice. LYL1 can be induced by light and suppressed by darkness which is consistent with its potential biological functions. Additionally, the lyl1-1 mutant suffered from severe photooxidative damage and displayed a drastic reduction in the levels of α-tocopherol and photosynthetic proteins. We concluded that LYL1 also plays an important role in response to high-light in rice. PMID:24058671

  14. Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

    NASA Astrophysics Data System (ADS)

    Nomoto, Takahiro; Fukushima, Shigeto; Kumagai, Michiaki; Machitani, Kaori; Arnida; Matsumoto, Yu; Oba, Makoto; Miyata, Kanjiro; Osada, Kensuke; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2014-04-01

    Nanocarriers responding to light have great potential for pinpoint therapy, and recent studies have revealed promising in vivo activity. However, light-selective gene transfer still remains challenging in the systemic application. Here we report systemic light-responsive nanocarriers for gene delivery developed through the sequential self-assembly of ABC-type triblock copolymer/DNA/dendrimeric photosensitizer, forming polyplex micelles with three-layered functional nanocompartments. The DNA-packaged core is covered by the photosensitizer-incorporated intermediate layer, which is encompassed by an outer shielding shell. This three-layered structure permits multistep photosensitizer and DNA delivery into a solid tumour by a systemic route: the shielding layer minimizes unfavourable interactions with blood components, and the photosensitizer is delivered to endo-/lysosomal membranes to facilitate light-selective cytoplasmic translocation of the micelles, accomplishing DNA delivery into the nucleus to exert gene expression. The polyplex micelles display >100-fold photoenhanced gene expression in cultured cells and exhibit light-induced in vivo gene transfer in solid tumours following systemic administration.

  15. Visible light-induced photocatalytic properties of WO{sub 3} films deposited by dc reactive magnetron sputtering

    SciTech Connect

    Imai, Masahiro; Kikuchi, Maiko; Oka, Nobuto; Shigesato, Yuzo

    2012-05-15

    The authors examined the photocatalytic activity of WO{sub 3} films (thickness 500-600 nm) deposited on a fused quartz substrate heated at 350-800 deg. C by dc reactive magnetron sputtering using a W metal target under the O{sub 2} gas pressure from 1.0 to 5.0 Pa. Films deposited at 800 deg. C under 5.0 Pa have excellent crystallinity of triclinic, P1(1) structure and a large surface area, as confirmed by x-ray diffraction, scanning electron microscopy, and atomic force microscopy. Exposure of acetaldehyde (CH{sub 3}CHO) adsorbed onto the film surface to ultraviolet, visible, or standard fluorescence light induces oxidative photocatalytic decomposition indicated by a decrease in CH{sub 3}CHO concentration and generation of CO{sub 2} gas. For all three types of irradiation, concentration ratio of decreased CH{sub 3}CHO to increased CO{sub 2} is about 1:1, suggesting the possible presence of intermediates. The sputter-deposited WO{sub 3} film can be a good candidate as a visible light-responsive photocatalyst.

  16. Modeling light-induced charge transfer dynamics across a metal-molecule-metal junction: bridging classical electrodynamics and quantum dynamics.

    PubMed

    Hu, Zixuan; Ratner, Mark A; Seideman, Tamar

    2014-12-14

    We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify our approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement. PMID:25494729

  17. Modeling light-induced charge transfer dynamics across a metal-molecule-metal junction: Bridging classical electrodynamics and quantum dynamics

    NASA Astrophysics Data System (ADS)

    Hu, Zixuan; Ratner, Mark A.; Seideman, Tamar

    2014-12-01

    We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify our approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement.

  18. Modeling light-induced charge transfer dynamics across a metal-molecule-metal junction: Bridging classical electrodynamics and quantum dynamics

    SciTech Connect

    Hu, Zixuan; Ratner, Mark A.; Seideman, Tamar

    2014-12-14

    We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify our approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement.

  19. Elementary and macroscopic light-induced currents and their Ca2+-dependence in the photoreceptors of Periplaneta americana

    PubMed Central

    Immonen, Esa-Ville; Krause, Stephan; Krause, Yani; Frolov, Roman; Vähäsöyrinki, Mikko T.; Weckström, Matti

    2014-01-01

    In a microvillar photoreceptor, absorption of an incident photon initiates a phototransduction reaction that generates a depolarizing light-induced current (LIC) in the microvillus. Although in-depth knowledge about these processes in photoreceptors of the fruitfly Drosophila is available, not much is known about their nature in other insect species. Here, we present description of some basic properties of both elementary and macroscopic LICs and their Ca2+-dependence in the photoreceptors of a dark-active species, the cockroach Periplaneta americana. Cockroach photoreceptors respond to single photon absorptions by generating quantum bumps with about 5-fold larger amplitudes than in Drosophila. At the macroscopic current level, cockroach photoreceptors responded to light with variable sensitivity and current waveform. This variability could be partially attributed to differences in whole-cell capacitance. Transient LICs, both elementary and macroscopic, showed only moderate dependence on extracellular Ca2+. However, with long light pulses, response inactivation was largely abolished and the overall size of LICs increased when extracellular Ca2+ was omitted. Finally, by determining relative ionic permeabilities from reversals of LICs, we demonstrate that when compared to Drosophila, cockroach light-gated channels are only moderately Ca2+-selective. PMID:24795648

  20. Light-Induced Infrared Difference Spectroscopy in the Investigation of Light Harvesting Complexes.

    PubMed

    Mezzetti, Alberto

    2015-01-01

    Light-induced infrared difference spectroscopy (IR-DS) has been used, especially in the last decade, to investigate early photophysics, energy transfer and photoprotection mechanisms in isolated and membrane-bound light harvesting complexes (LHCs). The technique has the definite advantage to give information on how the pigments and the other constituents of the biological system (proteins, membranes, etc.) evolve during a given photoreaction. Different static and time-resolved approaches have been used. Compared to the application of IR-DS to photosynthetic Reaction Centers (RCs), however, IR-DS applied to LHCs is still in an almost pioneering age: very often sophisticated techniques (step-scan FTIR, ultrafast IR) or data analysis strategies (global analysis, target analysis, multivariate curve resolution) are needed. In addition, band assignment is usually more complicated than in RCs. The results obtained on the studied systems (chromatophores and RC-LHC supercomplexes from purple bacteria; Peridinin-Chlorophyll-a-Proteins from dinoflagellates; isolated LHCII from plants; thylakoids; Orange Carotenoid Protein from cyanobacteria) are summarized. A description of the different IR-DS techniques used is also provided, and the most stimulating perspectives are also described. Especially if used synergically with other biophysical techniques, light-induced IR-DS represents an important tool in the investigation of photophysical/photochemical reactions in LHCs and LHC-containing systems. PMID:26151118

  1. Light-induced long-range hydrogen motion in a-Si:H at room temperature

    NASA Astrophysics Data System (ADS)

    Cheong, Hyeonsik M.; Lee, S.-H.; Nelson, B. P.; Mascarenhas, A.; Deb, S. K.

    2001-03-01

    We demonstrate that one can detect minuscule amounts of hydrogen diffusion out of a-Si:H under illumination at room temperature, by monitoring the changes in the Raman spectrum of a-WO3 as a function of illumination. The Staebler-Wronski effect, the light-induce creation of metastable defects in hydrogenated amorphous silicon (a-Si:H), has been one of the major problems that has limited the performance of solar cells based on this material. The recently suggested ¡®hydrogen collision model¡¯ can explain many aspects of the Staebler-Wronski effect, but assumes that the photogenerated mobile hydrogen atoms can move a long distance at room temperature. However, light-induced hydrogen motion in a-Si:H has not been experimentally observed at room temperature. We utilized the high sensitivity of the Raman spectrum of electrochromic a-WO3 to hydrogen insertion to probe the long-range motion of hydrogen at room temperature. We deposited a thin (200 nm) layer of a-WO3 on top of a-Si:H, and under illumination, a change in the Raman spectrum was detected. By comparing the Raman signal changes with those for control experiments where hydrogen is electrochemically inserted into a-WO_3, we can estimate semiquantitatively the amount of hydrogen that diffuses out of the a-Si:H layer.

  2. Two Light-Induced Processes in the Photoreceptor Cells of Limulus Ventral Eye

    PubMed Central

    Lisman, J. E.; Brown, J. E.

    1971-01-01

    The dark-adapted current-voltage (I-V) curve of a ventral photoreceptor cell of Limulus, measured by a voltage-clamp technique, has a high slope-resistance region more negative than resting voltage, a lower slope-resistance region between resting voltage and zero, and a negative slope-resistance region more positive than 0 v. With illumination, we find no unique voltage at which there is no light-induced current. At the termination of illumination, the I-V curve changes quickly, then recovers very slowly to a dark-adapted configuration. The voltage-clamp currents during and after illumination can be interpreted to arise from two separate processes. One process (fast) changes quickly with change in illumination, has a reversal potential at +20 mv, and has an I-V curve with positive slope resistance at all voltages. These properties are consistent with a light-induced change in membrane conductance to sodium ions. The other process (slow) changes slowly with changes in illumination, generates light-activated current at +20 mv, and has an I-V curve with a large region of negative slope resistance. The mechanism of this process cannot as yet be identified. PMID:5122373

  3. A light-induced spin crossover actuated single-chain magnet

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Zheng, Hui; Kang, Soonchul; Shiota, Yoshihito; Hayami, Shinya; Mito, Masaki; Sato, Osamu; Yoshizawa, Kazunari; Kanegawa, Shinji; Duan, Chunying

    2013-11-01

    Both spin-crossover complexes and molecular nanomagnets display bistable magnetic states, potentially behaving as elementary binary units for information storage. It is a challenge to introduce spin-crossover units into molecular nanomagnets to switch the bistable state of the nanomagnets through external stimuli-tuned spin crossover. Here we report an iron(II) spin-crossover unit and paramagnetic iron(III) ions that are incorporated into a well-isolated double-zigzag chain. The chain exhibits thermally induced reversible spin-crossover and light-induced excited spin-state trapping at the iron(II) sites. Single-chain magnet behaviour is actuated accompanying the synergy between light-induced excited spin-state trapping at the iron(II) sites and ferromagnetic interactions between the photoinduced high-spin iron(II) and low-spin iron(III) ions in the chain. The result provides a strategy to switch the bistable state of molecular nanomagnets using external stimuli such as light and heat, with the potential to erase and write information at a molecular level.

  4. Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress.

    PubMed

    Jaiswal, Manish; Haelterman, Nele A; Sandoval, Hector; Xiong, Bo; Donti, Taraka; Kalsotra, Auinash; Yamamoto, Shinya; Cooper, Thomas A; Graham, Brett H; Bellen, Hugo J

    2015-07-01

    Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration--defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise. PMID:26176594

  5. Light induced effects in a-Si:H films alloyed with sulfur

    SciTech Connect

    Yoon, J.H.; Taylor, P.C.; Yan, B.; Lee, C.H.

    1997-07-01

    Light-induced effects are studied in hydrogenated amorphous silicon-sulfur alloys (a-SiS{sub x}:H) and compared to those that exist in a-Si:H. The A-SiS{sub x}:H films were grown by decomposition of pre-mixtures of SiH{sub 4} and H{sub 2}S. The light-induced effects were monitored using electrical (dark conductivity and photoconductivity, including the constant photocurrent method [CPM]) and optical (photoluminescence) measurements and electron spin resonance. It is found that sulfur alloying results in a significant reduction in the degradation in the dark- and photo-conductivity. For an a-SiS{sub x}:H film grown with a gas mixture of H{sub 2}S/SiH{sub 4} = 0.02, there is an increase of over an order of magnitude in the dark conductivity and a small decrease in the photoconductivity after 50 hours of light soaking. The subgap deep defect density as measured by CPM increases with illumination time, following a stretched exponential to saturation. The saturated defect density is an order of magnitude higher than that observed in the annealed state.

  6. Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

    PubMed Central

    Jaiswal, Manish; Haelterman, Nele A.; Sandoval, Hector; Xiong, Bo; Donti, Taraka; Kalsotra, Auinash; Yamamoto, Shinya; Cooper, Thomas A.; Graham, Brett H.; Bellen, Hugo J.

    2015-01-01

    Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise. PMID:26176594

  7. Light-induced degradation of storage starch in turions of Spirodela polyrhiza depends on nitrate.

    PubMed

    Appenroth, Klaus-J; Ziegler, Paul

    2008-10-01

    Light induces both the germination of turions of the duckweed Spirodela polyrhiza and the degradation of the reserve starch stored in the turions. The germination photoresponse requires nitrate, and we show here that nitrate is also needed for the light-induced degradation of the turion starch. Ammonium cannot substitute for nitrate in this regard, and nitrate thus acts specifically as signal to promote starch degradation in the turions. Irradiation with continuous red light leads to starch degradation via auto-phosphorylation of starch-associated glucan, water dikinase (GWD), phosphorylation of the turion starch and enhanced binding of alpha-amylase to starch granules. The present study shows that all of these processes require the presence of nitrate, and that nitrate exerts its effect on starch degradation at a point between the absorption of light by phytochrome and the auto-phosphorylation of the GWD. Nitrate acts to coordinate carbon and nitrogen metabolism in germinating turions: starch will only be broken down when sufficient nitrogen is present to ensure appropriate utilization of the released carbohydrate. These data constitute the first report of control over the initiation of reserve starch degradation by nitrate. PMID:18643949

  8. Light-induced degradation of perfluorocarboxylic acids in the presence of titanium dioxide.

    PubMed

    Dillert, Ralf; Bahnemann, Detlef; Hidaka, Hisao

    2007-03-01

    The UV-photon-induced degradation of heptafluorobutanoic acid was investigated in acidic aqueous solutions in the presence of titanium dioxide. Heptafluorobutanoic acid could be degraded with this photocatalyst in a light-induced reaction generating carbon dioxide and fluoride anions. Carbon dioxide evolution in a significant amount occurred only in the presence of molecular oxygen and the photocatalyst. The light-induced degradation of trifluoroacetic acid, pentafluoropropanoic acid, nonafluorobutanoic acid, pentadecafluorooctanoic acid, nonafluorobutanesulfonic acid, and heptadecafluorooctanesulfonic acid in the presence of titanium dioxide was also studied. The perfluorocarboxylic acids under investigation are degraded to generate CO(2) and fluoride anions while both perfluorinated sulfonic acids are persistent under the experimental conditions employed in this study. For all compounds photonic efficiencies of the mineralization reaction were estimated to be smaller than 1x10(-5). To increase the photocatalytic activity mixed systems containing homogeneous phosphotungstic acid and heterogeneous titanium dioxide catalysts were also investigated. In the mixtures of these two photocatalysts, the formation rate of CO(2) increased with illumination time. PMID:17126882

  9. Calcium-dependent protein kinase CPK6 positively functions in induction by yeast elicitor of stomatal closure and inhibition by yeast elicitor of light-induced stomatal opening in Arabidopsis.

    PubMed

    Ye, Wenxiu; Muroyama, Daichi; Munemasa, Shintaro; Nakamura, Yoshimasa; Mori, Izumi C; Murata, Yoshiyuki

    2013-10-01

    Yeast elicitor (YEL) induces stomatal closure that is mediated by a Ca(2+)-dependent signaling pathway. A Ca(2+)-dependent protein kinase, CPK6, positively regulates activation of ion channels in abscisic acid and methyl jasmonate signaling, leading to stomatal closure in Arabidopsis (Arabidopsis thaliana). YEL also inhibits light-induced stomatal opening. However, it remains unknown whether CPK6 is involved in induction by YEL of stomatal closure or in inhibition by YEL of light-induced stomatal opening. In this study, we investigated the roles of CPK6 in induction by YEL of stomatal closure and inhibition by YEL of light-induced stomatal opening in Arabidopsis. Disruption of CPK6 gene impaired induction by YEL of stomatal closure and inhibition by YEL of light-induced stomatal opening. Activation by YEL of nonselective Ca(2+)-permeable cation channels was impaired in cpk6-2 guard cells, and transient elevations elicited by YEL in cytosolic-free Ca(2+) concentration were suppressed in cpk6-2 and cpk6-1 guard cells. YEL activated slow anion channels in wild-type guard cells but not in cpk6-2 or cpk6-1 and inhibited inward-rectifying K(+) channels in wild-type guard cells but not in cpk6-2 or cpk6-1. The cpk6-2 and cpk6-1 mutations inhibited YEL-induced hydrogen peroxide accumulation in guard cells and apoplast of rosette leaves but did not affect YEL-induced hydrogen peroxide production in the apoplast of rosette leaves. These results suggest that CPK6 positively functions in induction by YEL of stomatal closure and inhibition by YEL of light-induced stomatal opening in Arabidopsis and is a convergent point of signaling pathways for stomatal closure in response to abiotic and biotic stress. PMID:23922271

  10. The energetics of the primary proton transfer in bacteriorhodopsin revisited: it is a sequential light-induced charge separation after all.

    PubMed

    Braun-Sand, Sonja; Sharma, Pankaz K; Chu, Zhen T; Pisliakov, Andrei V; Warshel, Arieh

    2008-05-01

    The light-induced proton transport in bacteriorhodopsin has been considered as a model for other light-induced proton pumps. However, the exact nature of this process is still unclear. For example, it is not entirely clear what the driving force of the initial proton transfer is and, in particular, whether it reflects electrostatic forces or other effects. The present work simulates the primary proton transfer (PT) by a specialized combination of the EVB and the QCFF/PI methods. This combination allows us to obtain sufficient sampling and a quantitative free energy profile for the PT at different protein configurations. The calculated profiles provide new insight about energetics of the primary PT and its coupling to the protein conformational changes. Our finding confirms the tentative analysis of an earlier work (A. Warshel, Conversion of light energy to electrostatic energy in the proton pump of Halobacterium halobium, Photochem. Photobiol. 30 (1979) 285-290) and determines that the overall PT process is driven by the energetics of the charge separation between the Schiff base and its counterion Asp85. Apparently, the light-induced relaxation of the steric energy of the chromophore leads to an increase in the ion-pair distance, and this drives the PT process. Our use of the linear response approximation allows us to estimate the change in the protein conformational energy and provides the first computational description of the coupling between the protein structural changes and the PT process. It is also found that the PT is not driven by twist-modulated changes of the Schiff base's pKa, changes in the hydrogen bond directionality, or other non-electrostatic effects. Overall, based on a consistent use of structural information as the starting point for converging free energy calculations, we conclude that the primary event should be described as a light-induced formation of an unstable ground state, whose relaxation leads to charge separation and to the

  11. Responses Of Subalpine Conifer Seedling Germination And Survival To Soil Microclimate In The Alpine Treeline Warming Experiment

    NASA Astrophysics Data System (ADS)

    Castanha, C.; Moyes, A. B.; Torn, M. S.; Germino, M. J.; Kueppers, L. M.

    2011-12-01

    At Niwot Ridge, Colorado, we used common gardens and climate manipulations to investigate potential subalpine tree species range shifts due to climate change. In Fall 2009 we harvested seed from local populations of limber pine and Englemann spruce, which we sowed in 3 experimental sites spanning an elevation gradient from lower subalpine forest (3080m asl), to the upper subalpine treeline ecotone (3400m asl), to the alpine tundra (3550m asl). In October we turned on overhead infrared heaters designed to increase growing season surface soil temperature by 4-5°C, and following snowmelt in 2010 we crossed this heating treatment with manual watering, adding 3mm of water each week. Here we report on the species, site, and treatment effects on seedling emergence and survival as mediated by snowmelt date, soil temperature, and soil moisture. Depending on the site and plot, heating accelerated germination by 1 to 4 weeks. Germination degree days (heat accumulation required for seed germination) were greater for pine than for spruce and greater in drier plots. Seedling survival was explained by date of emergence, with older seedlings more likely to survive the season. Survival was also explained by drought degree days -- the number of days below critical soil moisture thresholds compounded by high temperature -- with lower thresholds for spruce than for pine. Our preliminary results indicate that a warmer environment will stimulate germination for both species, but that, survival - especially for spruce - will be critically modulated by summer soil moisture.

  12. Light-Induced Stomatal Opening Is Affected by the Guard Cell Protein Kinase APK1b

    PubMed Central

    Elhaddad, Nagat S.; Hunt, Lee; Sloan, Jennifer; Gray, Julie E.

    2014-01-01

    Guard cells allow land plants to survive under restricted or fluctuating water availability. They control the exchange of gases between the external environment and the interior of the plant by regulating the aperture of stomatal pores in response to environmental stimuli such as light intensity, and are important regulators of plant productivity. Their turgor driven movements are under the control of a signalling network that is not yet fully characterised. A reporter gene fusion confirmed that the Arabidopsis APK1b protein kinase gene is predominantly expressed in guard cells. Infrared gas analysis and stomatal aperture measurements indicated that plants lacking APK1b are impaired in their ability to open their stomata on exposure to light, but retain the ability to adjust their stomatal apertures in response to darkness, abscisic acid or lack of carbon dioxide. Stomatal opening was not specifically impaired in response to either red or blue light as both of these stimuli caused some increase in stomatal conductance. Consistent with the reduction in maximum stomatal conductance, the relative water content of plants lacking APK1b was significantly increased under both well-watered and drought conditions. We conclude that APK1b is required for full stomatal opening in the light but is not required for stomatal closure. PMID:24828466

  13. Light-induced stomatal opening is affected by the guard cell protein kinase APK1b.

    PubMed

    Elhaddad, Nagat S; Hunt, Lee; Sloan, Jennifer; Gray, Julie E

    2014-01-01

    Guard cells allow land plants to survive under restricted or fluctuating water availability. They control the exchange of gases between the external environment and the interior of the plant by regulating the aperture of stomatal pores in response to environmental stimuli such as light intensity, and are important regulators of plant productivity. Their turgor driven movements are under the control of a signalling network that is not yet fully characterised. A reporter gene fusion confirmed that the Arabidopsis APK1b protein kinase gene is predominantly expressed in guard cells. Infrared gas analysis and stomatal aperture measurements indicated that plants lacking APK1b are impaired in their ability to open their stomata on exposure to light, but retain the ability to adjust their stomatal apertures in response to darkness, abscisic acid or lack of carbon dioxide. Stomatal opening was not specifically impaired in response to either red or blue light as both of these stimuli caused some increase in stomatal conductance. Consistent with the reduction in maximum stomatal conductance, the relative water content of plants lacking APK1b was significantly increased under both well-watered and drought conditions. We conclude that APK1b is required for full stomatal opening in the light but is not required for stomatal closure. PMID:24828466

  14. Survival Outcome Assessed According to Tumor Response and Shrinkage Pattern in Patients with EGFR Mutation–Positive Non–Small-Cell Lung Cancer Treated with Gefitinib or Erlotinib

    PubMed Central

    Takeda, Masayuki; Nakagawa, Kazuhiko

    2014-01-01

    Introduction: Somatic mutations in the epidermal growth factor receptor gene (EGFR) are associated with a marked therapeutic response to EGFR–tyrosine kinase inhibitors (TKIs) in patients with advanced non–small cell lung cancer (NSCLC). Clinical indicators of the likely survival benefit of EGFR-TKI treatment in NSCLC patients with EGFR mutations have not been identified, however. We therefore evaluated progression-free survival (PFS) and overall survival (OS) according to tumor response and tumor shrinkage pattern in such patients. Methods: Among 145 EGFR mutation–positive NSCLC patients treated with EGFR-TKIs, 68 individuals were selected for analysis. Results: Of the 68 selected patients, 6 achieved a complete response (CR), 42 a partial response (PR), and 14 stable disease (SD). Both PFS and OS were significantly longer in patients who achieved a CR or PR than in those who experienced SD. Multivariate analysis showed that a response (CR or PR) to EGFR-TKIs was significantly associated with both PFS and OS. Among the CR/PR group, the median maximal tumor shrinkage relative to baseline was 56%, and the median time to response (TTR) was 4.2 weeks. The subsets of these patients who experienced rapid tumor regression (TTR of ≤4.2 weeks) or a high degree of tumor shrinkage (≥56%) did not show a more favorable PFS or OS compared with those who experienced slow tumor regression or a low degree of tumor shrinkage. Conclusion: Response (CR or PR) may represent the optimal surrogate for efficacy among EGFR mutation–positive NSCLC patients treated with EGFR-TKIs. PMID:24419417

  15. ZEB1 Links p63 and p73 in a Novel Neuronal Survival Pathway Rapidly Induced in Response to Cortical Ischemia

    PubMed Central

    Bui, Thai; Sequeira, Judith; Wen, Tong Chun; Sola, Augusto; Higashi, Yujiro; Kondoh, Hisato; Genetta, Tom

    2009-01-01

    Background Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage. Methodology/Principal Findings We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia. Employing histological, tissue culture, and molecular biological read-outs, we show that this novel pro-survival response, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. We show further that this phylogenetically conserved pathway is induced as well in the human cortex subjected to episodes of clinically relevant stroke. Conclusions/Significance The data presented here provide the first evidence that ZEB1 induction is part of a protective response by neurons to ischemia. The stroke-induced increase in ZEB1 mRNA and protein levels in cortical neurons is both developmentally and phylogenetically conserved and may therefore be part of a fundamental cellular response to this insult. Beyond the context of stroke, the finding that ZEB1 is regulated by a member of the p53 family has implications for cell survival in other tissue and cellular environments subjected to ischemia, such as the myocardium and, in particular, tumor masses. PMID:19194497

  16. A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi

    PubMed Central

    Francis, H.; Bates, M. J.; Kalilani, L.

    2012-01-01

    Background. Human-Immunodeficiency-Virus- (HIV-) related Kaposi's sarcoma (KS) has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART) were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA) Palliative Outcome Scale (POS). Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial. PMID:22496970

  17. The Staphylococcus aureus Alternative Sigma Factor ςB Controls the Environmental Stress Response but Not Starvation Survival or Pathogenicity in a Mouse Abscess Model

    PubMed Central

    Chan, Pan F.; Foster, Simon J.; Ingham, Eileen; Clements, Mark O.

    1998-01-01

    The role of ςB, an alternative sigma factor of Staphylococcus aureus, has been characterized in response to environmental stress, starvation-survival and recovery, and pathogenicity. ςB was mainly expressed during the stationary phase of growth and was repressed by 1 M sodium chloride. A sigB insertionally inactivated mutant was created. In stress resistance studies, ςB was shown to be involved in recovery from heat shock at 54°C and in acid and hydrogen peroxide resistance but not in resistance to ethanol or osmotic shock. Interestingly, S. aureus acquired increased acid resistance when preincubated at a sublethal pH 4 prior to exposure to a lethal pH 2. This acid-adaptive response resulting in tolerance was mediated via sigB. However, ςB was not vital for the starvation-survival or recovery mechanisms. ςB does not have a major role in the expression of the global regulator of virulence determinant biosynthesis, staphylococcal accessory regulator (sarA), the production of a number of representative virulence factors, and pathogenicity in a mouse subcutaneous abscess model. However, SarA upregulates sigB expression in a growth-phase-dependent manner. Thus, ςB expression is linked to the processes controlling virulence determinant production. The role of ςB as a major regulator of the stress response, but not of starvation-survival, is discussed. PMID:9829915

  18. Root cap-dependent gravitropic U-turn of maize root requires light-induced auxin biosynthesis via the YUC pathway in the root apex.

    PubMed

    Suzuki, Hiromi; Yokawa, Ken; Nakano, Sayuri; Yoshida, Yuriko; Fabrissin, Isabelle; Okamoto, Takashi; Baluška, František; Koshiba, Tomokazu

    2016-08-01

    Gravitropism refers to the growth or movement of plants that is influenced by gravity. Roots exhibit positive gravitropism, and the root cap is thought to be the gravity-sensing site. In some plants, the root cap requires light irradiation for positive gravitropic responses. However, the mechanisms regulating this phenomenon are unknown. We herein report that maize roots exposed to white light continuously for ≥1-2h show increased indole-3-acetic acid (IAA) levels in the root tips, especially in the transition zone (1-3mm from the tip). Treatment with IAA biosynthesis inhibitors yucasin and l-kynurenine prevented any increases in IAA content and root curvature under light conditions. Analyses of the incorporation of a stable isotope label from tryptophan into IAA revealed that some of the IAA in roots was synthesized in the root apex. Furthermore, Zmvt2 and Zmyuc gene transcripts were detected in the root apex. One of the Zmyuc genes (ZM2G141383) was up-regulated by light irradiation in the 0-1mm tip region. Our findings suggest that IAA accumulation in the transition zone is due to light-induced activation of Zmyuc gene expression in the 0-1mm root apex region. Light-induced changes in IAA levels and distributions mediate the maize root gravitropic U-turn. PMID:27307546

  19. Root cap-dependent gravitropic U-turn of maize root requires light-induced auxin biosynthesis via the YUC pathway in the root apex

    PubMed Central

    Suzuki, Hiromi; Yokawa, Ken; Nakano, Sayuri; Yoshida, Yuriko; Fabrissin, Isabelle; Okamoto, Takashi; Baluška, František; Koshiba, Tomokazu

    2016-01-01

    Gravitropism refers to the growth or movement of plants that is influenced by gravity. Roots exhibit positive gravitropism, and the root cap is thought to be the gravity-sensing site. In some plants, the root cap requires light irradiation for positive gravitropic responses. However, the mechanisms regulating this phenomenon are unknown. We herein report that maize roots exposed to white light continuously for ≥1–2h show increased indole-3-acetic acid (IAA) levels in the root tips, especially in the transition zone (1–3mm from the tip). Treatment with IAA biosynthesis inhibitors yucasin and l-kynurenine prevented any increases in IAA content and root curvature under light conditions. Analyses of the incorporation of a stable isotope label from tryptophan into IAA revealed that some of the IAA in roots was synthesized in the root apex. Furthermore, Zmvt2 and Zmyuc gene transcripts were detected in the root apex. One of the Zmyuc genes (ZM2G141383) was up-regulated by light irradiation in the 0–1mm tip region. Our findings suggest that IAA accumulation in the transition zone is due to light-induced activation of Zmyuc gene expression in the 0–1mm root apex region. Light-induced changes in IAA levels and distributions mediate the maize root gravitropic U-turn. PMID:27307546

  20. Bone Marrow Minimal Residual Disease Was an Early Response Marker and a Consistent Independent Predictor of Survival After Anti-GD2 Immunotherapy

    PubMed Central

    Cheung, Nai-Kong V.; Ostrovnaya, Irina; Kuk, Deborah; Cheung, Irene Y.

    2015-01-01

    Purpose Immunotherapy is a standard of care for children with high-risk neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early response markers of minimal residual disease (MRD) in the BM that are also predictive of survival could help individualize patient therapies. Patients and Methods After achieving first remission (n = 163), primary refractory disease (n = 102), or second remission (n = 95), children with stage 4 neuroblastoma received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B, CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic variables were tested in both univariable and multivariable analyses, and MRD markers were further assessed individually and in combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum: 0 to 4) using the Cox regression models, and their predictive accuracy was determined by the concordance index. Results When BM was evaluated after cycle 2, individual markers were highly predictive of PFS and OS. The prediction accuracy improved when they were combined in postMRDSum. A multivariable model taking into account all the variables significant in the univariable analyses identified postMRDSum to be independently predictive of PFS and OS. When the model for OS also included missing killer immunoglobulin-like receptor ligand, human antimouse antibody response, and the enrollment disease status, the concordance index was 0.704. Conclusion BM MRD after two cycles of immunotherapy was confirmed as an early response marker and a consistent independent predictor of survival. PMID:25559819

  1. Influence of the Plant Defense Response to Escherichia coli O157:H7 Cell Surface Structures on Survival of That Enteric Pathogen on Plant Surfaces

    PubMed Central

    Seo, Suengwook

    2012-01-01

    Consumption of fresh and fresh-cut fruits and vegetables contaminated with Escherichia coli O157:H7 has resulted in hundreds of cases of illness and, in some instances, death. In this study, the influence of cell surface structures of E. coli O157:H7, such as flagella, curli fimbriae, lipopolysaccharides, or exopolysaccharides, on plant defense responses and on survival or colonization on the plant was investigated. The population of the E. coli O157:H7 ATCC 43895 wild-type strain was significantly lower on wild-type Arabidopsis plants than that of the 43895 flagellum-deficient mutant. The population of the E. coli O157:H7 43895 flagellum mutant was greater on both wild-type and npr1-1 mutant (nonexpressor of pathogenesis-related [PR] genes) plants and resulted in less PR gene induction, estimated based on a weak β-glucuronidase (GUS) signal, than did the 43895 wild-type strain. These results suggest that the flagella, among the other pathogen-associated molecular patterns (PAMPs), made a substantial contribution to the induction of plant defense response and contributed to the decreased numbers of the E. coli O157:H7 ATCC 43895 wild-type strain on the wild-type Arabidopsis plant. A curli-deficient E. coli O157:H7 86-24 strain survived better on wild-type Arabidopsis plants than the curli-producing wild-type 86-24 strain did. The curli-deficient E. coli O157:H7 86-24 strain exhibited a GUS signal at a level substantially lower than that of the curli-producing wild-type strain. Curli were recognized by plant defense systems, consequently affecting bacterial survival. The cell surface structures of E. coli O157:H7 have a significant impact on the induction of differential plant defense responses, thereby impacting persistence or survival of the pathogen on plants. PMID:22706044

  2. CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers

    PubMed Central

    Lv, Wei-Fu; Cheng, De-Lei; Zhou, Chun-Ze; Ni, Ming; Lu, Dong

    2015-01-01

    Objective To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). Materials and Methods Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. Results Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a ≥ 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a < 21.5% decrease (p < 0.001). Conclusion Computed tomography perfusion imaging can predict the early response to TACLI and survival of patients with CRLM. The percentage change in HAP after TACLI with a cutoff value of -21.5% is the optimal predictor. PMID:26175580

  3. Modeling the concentration-response function of the herbicide dinoseb on Daphnia magna (survival time, reproduction) and Pseudokirchneriella subcapitata (growth rate).

    PubMed

    Chèvre, Nathalie; Brazzale, Alessandra R; Becker-van Slooten, Kristin; Behra, Renata; Tarradellas, Joseph; Guettinger, Herbert

    2005-09-01

    Models describing dose-response relationships are becoming increasingly popular in ecotoxicology. They allow simple and thorough evaluations of toxicity test results, including inter- and extrapolations to concentrations or exposure times other than those tested. Simple parametric regression models are of particular interest because their parameters may be attributed mechanistic meanings and they can be applied without sophisticated mathematical and computational support. We recently proposed a four-parameter logistic regression model to fit the survival data of Daphnia magna under dinoseb stress. The model parameters are the maximum survival time, the minimum time required for an individual to die, effect concentration, EC(50), and a curve shape parameter. This model has now been applied to compare the lethality and reproduction toxicity of D. magna and the growth inhibition of Pseudokirchneriella subcapitata under dinoseb stress. It can be fitted adequately to all the measured data and the parameters can be attributed biological meanings in any of the three endpoints. A comparison of the modeled concentration-response functions of all three endpoints for dinoseb toxicity shows that the range of ECs with respect to both D. magna and algae is steep (a decrease of between 0.1 and 0.6 mg/L). The survival and reproduction of D. magna exhibit similar characteristic concentration-response functions and toxicities. The statistical no-effect concentration (SNEC) is 0.14 (survival) and 0.11 (reproduction)mg/L, respectively. On the other hand, algae seem to be less sensitive to dinoseb than D. magna (SNEC: 0.48 mg/L). However, further investigations of individual algae may lead to a more suitable comparison. We speculate that the four parameters of the model function can be related to specific properties of chemicals and organisms. Characterization of these properties would allow simple and appropriate estimation of the toxic effects of these chemicals. PMID:15978287

  4. Females increase reproductive investment in response to helper-mediated improvements in allo-feeding, nest survival, nestling provisioning and post-fledging survival in the Karoo scrub-robin Cercotrichas coryphaeus

    USGS Publications Warehouse

    Lloyd, P.; Andrew, Taylor W.; Du Plessis, M.A.; Martin, T.E.

    2009-01-01

    In many cooperatively-breeding species, the presence of one or more helpers improves the reproductive performance of the breeding pair receiving help. Helper contributions can take many different forms, including allo-feeding, offspring provisioning, and offspring guarding or defence. Yet, most studies have focussed on single forms of helper contribution, particularly offspring provisioning, and few have evaluated the relative importance of a broader range of helper contributions to group reproductive performance. We examined helper contributions to multiple components of breeding performance in the Karoo scrub-robin Cercotrichas coryphaeus, a facultative cooperative breeder. We also tested a prediction of increased female investment in reproduction when helpers improve conditions for rearing young. Helpers assisted the breeding male in allo-feeding the incubating female, increasing allo-feeding rates. Greater allo-feeding correlated with greater female nest attentiveness during incubation. Nest predation was substantially lower among pairs breeding with a helper, resulting in a 74% increase in the probability of nest survival. Helper contributions to offspring provisioning increased nestling feeding rates, resulting in a reduced incidence of nestling starvation and increased nestling mass. Nestling mass had a strong, positive effect on post-fledging survival. Controlling for female age and habitat effects, annual production of fledged young was 130% greater among pairs breeding with a helper, and was influenced most strongly by helper correlates with nest survival, despite important helper effects on offspring provisioning. Females breeding with a helper increased clutch size, supporting the prediction of increased female investment in reproduction in response to helper benefits. ?? 2009 J. Avian Biol.

  5. Photo-sensible (thymine containing) azo-polysiloxanes: synthesis and light induced effects

    NASA Astrophysics Data System (ADS)

    Enea, R.; Apostol, I.; Damian, V.; Hurduc, N.; Iordache, I.

    2008-03-01

    . The paper presents the possibility to obtain azo-polysiloxanes modified with thymine and their light induced processing with potential interest in opto-electronics or biomolecules nanomanipulation. The presence of the thymine group in the polymeric structure can confer to material biological properties, in the same time the capacity of tymine to generate H-bonds being useful to the relief geometry stabilization in time. The investigated polymers were obtained in a two step reaction, starting from a polysiloxane containing chlorobenzyl groups in the side chain. The azopolysiloxanes' photochromic behaviour was investigated in solid state, using thin films etalated on the surface of a quartz slide. The effect of surface relief structuration process under the action of UV (355 nm) laser radiation was studied. Laser induced effects on the material surface depends on the incident laser fluence and number of pulses.

  6. Flicker-light induced visual phenomena: frequency dependence and specificity of whole percepts and percept features.

    PubMed

    Allefeld, Carsten; Pütz, Peter; Kastner, Kristina; Wackermann, Jiří

    2011-12-01

    Flickering light induces visual hallucinations in human observers. Despite a long history of the phenomenon, little is known about the dependence of flicker-induced subjective impressions on the flicker frequency. We investigate this question using Ganzfeld stimulation and an experimental paradigm combining a continuous frequency scan (1-50 Hz) with a focus on re-occurring, whole percepts. On the single-subject level, we find a high degree of frequency stability of percepts. To generalize across subjects, we apply two rating systems, (1) a set of complex percept classes derived from subjects' reports and (2) an enumeration of elementary percept features, and determine distributions of occurrences over flicker frequency. We observe a stronger frequency specificity for complex percept classes than elementary percept features. Comparing the similarity relations among percept categories to those among frequency profiles, we observe that though percepts are preferentially induced by particular frequencies, the frequency does not unambiguously determine the experienced percept. PMID:21123084

  7. Modeling of coherent ultrafast magneto-optical experiments: Light-induced molecular mean-field model

    SciTech Connect

    Hinschberger, Y.; Hervieux, P.-A.

    2015-12-28

    We present calculations which aim to describe coherent ultrafast magneto-optical effects observed in time-resolved pump-probe experiments. Our approach is based on a nonlinear semi-classical Drude-Voigt model and is used to interpret experiments performed on nickel ferromagnetic thin film. Within this framework, a phenomenological light-induced coherent molecular mean-field depending on the polarizations of the pump and probe pulses is proposed whose microscopic origin is related to a spin-orbit coupling involving the electron spins of the material sample and the electric field of the laser pulses. Theoretical predictions are compared to available experimental data. The model successfully reproduces the observed experimental trends and gives meaningful insight into the understanding of magneto-optical rotation behavior in the ultrafast regime. Theoretical predictions for further experimental studies are also proposed.

  8. Retinol Dehydrogenase (RDH12) Protects Photoreceptors from Light-induced Degeneration in Mice*S

    PubMed Central

    Maeda, Akiko; Maeda, Tadao; Imanishi, Yoshikazu; Sun, Wenyu; Jastrzebska, Beata; Hatala, Denise A.; Winkens, Huub J.; Hofmann, Klaus Peter; Janssen, Jacques J.; Baehr, Wolfgang; Driessen, Carola A.; Palczewski, Krzysztof

    2014-01-01

    RDH12 has been suggested to be one of the retinol dehydrogenases (RDH) involved in the vitamin A recycling system (visual cycle) in the eye. Loss of function mutations in the RDH12 gene were recently reported to be associated with autosomal recessive childhood-onset severe retinal dystrophy. Here we show that RDH12 localizes to the photoreceptor inner segments and that deletion of this gene in mice slows the kinetics of all-trans-retinal reduction, delaying dark adaptation. However, accelerated 11-cis-retinal production and increased susceptibility to light-induced photoreceptor apoptosis were also observed in Rdh12−/− mice, suggesting that RDH12 plays a unique, nonredundant role in the photoreceptor inner segments to regulate the flow of retinoids in the eye. Thus, severe visual impairments of individuals with null mutations in RDH12 may likely be caused by light damage1. PMID:17032653

  9. Combination of light-induced effect and gate bias stress in organic phototransistors

    NASA Astrophysics Data System (ADS)

    Liguori, R.; Sheets, W. C.; Bezzeccheri, E.; Facchetti, A.; Rubino, A.

    2016-05-01

    In this work, the photoresponse of pentacene-based thin film transistors fabricated with a photocurable polymer insulator was investigated under visible and ultraviolet illumination. A simple model was developed to distinguish a photoconductive and a photovoltaic effect, that is, a direct photocurrent and a current enhancement caused by a threshold voltage shift. The direction of the light-induced threshold translation is affected by measurement conditions (e.g. integration time and voltage range) and is related to the nature of the trap states, specifically those located in the pentacene film near the interface with the polymer. In particular, it was shown that, thanks to this phenomenon, the photosensitivity of the fabricated phototransistors could be modulated by the gate bias applied during illumination.

  10. Light-Induced Exciton Spin Hall Effect in van der Waals Heterostructures.

    PubMed

    Li, Yun-Mei; Li, Jian; Shi, Li-Kun; Zhang, Dong; Yang, Wen; Chang, Kai

    2015-10-16

    We propose a light-induced spin Hall effect for interlayer exciton gas in monolayer MoSe2-WSe2 van der Waals heterostructure. By applying two infrared, spatially varying laser beams coupled to the exciton internal states, a spin-dependent gauge potential on the exciton center-of-mass motion is induced. This gauge potential deflects excitons in different spin states towards opposite directions, leading to a finite spin current but vanishing mass current. In the Hall bar geometry, the spin-dependent deflection gives rise to spin-dependent chiral edge states with spin-velocity locking. The spin current and chiral edge states of the excitons can be detected by spatially resolved photoluminescence spectroscopy. PMID:26550894

  11. Tuning and Erasing Surface Wrinkles by Reversible Visible-Light-Induced Photoisomerization.

    PubMed

    Zong, Chuanyong; Zhao, Yan; Ji, Haipeng; Han, Xue; Xie, Jixun; Wang, Juanjuan; Cao, Yanping; Jiang, Shichun; Lu, Conghua

    2016-03-14

    Periodic wrinkling across different scales has received considerable attention because it not only represents structure failure but also finds wide applications. How to prevent wrinkling or create desired wrinkling patterns is non-trivial because the dynamic evolution of wrinkles is a highly nonlinear problem. Herein, we report a simple yet powerful method to dynamically tune and/or erase wrinkling patterns with visible light. The light-induced photoisomerization of azobenzene units in azopolymer films leads to stress release and consequently to the erasure of the wrinkles. The wrinkles in unexposed regions are also affected and oriented perpendicular to the exposed boundary during the stress reorganization. Theoretical models were developed to understand the dynamics of the reversible photoisomerization-induced wrinkle evolution. This method can be applied for designing functional materials/devices, for example, for the reversible optical writing/erasure of information as demonstrated here. PMID:26894439

  12. A tunable azine covalent organic framework platform for visible light-induced hydrogen generation

    NASA Astrophysics Data System (ADS)

    Vyas, Vijay S.; Haase, Frederik; Stegbauer, Linus; Savasci, Gökcen; Podjaski, Filip; Ochsenfeld, Christian; Lotsch, Bettina V.

    2015-09-01

    Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of water- and photostable 2D azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number of nitrogen atoms. The electronic and steric variations in the precursors are transferred to the resulting frameworks, thus leading to a progressively enhanced light-induced hydrogen evolution with increasing nitrogen content in the frameworks. Our results demonstrate that by the rational design of COFs on a molecular level, it is possible to precisely adjust their structural and optoelectronic properties, thus resulting in enhanced photocatalytic activities. This is expected to spur further interest in these photofunctional frameworks where rational supramolecular engineering may lead to new material applications.

  13. Light induced chemical vapour deposition of titanium oxide thin films at room temperature

    NASA Astrophysics Data System (ADS)

    Halary, E.; Benvenuti, G.; Wagner, F.; Hoffmann, P.

    2000-02-01

    High resolution patterned deposition of titania is achieved by light induced chemical vapour deposition (LICVD), by imaging a mask onto a glass substrate. A long pulse XeCl Excimer laser (308 nm) provides, by perpendicular irradiation, the energy to convert titanium tetraisopropoxide (TTIP) vapour into titanium dioxide films, in an oxygen atmosphere, on unheated glass substrates. The amorphous titania deposits contain about 6% carbon contamination according to X-ray photoelectron spectroscopy (XPS) measurements. The deposition rate increases with increasing laser fluence until a maximum value is reached, then remains constant over a wide range, and finally decreases with further fluence increase due to titania ablation or thermal effects. The film thickness increases linearly with the number of pulses after a nucleation period. The strong influence of the laser pulse repetition rate on the growth rate and the thickness profile are reported.

  14. Light-induced effects-impacts to module performance measurements and reliability testing: An overview

    NASA Technical Reports Server (NTRS)

    Wronski, C. R.

    1985-01-01

    The stability of solar cells is a key factor in determining the reliability of photovoltaic modules and is of great interest in the case of solar cells having a new technology which has not yet been fully developed. In particular this question arises with hydrogenated amorphous silicon (a-Si) solar cells because a-Si exhibits reversible light induced changes in its electronic properties, commonly referred to as the Staebler-Wronski effect (SWE). Continuous progress is being made in the peak conversion efficiencies of a-Si solar cells and efficiencies in excess of 11% have been achieved. However, stability is still a problem. ARCO Solar reports results on solar cells which, after over a year's exposure to sunlight, under open circuit conditions, still have about 7% conversion efficiency. Other results show a region of fast degradation for about a month, after which the degradation diminishes rapidly.

  15. High efficiency light-induced dielectrophoresis biochip prepared using CVD techniques.

    PubMed

    Wu, Hung-Wei; Huang, Yao-Sheng; Lee, Hsin-Ying; Tsai, Wu-Han; Chen, Kuan-Yu; Jian, Li-Yi

    2016-10-01

    This article describes a high-efficiency light-induced dielectrophoresis biochip containing a thin film prepared through inductively coupled plasma chemical vapor deposition (ICPCVD). The biochip comprises two ITO glass substrates and a photoconductive amorphous silicon thin film. The biochip can effectively sort particular particles (or cells) by projecting visible light onto the surface of the silicon thin film. The sorting efficiency of biochips is highly associated with the quality of the deposited amorphous silicon thin films; therefore, the choice of deposition technique is extremely critical. However, no study has examined this problem. Hence, the current study thoroughly compared the efficiency of the biochip when films produced through plasma-enhanced chemical vapor deposition and ICPCVD are used. PMID:27530346

  16. Light-induced atomic desorption for loading a sodium magneto-optical trap

    SciTech Connect

    Telles, Gustavo; Ishikawa, Tetsuya; Gibbs, Matthew; Raman, Chandra

    2010-03-15

    We report studies of photon-stimulated desorption, also known as light-induced atomic desorption, of sodium atoms from a vacuum-cell glass surface used for loading a magneto-optical trap (MOT). Fluorescence detection was used to record the trapped atom number and the desorption rate. We observed a steep wavelength dependence of the desorption process above 2.6 eV photon energy, a result significant for estimations of sodium vapor density in the lunar atmosphere. Our data fit well to a simple model for the loading of the MOT dependent only on the sodium desorption rate and residual gas density. Up to 3.7x10{sup 7} Na atoms were confined under ultrahigh-vacuum conditions, creating promising loading conditions for a vapor-cell-based atomic Bose-Einstein condensate of sodium.

  17. Visible Light-Induced Photoredox Construction of Trifluoromethylated Quaternary Carbon Centers from Trifluoromethylated Tertiary Bromides.

    PubMed

    Huan, Feng; Chen, Qing-Yun; Guo, Yong

    2016-08-19

    A mild, operationally simple, visible light-induced photoredox method for constructing novel trifluoromethylated quaternary carbon centers from trifluoromethylated tertiary bromides has been developed. Using this method, a wide range of alkenes were successfully bifunctionalized to γ-butyrolactams. As for electron-rich alkenes, reactions catalyzed by Ir(dF(CF3)ppy)2(dtbbpy)(PF6) were kinetic processes with high yields and short times. For styrenes, reactions catalyzed by Ir(ppy)2(dtbbpy)(PF6) were thermodynamic processes with moderate yields and prolonged reaction times. For aliphatic alkenes, the reactions were neither thermodynamic nor kinetic and fac-Ir(ppy)3 was used as catalyst. Thus, reactions were not as efficient as electron-rich alkenes. The atom-transfer radical addition reactions of trifluoromethylated tertiary bromides with alkynes were also achieved. The configuration of products we separated was E type only. Some of the products exhibited bactericidal activity. PMID:27438228

  18. Experimental studies of collective excitations of a BEC in light-induced gauge fields

    NASA Astrophysics Data System (ADS)

    Li, Chuan-Hsun; Niffenegger, Robert; Blasing, David; Olson, Abraham; Chen, Yong P.

    2015-05-01

    We present our experimental studies of collective modes including spin dipole mode and scissors mode of a 87Rb Bose-Einstein condensate (BEC) in the presence of Raman light-induced gauge fields and synthetic spin-orbit coupling (SOC). By Raman dressing the mf spin states within the F =1 manifold, we engineer atoms' energy-momentum dispersion to create synthetic SOC, and spin dependent synthetic electric and magnetic fields. We have used spin dependent synthetic electric fields to make two BECs with different spins oscillate and collide in the optical trap. We have studied the effects of SOC on both the momentum damping and thermalization behaviors of the BECs when undergoing such spin dipole oscillations. We have also used spatially dependent synthetic electric fields to excite the scissors mode, which has been used as a probe for superfluidity. We have investigated the effects of the synthetic gauge fields and SOC on the measured scissors mode.

  19. Light-induced surface graft polymerizations initiated by an anthraquinone dye on cotton fibers.

    PubMed

    Zhuo, Jingyuan; Sun, Gang

    2014-11-01

    Anthraquinone and its derivatives could serve as photo-sensitizers and generate radicals and reactive oxygen species in polymers under exposure of UVA or day light. Such a property was utilized in development of novel light-induced surface radical graft polymerizations on cotton fibers that were dyed with an anthraquinone derivative, 2-ethylanthraquinone. Several functional monomers were directly grafted onto the dyed cotton fibers upon UVA exposure. The chemical and morphological structures and thermal properties of the grafted fibers were confirmed and characterized by Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM) and thermal gravimetric analysis (TGA). Reaction conditions including concentrations of the photosensitizer, the amount of monomers, as well as UVA irradiation time could influence grafting efficiencies. More interestingly, the surface graft polymerization did not significantly change the light active functions of the agent, evidenced by the light-active antimicrobial functions of the grafted fibers. PMID:25129730

  20. Light-induced point defect reactions of residual iron in crystalline silicon after aluminum gettering

    SciTech Connect

    Abdelbarey, D.; Kveder, V.; Schroeter, W.; Seibt, M.

    2010-08-15

    Deep level transient spectroscopy is used to study light-induced reactions of residual iron impurities after aluminum gettering (AlG) in crystalline silicon. White-light illumination at room temperature leads to the formation of a defect which is associated with a donor level at 0.33 eV above the valence band. This defect is stable up to about 175 deg. C where it dissociates reversibly in case of small iron concentrations and irreversibly for high iron concentrations. Since marker experiments using gold and platinum diffusion show a high vacancy concentration after AlG a tentative identification of the new defect as the metastable iron-vacancy pair is proposed.

  1. Light-induced atomic desorption in a compact system for ultracold atoms

    PubMed Central

    Torralbo-Campo, Lara; Bruce, Graham D.; Smirne, Giuseppe; Cassettari, Donatella

    2015-01-01

    In recent years, light-induced atomic desorption (LIAD) of alkali atoms from the inner surface of a vacuum chamber has been employed in cold atom experiments for the purpose of modulating the alkali background vapour. This is beneficial because larger trapped atom samples can be loaded from vapour at higher pressure, after which the pressure is reduced to increase the lifetime of the sample. We present an analysis, based on the case of rubidium atoms adsorbed on pyrex, of various aspects of LIAD that are useful for this application. Firstly, we study the intensity dependence of LIAD by fitting the experimental data with a rate-equation model, from which we extract a correct prediction for the increase in trapped atom number. Following this, we quantify a figure of merit for the utility of LIAD in cold atom experiments and we show how it can be optimised for realistic experimental parameters. PMID:26458325

  2. Low-intensity light induces vasorelaxation: a study for possible mechanism

    NASA Astrophysics Data System (ADS)

    Morimoto, Yuji; Matsuo, Hirotaka; Arai, Tsunenori; Kikuchi, Makoto

    1996-05-01

    To investigate the mechanism of light induced vasorelaxation, vascular tension change in normal buffer solution was compared with that in the buffer containing either the following drug: (1) guanylate cyclase inhibitor; (2) nitric oxide synthetase inhibitors and the optical isomers; and (3) vasodilating agent. The vasorelaxation caused by ultraviolet light irradiation was independent of the presence of an intact endothelium. It was inhibited by methyleneblue, but not influenced by either L-NMMA or D-NMMA. On the other hand, this vasorelaxation was enhanced by the agents containing nitro group (L-NAME, D-NAME) or sodium nitrite. These results show that the light activates guanylate cyclase, which results in the vasorelaxation. This activation was reinforced by the agents containing nitro group. We conclude that primary photochemical product, which is probably nitric oxide originated from photodissociation of nitro groups, may produce the vasorelaxation. The preliminary investigation suggests that ultraviolet irradiation may be benefit in the treatment for vasospasm.

  3. DNA Photonics — Probing Light-Induced Dynamics in DNA on the Femtosecond Timescale

    NASA Astrophysics Data System (ADS)

    Wang, Qiang; Fiebig, Torsten

    In Chap. 10, Wang and Fiebig discuss about a new field, DNA photonics that is important to understand the role of DNA as a functional building block in molecular nanoscale devices, and is also expected to shed light on the complex interactions between structural and electronic properties of DNA. The latter is important for biomedical applications such as DNA-targeted drug design. In this chapter, the authors present experimental data from several different classes of functionalized DNA systems and illustrate the relationship between the structural dynamics and charge injection/migration using state-of-the art femtosecond broadband spectroscopy. They also highlight the importance of the initial electronic excitation for modelling electron transfer rates and point out that ultrafast electronic energy migration, dissipation, and (de)localization must be included into the theoretical description of light-induced dynamics in DNA.

  4. Light-Induced Solubility Modulation of Polyfluorene To Enhance the Performance of OLEDs.

    PubMed

    Schelkle, Korwin M; Bender, Markus; Jeltsch, Krischan; Buckup, Tiago; Müllen, Klaus; Hamburger, Manuel; Bunz, Uwe H F

    2015-11-23

    Liquid-phase processing is a key prerequisite for the cost-efficient fabrication of organic electronic devices. We report an approach for light-induced modulation of the solubility of π-conjugated polymers (polyfluorene) with side chains functionalized with hydroxycinnamic acid. Irradiation with light cleaves the solubilizing side chains and renders the thin films of the polyfluorene insoluble. In a proof of concept device, polyfluorenes were applied as emissive layers in OLEDs. Photoirradiation of the emission layer leads to an increase in OLED performance combined with a modulation of the solubility of the thin film. These results offer the possibility for further development in terms of manipulating the solubility and emissive parameters of an important class of functional materials. PMID:26463263

  5. Light-induced fluorescence endoscopy (LIFE) imaging system for early cancer detection

    NASA Astrophysics Data System (ADS)

    Zeng, Haishan; MacAulay, Calum E.; Lam, Stephen; Palcic, Branko

    1999-09-01

    This paper summarizes our experiences on the development of a Light Induced Fluorescence Endoscopy (LIFE) imaging system for early cancer detection in the respiratory and gastrointestinal tract. The system utilizes tissue autofluorescence to provide real time video imaging of the examined organ. No exogenous fluorescent tumor markers are needed. It is used by a physician in adjunct to conventional white-light endoscopy. Suspicious areas are identified in pseudo color to guide biopsy. A multi- center clinical trial has demonstrated that in the lung, the relative sensitivity of white-light imaging + LIFE imaging vs. white-light imaging alone was 6.3 for intraepithelial neoplastic lesion detection and 2.71 when invasive carcinomas were also included. The following issues will be discussed: (1) spectroscopy study design for imaging system development; (2) architecture of the imaging systems; (3) different imaging modalities (white-light imaging, dual channel fluorescence imaging, and combined fluorescence/reflectance imaging); and (4) clinical applications.

  6. A tunable azine covalent organic framework platform for visible light-induced hydrogen generation

    PubMed Central

    Vyas, Vijay S.; Haase, Frederik; Stegbauer, Linus; Savasci, Gökcen; Podjaski, Filip; Ochsenfeld, Christian; Lotsch, Bettina V.

    2015-01-01

    Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of water- and photostable 2D azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number of nitrogen atoms. The electronic and steric variations in the precursors are transferred to the resulting frameworks, thus leading to a progressively enhanced light-induced hydrogen evolution with increasing nitrogen content in the frameworks. Our results demonstrate that by the rational design of COFs on a molecular level, it is possible to precisely adjust their structural and optoelectronic properties, thus resulting in enhanced photocatalytic activities. This is expected to spur further interest in these photofunctional frameworks where rational supramolecular engineering may lead to new material applications. PMID:26419805

  7. In search of the pathways for light-induced pacemaker resetting in the suprachiasmatic nucleus.

    PubMed

    Meijer, Johanna H; Schwartz, William J

    2003-06-01

    Within the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is a circadian pacemaker that functions as a clock. Its endogenous period is adjusted to the external 24-h light-dark cycle, primarily by light-induced phase shifts that reset the pacemaker's oscillation. Evidence using a wide variety of neurobiological and molecular genetic tools has elucidated key elements that comprise the visual input pathway for SCN photoentrainment in rodents. Important questions remain regarding the intracellular signals that reset the autoregulatory molecular loop within photoresponsive cells in the SCN's retino-recipient subdivision, as well as the intercellular coupling mechanisms that enable SCN tissue to generate phase shifts of overt behavioral and physiological circadian rhythms such as locomotion and SCN neuronal firing rate. Multiple neurotransmitters, protein kinases, and photoinducible genes add to system complexity, and we still do not fully understand how dawn and dusk light pulses ultimately produce bidirectional, advancing and delaying phase shifts for pacemaker entrainment. PMID:12828281

  8. Evaluation of dental enamel caries assessment using Quantitative Light Induced Fluorescence and Optical Coherence Tomography.

    PubMed

    Maia, Ana Marly Araújo; de Freitas, Anderson Zanardi; de L Campello, Sergio; Gomes, Anderson Stevens Leônidas; Karlsson, Lena

    2016-06-01

    An in vitro study of morphological alterations between sound dental structure and artificially induced white spot lesions in human teeth, was performed through the loss of fluorescence by Quantitative Light-Induced Fluorescence (QLF) and the alterations of the light attenuation coefficient by Optical Coherence Tomography (OCT). To analyze the OCT images using a commercially available system, a special algorithm was applied, whereas the QLF images were analyzed using the software available in the commercial system employed. When analyzing the sound region against white spot lesions region by QLF, a reduction in the fluorescence intensity was observed, whilst an increase of light attenuation by the OCT system occurred. Comparison of the percentage of alteration between optical properties of sound and artificial enamel caries regions showed that OCT processed images through the attenuation of light enhanced the tooth optical alterations more than fluorescence detected by QLF System. QLF versus OCT imaging of enamel caries: a photonics assessment. PMID:26351155

  9. Light-induced atomic desorption in a compact system for ultracold atoms.

    PubMed

    Torralbo-Campo, Lara; Bruce, Graham D; Smirne, Giuseppe; Cassettari, Donatella

    2015-01-01

    In recent years, light-induced atomic desorption (LIAD) of alkali atoms from the inner surface of a vacuum chamber has been employed in cold atom experiments for the purpose of modulating the alkali background vapour. This is beneficial because larger trapped atom samples can be loaded from vapour at higher pressure, after which the pressure is reduced to increase the lifetime of the sample. We present an analysis, based on the case of rubidium atoms adsorbed on pyrex, of various aspects of LIAD that are useful for this application. Firstly, we study the intensity dependence of LIAD by fitting the experimental data with a rate-equation model, from which we extract a correct prediction for the increase in trapped atom number. Following this, we quantify a figure of merit for the utility of LIAD in cold atom experiments and we show how it can be optimised for realistic experimental parameters. PMID:26458325

  10. Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.

    PubMed

    Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

    2016-01-01

    Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias - decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis. PMID:27240733

  11. Theory of light-induced effective magnetic field in Rashba ferromagnets

    NASA Astrophysics Data System (ADS)

    Qaiumzadeh, Alireza; Titov, Mikhail

    2016-07-01

    Motivated by recent experiments on all-optical magnetization reversal in conductive ferromagnetic thin films we use nonequilibrium formalism to calculate the effective magnetic field induced in a Rashba ferromagnet by a short laser pulse. The main contribution to the effect originates in the direct optical transitions between spin-split subbands. The resulting effective magnetic field is inversely proportional to the impurity scattering rate and can reach the amplitude of a few Tesla in the systems like Co/Pt bilayers. We show that the total light-induced effective magnetic field in ferromagnetic systems is the sum of two contributions: a helicity dependent term, which is an even function of magnetization, and a helicity independent term, which is an odd function of magnetization. The primary role of the spin-orbit interaction is to widen the frequency range for direct optical transitions.

  12. A tunable azine covalent organic framework platform for visible light-induced hydrogen generation.

    PubMed

    Vyas, Vijay S; Haase, Frederik; Stegbauer, Linus; Savasci, Gökcen; Podjaski, Filip; Ochsenfeld, Christian; Lotsch, Bettina V

    2015-01-01

    Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of water- and photostable 2D azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number of nitrogen atoms. The electronic and steric variations in the precursors are transferred to the resulting frameworks, thus leading to a progressively enhanced light-induced hydrogen evolution with increasing nitrogen content in the frameworks. Our results demonstrate that by the rational design of COFs on a molecular level, it is possible to precisely adjust their structural and optoelectronic properties, thus resulting in enhanced photocatalytic activities. This is expected to spur further interest in these photofunctional frameworks where rational supramolecular engineering may lead to new material applications. PMID:26419805

  13. Immobilization of the nematode Caenorhabditis elegans with addressable light-induced heat knockdown (ALINK).

    PubMed

    Chuang, Han-Sheng; Chen, Hsiang-Yu; Chen, Chang-Shi; Chiu, Wen-Tai

    2013-08-01

    Caenorhabditis (C.) elegans is a model animal used in genetics, neuroscience, and developmental biology. Researchers often immobilize squirming worms to obtain high-quality images for analysis. However, current methods usually require physical contact or anesthetics. This can cause injuries to worm bodies or neuron disturbances. This study presents an alternative technique, called addressable light-induced heat knockdown (ALINK), to effectively immobilize worms by using light-induced sublethal heat. A microchip composed of an indium-tin-oxide (ITO) glass plate and an ITO glass plate coated with a photoconductive layer (a-Si:H) was produced. Worms to be immobilized were immersed in a liquid medium and sandwiched between the two plates. When the worms were irradiated with a focused laser beam in the presence of electric fields (referred to as an optoelectric treatment), the optoelectric effect heated the liquid medium. The neural functions of the worms shut down temporarily when a critical temperature (>31 °C) was reached. Their neural functions resumed after the heat source was removed. A temperature above 37 °C killed all worms. Using short-wavelength light reduced the worms' recovery time. An equivalent circuit was modeled to predict the operating modes, and an optoelectric treatment with a high-concentration medium enhanced rapid heating. A safe operating range (20 Vpp (peak-to-peak voltage), 100 kHz to 10 MHz, 31 to 37 °C) to induce heat knockdown (KD) was also investigated. The results show that the heat KD was well controlled, autonomous, and reversible. This technique can be used for worm immobilization. PMID:23719845

  14. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

    PubMed Central

    Moriwaki, Toshikazu; Yamamoto, Yoshiyuki; Gosho, Masahiko; Kobayashi, Mariko; Sugaya, Akinori; Yamada, Takeshi; Endo, Shinji; Hyodo, Ichinosuke

    2016-01-01

    Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS). Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated. Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents. Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development. PMID:27031848

  15. Coherent spin-light-induced mechanisms in the semirelativistic limit of the self-consistent Dirac-Maxwell equations

    NASA Astrophysics Data System (ADS)

    Hinschberger, Y.; Manfredi, G.; Hervieux, P.-A.

    2016-04-01

    We present a self-consistent mean-field model based on a two-component Pauli-like equation that incorporates quantum and relativistic effects (up to second order in 1 /c ) for both external and internal electromagnetic fields. By taking the semirelativistic limit of the Dirac-Maxwell equations in the presence of an external electromagnetic field we obtain an analytical expression of a coherent light-induced mean-field Hamiltonian. The latter exhibits several mechanisms that involve the internal mean fields created by all the electrons and the external electromagnetic field (laser). The role played by the light-induced current density and the light-induced second-order charge density acting as sources in Maxwell's equations are clarified. In particular, we identify clearly four different mechanisms involving the spins that may play an important role in coherent ultrafast spin dynamics.

  16. Survival of Patients with Hepatocellular Carcinoma (HCC) Treated by Percutaneous Radio-Frequency Ablation (RFA) Is Affected by Complete Radiological Response

    PubMed Central

    Cabibbo, Giuseppe; Maida, Marcello; Genco, Chiara; Alessi, Nicola; Peralta, Marco; Butera, Giuseppe; Galia, Massimo; Brancatelli, Giuseppe; Genova, Claudio; Raineri, Maurizio; Orlando, Emanuele; Attardo, Simona; Giarratano, Antonino; Midiri, Massimo; Di Marco, Vito; Craxì, Antonio; Cammà, Calogero

    2013-01-01

    Background Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. Aim To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. Methods A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. Results The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR. The proportion of major complications after treatment was 4%. Conclusions RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival. PMID:23922893

  17. The Stringent Response Mediated by (p)ppGpp Is Required for Virulence of Pseudomonas syringae pv. tomato and Its Survival on Tomato.

    PubMed

    Chatnaparat, Tiyakhon; Li, Zhong; Korban, Schuyler S; Zhao, Youfu

    2015-07-01

    The hypersensitive response and pathogenicity (hrp) type III secretion system (T3SS) is a key pathogenicity factor in Pseudomonas syringae pv. tomato DC3000 (DC3000). In this study, the role of the second messenger (p)ppGpp on virulence and survival of DC3000 was investigated. Results have demonstrated that (p)ppGpp-deficient mutant (ppGpp(0)) of DC3000 exhibited lower levels of expression of the T3SS and genes of other virulence traits, such as coronatine toxin. The ppGpp(0) mutant of DC3000 was greatly impaired in causing disease and in growth in planta. Furthermore, (p)ppGpp was required for swarming motility, pyoverdine production, the oxidative stress response, as well as γ-amino butyric acid utilization. Screening of amino acids, major signals in activation of ppGpp biosynthesis, revealed that promoter activities of the avrPto gene could be either activated or suppressed by various amino acids in a ppGpp-dependent or -independent manner. Moreover, the ppGpp(0) mutant exhibited increased cell size and decreased survival on plant surfaces. Altogether, these findings indicate that ppGpp acts as an internal signal that regulates the T3SS as well as other virulence factors in pseudomonads and suggest that bacterial pathogens utilize intracellular messengers to sense environmental and nutritional signals for rapid, precise, and reversible control of their pathogenesis and survival. PMID:25675257

  18. Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma

    PubMed Central

    Horvat, Mateja; Novakovic, Barbara Jezersek

    2010-01-01

    Background The introduction of rituximab into the treatment of patients with non-Hodgkin’s lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relationship between either the quality of the response or the line of the rituximab treatment and the overall survival (OS) as well as the disease-free survival (DFS) of patients with B-cell lymphomas. Patients and methods. In the study, we analysed treatment outcomes in patients with different histological types of B-cell lymphomas who were treated at the Institute of Oncology between 2003 and 2007 with rituximab and chemotherapy. We included only patients who had the level of CD20 expression assessed prior to the introduction of the treatment with quantitative flow-cytometric measurements. The OS and DFS were evaluated by Kaplan-Meier survival curves. Results One hundred and fourteen patients were enrolled in the study. Patients who achieved a complete response after the rituximab containing treatment had a significantly longer OS than those reaching a partial response (hazard ratio [HR], 0.34; 95% CI, 0.05 to 0.91, P = 0.0375) and than patients with stable (hazard ratio [HR], 0.11; 95% CI, 0.0002 to 0.033, P < 0.0001) or progressive disease (hazard ratio [HR], 0.09; 95% CI, 0.003 to 0.03, P < 0.0001). Patients who achieved a complete response (CR; n = 70; 61.4%) had also a significantly longer DFS (hazard ratio [HR], 0.26; 95% CI, 0.021 to 0.538, P = 0.0068) than those reaching only a partial response (PR; n = 17; 14.9%). Patients treated with rituximab as the first-line treatment (n = 50; 43.9%) had a significantly longer OS than those treated with rituximab for the first

  19. Coupled effects of director orientations and boundary conditions on light induced bending of monodomain nematic liquid crystalline polymer plates

    NASA Astrophysics Data System (ADS)

    You, Yue; Xu, Changwei; Ding, Shurong; Huo, Yongzhong

    2012-12-01

    A photo-chromic liquid crystal polymers (LCPs) is a smart material for large light-activated variation or bending to transfer luminous energy into mechanical energy. We study the light induced behavior by modeling planar and homeotropic nematic network polymer plates. We effectively illustrate some reported experimental outcomes and theoretically predict some possible bending patterns. This paper constructs an understanding between the bending behaviors and interactions among the alignments, aspect ratios and boundary conditions, etc. Our work provides information on optimizing light induced bending in the process of micro-opto-mechanical system (MOMS) design.

  20. Effects of hydroxyl radical scavengers KCN and CO on ultraviolet light-induced activation of crude soluble guanylate cyclase

    SciTech Connect

    Karlsson, J.O.; Axelsson, K.L.; Andersson, R.G.

    1985-01-01

    The crude soluble guanylate cyclase (GC) from bovine mesenteric artery was stimulated by ultraviolet (UV) light (366 nm). Addition of free radical scavengers, dimethylsulfoxide or superoxide dismutase and/or catalase to the GC assay did not abolish the stimulatory effect of UV light. On the contrary, the UV light-induced activation was enhanced in the presence of these scavengers. KCN (1 mM) did not affect the UV light-induced activation, while 0.1 mM of CO potentiated the activation. These results may indicate that UV light is operating through a direct interaction with the ferrous form of the GC-heme.

  1. Formation of bioactive N-doped TiO2 on Ti with visible light-induced antibacterial activity using NaOH, hot water, and subsequent ammonia atmospheric heat treatment.

    PubMed

    Kawashita, Masakazu; Endo, Naoko; Watanabe, Tomoaki; Miyazaki, Toshiki; Furuya, Maiko; Yokota, Kotoe; Abiko, Yuki; Kanetaka, Hiroyasu; Takahashi, Nobuhiro

    2016-09-01

    Titanium (Ti) treated with NaOH and hot water, and heated in an ammmonia (NH3) gas atmosphere for 1 or 3h exhibited in vitro apatite formation within 7days when soaked in simulated body fluid (SBF). Moreover, the treated Ti decomposed methylene blue and showed excellent bactericidal activity against Escherichia coli under visible light irradiation. The surface treatment resulted in the formation of a fine network of N-doped anatase-type titania (TiO2-xNx) on the Ti surface, which was responsible for both the apatite formation in SBF and the visible light-induced antibacterial activity. These preliminary results highlight the efficacy of our simple method for producing novel bioactive Ti with visible light-induced antibacterial activity, which could be applied to orthopaedic and dental implants without the risk of infection. PMID:27208442

  2. Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)--novel predictors for response and survival in gastric cancer patients.

    PubMed

    Goekkurt, E; Hoehn, S; Wolschke, C; Wittmer, C; Stueber, C; Hossfeld, D K; Stoehlmacher, J

    2006-01-30

    To evaluate the predictive value of a panel of gene polymorphisms involved in metabolism of 5-FU and cisplatin on clinical outcome in advanced gastric cancer patients. A total of 52 patients were enrolled in this study. DNA was extracted from paraffin-embedded tumour specimen. Genotypes were determined using PCR-RFLP. Median survival time was 6.0 months (95% CI 3.9;8.1). Overall response rate was 26%. Patients possessing the glutathione S-transferase P1-105 Valine/Valine (GSTP1-105VV) genotype showed a response rate of 67% compared to 21% in patients harbouring at least one GSTP1-105 Isoleucine (GSTP1-105I) allele (P=0.038). GSTP1-105VV patients demonstrated a significant superior median survival time of 15.0 months (95% CI 7.8;22.0) compared to 6.0 months (95% CI 5.1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15.3) compared to 6.0 months (95% CI 5.0;7.0) in patients with unfavourable TS genotypes (P=0.099). Patients harbouring the GSTP1-105II genotype and one of the unfavourable TS genotypes showed an inferior median survival time of 6.0 months (95% CI 3.9;8.1) compared to 11 months (95% CI 6,23;15,77) in patients with either GSTP1-105VV or a favourable TS genotype (P=0.044). Testing for TS and GSTP1 polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy. PMID:16317430

  3. The natural killer cell response and tumor debulking are associated with prolonged survival in recurrent glioblastoma patients receiving dendritic cells loaded with autologous tumor lysates.

    PubMed

    Pellegatta, Serena; Eoli, Marica; Frigerio, Simona; Antozzi, Carlo; Bruzzone, Maria Grazia; Cantini, Gabriele; Nava, Sara; Anghileri, Elena; Cuppini, Lucia; Cuccarini, Valeria; Ciusani, Emilio; Dossena, Marta; Pollo, Bianca; Mantegazza, Renato; Parati, Eugenio A; Finocchiaro, Gaetano

    2013-03-01

    Recurrent glioblastomas (GBs) are highly aggressive tumors associated with a 6-8 mo survival rate. In this study, we evaluated the possible benefits of an immunotherapeutic strategy based on mature dendritic cells (DCs) loaded with autologous tumor-cell lysates in 15 patients affected by recurrent GB. The median progression-free survival (PFS) of this patient cohort was 4.4 mo, and the median overall survival (OS) was 8.0 mo. Patients with small tumors at the time of the first vaccination (< 20 cm(3); n = 8) had significantly longer PFS and OS than the other patients (6.0 vs. 3.0 mo, p = 0.01; and 16.5 vs. 7.0 mo, p = 0.003, respectively). CD8(+) T cells, CD56(+) natural killer (NK) cells and other immune parameters, such as the levels of transforming growth factor β, vascular endothelial growth factor, interleukin-12 and interferon γ (IFNγ), were measured in the peripheral blood and serum of patients before and after immunization, which enabled us to obtain a vaccination/baseline ratio (V/B ratio). An increased V/B ratio for NK cells, but not CD8(+) T cells, was significantly associated with prolonged PFS and OS. Patients exhibiting NK-cell responses were characterized by high levels of circulating IFNγ and E4BP4, an NK-cell transcription factor. Furthermore, the NK cell V/B ratio was inversely correlated with the TGFβ2 and VEGF V/B ratios. These results suggest that tumor-loaded DCs may increase the survival rate of patients with recurrent GB after effective tumor debulking, and emphasize the role of the NK-cell response in this therapeutic setting. PMID:23802079

  4. Biochemical and anatomical responses related to the in vitro survival of the tropical bromeliad Nidularium minutum to low temperatures.

    PubMed

    Carvalho, Camila Pereira; Hayashi, Adriana Hissae; Braga, Marcia Regina; Nievola, Catarina Carvalho

    2013-10-01

    Nidularium minutum is a tropical bromeliad that grows in natural environment with temperatures ranging from 2 to 30 °C. In the present work we cultivated this species in vitro at 5, 10, 15, and 25 °C for 3 and 6 months aiming at assessing biochemical and morphological responses that allow its survival under low temperatures. No survival was observed for plants cultured constantly at 5 °C and the lowest biometric parameters were found for those grown at 10 °C. A thick aquiferous parenchyma, accumulation of reducing sugars, and increased pectin content in the cell walls were observed in plants grown at 10 and 15 °C when compared to those maintained at 25 °C. In plants cultured at 10 °C, leaf bleaching correlated with low chlorophyll content and lower survival rate after 6 months when compared to those grown at 15 °C. The best in vitro culture condition for slow growth and plant acclimatization was found to be at 15 °C. This probably correlated with the immediate availability of carbon to restore growth during acclimatization and also with higher root initiation under this condition. This study brings information about the responses related to functional adaptation to low temperatures in N. minutum cultured in vitro that can also be implicated in its survival under natural conditions. Additionally, it suggests the best temperature to form a minimal growth collection to be used in restocking and conservation programs for endangered tropical bromeliads. PMID:23917072

  5. Redox regulation of cAMP-responsive element-binding protein and induction of manganous superoxide dismutase in nerve growth factor-dependent cell survival.

    PubMed

    Bedogni, Barbara; Pani, Giovambattista; Colavitti, Renata; Riccio, Antonella; Borrello, Silvia; Murphy, Mike; Smith, Robin; Eboli, Maria Luisa; Galeotti, Tommaso

    2003-05-01

    Reactive oxygen species (ROS) act as both signaling molecules and mediators of cell damage in the nervous system and are implicated in the pathogenesis of neurodegenerative diseases. Neurotrophic factors such as the nerve-derived growth factor (NGF) support neuronal survival during development and promote regeneration after neuronal injury through the activation of intracellular signals whose molecular effectors and downstream targets are still largely unknown. Here we present evidence that early oxidative signals initiated by NGF in PC12 cells, an NGF-responsive cell line, play a critical role in preventing apoptosis induced by serum deprivation. This redox-signaling cascade involves phosphatidylinositol 3-kinase, the small GTPase Rac-1, and the transcription factor cAMP-responsive element-binding protein (CREB), a molecule essential to promote NGF-dependent survival. We found that ROS are necessary for NGF-dependent phosphorylation of CREB, an event directly correlated with CREB activity, whereas hydrogen peroxide induces a robust CREB phosphorylation. Cells exposed to NGF show a late decrease in the intracellular content of ROS when compared with untreated cells and increased expression of the mitochondrial antioxidant enzyme manganese superoxide dismutase, a general inhibitor of cell death. Accordingly, serum deprivation-induced apoptosis was selectively inhibited by low concentrations of the mitochondrially targeted antioxidant Mito Q (mitoquinol/mitoquinone). Taken together, these data demonstrate that the oxidant-dependent activation of CREB is a component of NGF survival signaling in PC12 cells and outline an intriguing circuitry by which a cytosolic redox cascade promotes cell survival at least in part by increasing mitochondrial resistance to oxidative stress. PMID:12609977

  6. Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

    PubMed Central

    Zhu, Wenjie; Xu, Binghe

    2015-01-01

    Background Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT). Methods From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT. Results 166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001). Conclusions Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup. PMID:26291454

  7. The effect of Mycobacterium tuberculosis CRISPR-associated Cas2 (Rv2816c) on stress response genes expression, morphology and macrophage survival of Mycobacterium smegmatis.

    PubMed

    Huang, Qinqin; Luo, Hongping; Liu, Minqiang; Zeng, Jie; Abdalla, Abualgasim Elgaili; Duan, Xiangke; Li, Qiming; Xie, Jianping

    2016-06-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are present in the genome of 40% bacteria and 90% archaea. CRISPR and accompanying Cas proteins constitute an adaptive immune system against disruptive mobile genetic elements. Two CRISPRs and 9 genes encoding CRISPR-associated proteins have been found in the genome of Mycobacterium tuberculosis. The CRISPR-associated Cas2 is an endoribonuclease required for the acquisition of new spacers. In this study, Cas2 encoded by Rv2816c was expressed in Mycobacterium smegmatis lacking CRISPR-Cas system and its role in stress responses of M. smegmatis in vitro and within macrophages was studied. We found that Cas2 mediated M. smegmatis stress response changes were associated with the altered expression of sigma factors which involved in mycobacterial stress response and virulence. We also found that Cas2 decreased the survival of M. smegmatis within macrophages. This study provides new insights on the role of Cas2. PMID:26498723

  8. PK-PD modeling of individual lesion FDG-PET response to predict overall survival in patients with sunitinib-treated gastrointestinal stromal tumor.

    PubMed

    Schindler, E; Amantea, M A; Karlsson, M O; Friberg, L E

    2016-04-01

    Pharmacometric models were developed to characterize the relationships between lesion-level tumor metabolic activity, as assessed by the maximum standardized uptake value (SUVmax) obtained on [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), tumor size, and overall survival (OS) in 66 patients with gastrointestinal stromal tumor (GIST) treated with intermittent sunitinib. An indirect response model in which sunitinib stimulates tumor loss best described the typically rapid decrease in SUVmax during on-treatment periods and the recovery during off-treatment periods. Substantial interindividual and interlesion variability were identified in SUVmax baseline and drug sensitivity. A parametric time-to-event model identified the relative change in SUVmax at one week for the lesion with the most pronounced response as a better predictor of OS than tumor size. Based on the proposed modeling framework, early changes in FDG-PET response may serve as predictor for long-term outcome in sunitinib-treated GIST. PMID:27299707

  9. Bioclimatic Thresholds, Thermal Constants and Survival of Mealybug, Phenacoccus solenopsis (Hemiptera: Pseudococcidae) in Response to Constant Temperatures on Hibiscus

    PubMed Central

    Sreedevi, Gudapati; Prasad, Yenumula Gerard; Prabhakar, Mathyam; Rao, Gubbala Ramachandra; Vennila, Sengottaiyan; Venkateswarlu, Bandi

    2013-01-01

    Temperature-driven development and survival rates of the mealybug, Phenacoccussolenopsis Tinsley (Hemiptera: Pseudococcidae) were examined at nine constant temperatures (15, 20, 25, 27, 30, 32, 35 and 40°C) on hibiscus (Hibiscusrosa-sinensis L.). Crawlers successfully completed development to adult stage between 15 and 35°C, although their survival was affected at low temperatures. Two linear and four nonlinear models were fitted to describe developmental rates of P. solenopsis as a function of temperature, and for estimating thermal constants and bioclimatic thresholds (lower, optimum and upper temperature thresholds for development: Tmin, Topt and Tmax, respectively). Estimated thresholds between the two linear models were statistically similar. Ikemoto and Takai’s linear model permitted testing the equivalence of lower developmental thresholds for life stages of P. solenopsis reared on two hosts, hibiscus and cotton. Thermal constants required for completion of cumulative development of female and male nymphs and for the whole generation were significantly lower on hibiscus (222.2, 237.0, 308.6 degree-days, respectively) compared to cotton. Three nonlinear models performed better in describing the developmental rate for immature instars and cumulative life stages of female and male and for generation based on goodness-of-fit criteria. The simplified β type distribution function estimated Topt values closer to the observed maximum rates. Thermodynamic SSI model indicated no significant differences in the intrinsic optimum temperature estimates for different geographical populations of P. solenopsis. The estimated bioclimatic thresholds and the observed survival rates of P. solenopsis indicate the species to be high-temperature adaptive, and explained the field abundance of P. solenopsis on its host plants. PMID:24086597

  10. Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101.

    PubMed

    Costa Neves, Mafalda; Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​. PMID:26870619

  11. Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.

    PubMed

    Wang, Qin; Shi, Bi-Min; Xie, Fang; Fu, Zhao-Yang; Chen, Yong-Jing; An, Jing-Nan; Ma, Yu; Liu, Cui-Ping; Zhang, Xue-Kun; Zhang, Xue-Guang

    2016-07-15

    OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4(+) T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4(+) T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4(+) T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs. Confocal microscopy and coimmunoprecipitation analysis further revealed that OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of GD. PMID:27107937

  12. CD28 Promotes Plasma Cell Survival, Sustained Antibody Responses, and BLIMP-1 Upregulation through Its Distal PYAP Proline Motif

    PubMed Central

    Rozanski, Cheryl H.; Utley, Adam; Carlson, Louise M.; Farren, Matthew R.; Murray, Megan; Russell, Lisa M.; Nair, Jayakumar R.; Yang, ZhengYu; Brady, William; Garrett-Sinha, Lee Ann; Schoenberger, Stephen P.; Green, Jonathan M.; Boise, Lawrence H.

    2015-01-01

    In health, long-lived plasma cells (LLPC) are essential for durable protective humoral immunity, and, conversely, in disease are a major source of pathogenic Abs in autoimmunity, graft rejection, and allergy. However, the molecular basis for their longevity is largely unknown. We have recently found that CD28 signaling in plasma cells (PC) is essential for sustaining Ab titers, by supporting the survival of LLPC, but not short-lived PC (SLPC). We now find that, unlike SLPC, CD28 activation in LLPC induces prosurvival downstream Vav signaling. Knockin mice with CD28 cytoplasmic tail mutations that abrogate Vav signaling (CD28-AYAA) had significantly fewer LLPC but unaffected SLPC numbers, whereas mice with mutations that abrogate PI3K signaling (CD28-Y170F) were indistinguishable from wild-type controls. This was consistent with the loss of CD28’s prosurvival effect in LLPC from CD28-AYAA, but not CD28-Y170F, mice. Furthermore, the CD28 Vav motif in the B lineage was essential for the long-term maintenance of Ag-specific LLPC populations and Ab titers in vivo. Signaling downstream of the CD28 Vav motif induced previously undescribed transcriptional regulation of B lymphocyte–induced maturation protein-1, a key mediator of PC differentiation and maintenance. These findings suggest CD28 signaling in LLPC modulates the central B lymphocyte–induced maturation protein-1 transcriptional nexus involved in long-term survival and function. PMID:25833397

  13. Loss of Prohibitin Induces Mitochondrial Damages Altering β-Cell Function and Survival and Is Responsible for Gradual Diabetes Development

    PubMed Central

    Supale, Sachin; Thorel, Fabrizio; Merkwirth, Carsten; Gjinovci, Asllan; Herrera, Pedro L.; Scorrano, Luca; Meda, Paolo; Langer, Thomas; Maechler, Pierre

    2013-01-01

    Prohibitins are highly conserved proteins mainly implicated in the maintenance of mitochondrial function and architecture. Their dysfunctions are associated with aging, cancer, obesity, and inflammation. However, their possible role in pancreatic β-cells remains unknown. The current study documents the expression of prohibitins in human and rodent islets and their key role for β-cell function and survival. Ablation of Phb2 in mouse β-cells sequentially resulted in impairment of mitochondrial function and insulin secretion, loss of β-cells, progressive alteration of glucose homeostasis, and, ultimately, severe diabetes. Remarkably, these events progressed over a 3-week period of time after weaning. Defective insulin supply in β-Phb2−/− mice was contributed by both β-cell dysfunction and apoptosis, temporarily compensated by increased β-cell proliferation. At the molecular level, we observed that deletion of Phb2 caused mitochondrial abnormalities, including reduction of mitochondrial DNA copy number and respiratory chain complex IV levels, altered mitochondrial activity, cleavage of L-optic atrophy 1, and mitochondrial fragmentation. Overall, our data demonstrate that Phb2 is essential for metabolic activation of mitochondria and, as a consequence, for function and survival of β-cells. PMID:23863811

  14. Survival, growth, detoxifying and antioxidative responses of earthworms (Eisenia fetida) exposed to soils with industrial DDT contamination.

    PubMed

    Shi, Yajuan; Zhang, Qiangbin; Huang, Dunqi; Zheng, Xiaoqi; Shi, Yajing

    2016-03-01

    The survival, growth, activity of the biotransformation system phase II enzyme glutathione-S-transferase (GST) and the oxidative defense enzyme catalase (CAT) of earthworms exposed to the contaminated soils from a former DDT plant and reference soils were investigated, and compared with the corresponding indicators in simulated soil-earthworm system, unpolluted natural soils with spiked-in DDT series, to identify the toxic effects of DDT on earthworms and their cellular defense system in complex soil system. The results indicated that DDT level in the contaminated soils was significantly higher than that in the reference soils with similar level of other pollutants and soil characters. The mortality, growth inhibition rates, GST and CST activities of earthworms exposed to the contaminated soils were significantly higher than that in reference soils. The contribution of historical DDT in contaminated soils to earthworms was confirmed by the DDT spiked tests. DDT spiked in soils at rates of higher than 200 mg·kg(-1) was significantly toxic to both the survival and the growth of earthworms. DDT significantly stimulated GST and CAT activity in earthworms after 14 days. The CAT and GST activities were also stimulated by DDT exposure at rates of 100 mg·kg(-1) after chronic exposure (42 days). The results provide implications for validating the extrapolation from laboratory simulated soils criteria to contaminated soils and for making site risk assessments. PMID:26969436

  15. The Effects of TiO2 Nanodot Films with RGD Immobilization on Light-Induced Cell Sheet Technology

    PubMed Central

    Yu, Meng-Liu; Yu, Meng-Fei; Zhu, Li-Qin; Wang, Tian-Tian; Zhou, Yi; Wang, Hui-Ming

    2015-01-01

    Cell sheet technology is a new strategy in tissue engineering which could be possible to implant into the body without a scaffold. In order to get an integrated cell sheet, a light-induced method via UV365 is used for cell sheet detachment from culture dishes. In this study, we investigated the possibility of cell detachment and growth efficiency on TiO2 nanodot films with RGD immobilization on light-induced cell sheet technology. Mouse calvaria-derived, preosteoblastic (MC3T3-E1) cells were cultured on TiO2 nanodot films with (TR) or without (TN) RGD immobilization. After cells were cultured with or without 5.5 mW/cm2 UV365 illumination, cell morphology, cell viability, osteogenesis related RNA and protein expression, and cell detachment ability were compared, respectively. Light-induced cell detachment was possible when cells were cultured on TR samples. Also, cells cultured on TR samples showed better cell viability, alongside higher protein and RNA expression than on TN samples. This study provides a new biomaterial for light-induced cell/cell sheet harvesting. PMID:26417596

  16. LIGHT SCATTERING: Observation of multiple scattering of laser radiation from a light-induced jet of microparticles in suspension

    NASA Astrophysics Data System (ADS)

    Kondrat'ev, Andrei V.

    2004-06-01

    Variation in the correlation function of light multiply scattered by a random medium was observed with increasing the incident beam power. The light-induced motion of microparticles in suspension, caused by a high-power laser radiation, serves as an additional factor in the decorrelation of the scattered light. The experimental data are in good agreement with the results of theoretical analysis.

  17. Correlating in Vitro and in Vivo Activities of Light-Inducible Dimers: A Cellular Optogenetics Guide.

    PubMed

    Hallett, Ryan A; Zimmerman, Seth P; Yumerefendi, Hayretin; Bear, James E; Kuhlman, Brian

    2016-01-15

    Light-inducible dimers are powerful tools for cellular optogenetics, as they can be used to control the localization and activity of proteins with high spatial and temporal resolution. Despite the generality of the approach, application of light-inducible dimers is not always straightforward, as it is frequently necessary to test alternative dimer systems and fusion strategies before the desired biological activity is achieved. This process is further hindered by an incomplete understanding of the biophysical/biochemical mechanisms by which available dimers behave and how this correlates to in vivo function. To better inform the engineering process, we examined the biophysical and biochemical properties of three blue-light-inducible dimer variants (cryptochrome2 (CRY2)/CIB1, iLID/SspB, and LOVpep/ePDZb) and correlated these characteristics to in vivo colocalization and functional assays. We find that the switches vary dramatically in their dark and lit state binding affinities and that these affinities correlate with activity changes in a variety of in vivo assays, including transcription control, intracellular localization studies, and control of GTPase signaling. Additionally, for CRY2, we observe that light-induced changes in homo-oligomerization can have significant effects on activity that are sensitive to alternative fusion strategies. PMID:26474029

  18. Electro-optic phase modulation in light induced self-written waveguides propagated in a 5CB doped photopolymer.

    PubMed

    Jemal, Abdelmonem; Ben Belgacem, Mohamed; Kamoun, Saber; Gargouri, Mohamed; Honorat Dorkenoo, Kokou D; Barsella, Alberto; Mager, Loïc

    2013-01-28

    We present the inscription of a Light Induced Self-Written (LISW) waveguide in a 4-cyano-4'-pentylbipheny (5CB) doped photopolymer. The dynamic reorientation of the 5CB molecules in the material under applied electric field leads to birefringence in LISW waveguide and thus allows the control of the phase of the guided mode. PMID:23389136

  19. Visible Light-Induced Radical Rearrangement to Construct C-C Bonds via an Intramolecular Aryl Migration/Desulfonylation Process.

    PubMed

    Li, Yuyuan; Hu, Bei; Dong, Wuheng; Xie, Xiaomin; Wan, Jun; Zhang, Zhaoguo

    2016-08-19

    A highly efficient intramolecular selective aryl migration/desulfonylation of 2-bromo-N-aryl-N-(arenesulfonyl)amide via visible light-induced photoredox catalysis has been accomplished. This approach allows for the construction of a variety of multisubstituted N,2-diarylacetamide under mild reaction conditions. PMID:27351977

  20. Difunctionalization of Alkenes via the Visible-Light-Induced Trifluoromethylarylation/1,4-Aryl Shift/Desulfonylation Cascade Reactions.

    PubMed

    Zheng, Lewei; Yang, Chao; Xu, ZhaoZhong; Gao, Fei; Xia, Wujiong

    2015-06-01

    A novel visible-light-induced trifluoromethylarylation/1,4-aryl shift/desulfonylation cascade reaction using CF3SO2Cl as CF3 source was described. The protocol provides an efficient approach for the synthesis of α-aryl-β-trifluoromethyl amides and/or CF3-containing oxindoles as well as the isoquinolinediones under benign conditions. PMID:25955879

  1. Additive effect of mPer1 and mPer2 antisense oligonucleotides on light-induced phase shift.

    PubMed

    Wakamatsu, H; Takahashi, S; Moriya, T; Inouye, S T; Okamura, H; Akiyama, M; Shibata, S

    2001-01-22

    It is well known that light induces both mPer1 and mPer2 mRNA in the suprachiasmatic nucleus. We have reported that mPer1 antisense oligonucleotides (ODNs) inhibited the light-induced phase delays of mouse locomotor rhythm. In this study, we asked whether both or either mPer1 or mPer2 expression is necessary to induce the phase shift. We examined the effects of inhibition of mRNA expression on light-induced phase delays of mouse circadian behavior rhythm. Light-induced phase delays were moderately attenuated by microinjection of mPer1 or mPer2 antisense ODN, but not by mPer3 antisense or mPer1, mPer2 scrambled ODNs, whereas following simultaneous injection of both mPer1 and mPer2 antisense ODNs they disappeared. The present results suggest that acute induction of mPer1 and mPer2 gene play an additive effect on photic entrainment. PMID:11201072

  2. Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy

    PubMed Central

    Tullis, Brandon E.; Ryals, Renee C.; Coyner, Aaron S.; Gale, Michael J.; Nicholson, Alex,; Ku, Cristy,; Regis, Dain,; Sinha, Wrik,; Datta, Shreya,; Wen, Yuquan,; Yang, Paul,; Pennesi, Mark E.

    2015-01-01

    Purpose To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is protective against light-induced retinopathy in BALB/c mice. Methods BALB/c mice were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24, and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48 hours after exposure. Additionally, a single injection regimen was evaluated by injecting mice with 50 mg/kg sarpogrelate once immediately prior to light exposure. To investigate the potential for additive effects of serotonin receptor agents, a combination therapy consisting of sarpogrelate (15 mg/kg) and 8-OH-DPAT (1 mg/kg) was evaluated with the 5-day treatment regimen. Neuroprotection was characterized by the preservation of retinal thickness and function, measured by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), respectively. Results Mice that were light damaged and injected with saline had significantly reduced outer retinal thickness, total retinal thickness, and ERG amplitudes compared with naïve mice. A 5-day administration of 15, 30, or 40 mg/kg of sarpogrelate was able to partially protect retinal morphology and full protection of retinal morphology was achieved with a 50 mg/kg dose. Both 15 and 30 mg/kg doses of sarpogrelate partially preserved retinal function measured by ERG, whereas 40 and 50 mg/kg doses fully preserved retinal function. Additionally, a single administration of 50 mg/kg sarpogrelate was able to fully preserve both retinal morphology and function. Administration of 15 mg/kg of sarpogrelate and 1 mg/kg of 8-OH-DPAT together demonstrated an additive effect and fully preserved retinal morphology. Conclusions A 5- or 1-day treatment with 50 mg/kg sarpogrelate can completely protect the retina of BALB/c mice from light-induced retinopathy. Partial protection can be achieved with lower doses starting at 15 mg/kg and protection increases in a dose-dependent manner. Treatment with low

  3. TD-DFT study of the light-induced spin crossover of Fe(III) complexes.

    PubMed

    Saureu, Sergi; de Graaf, Coen

    2016-01-14

    Two light-induced spin-crossover Fe(III) compounds have been studied with time-dependent density functional theory (TD-DFT) to investigate the deactivation mechanism and the role of the ligand-field states as intermediates in this process. The B3LYP* functional has previously shown its ability to accurately describe (light-induced) spin-crossover in Fe(II) complexes. Here, we establish its performance for Fe(III) systems using [Fe(qsal)2](+) (Hqsal = 2-[(8-quinolinylimino)methyl]phenol) and [Fe(pap)2](+) (Hpap = 2-(2-pyridylmethyleneamino)phenol) as test cases comparing the B3LYP* results to experimental information and to multiconfigurational wave function results. In addition to rather accurate high spin (HS) and low spin (LS) state geometries, B3LYP* also predicts ligand-to-metal charge transfer (LMCT) states with large oscillator strength in the energy range where the UV-VIS spectrum shows an intense absorption band, whereas optically allowed π-π* excitations on the ligands were calculated at higher energy. Subsequently, we have generated a two-dimensional potential energy surface of the HS and LS states varying the Fe-N and Fe-O distances. LMCT and metal centered (MC) excited states were followed along the approximate minimal energy path that connects the minima of the HS and LS on this surface. The (2)LMCT state has a minimum in the same region as the initial LS state, where we also observe a crossing with the intermediate spin (IS) state. Upon the expansion of the coordination sphere of the Fe(III) ion, the IS state crosses with the HS state and further expansion of the coordination sphere leads to the excited spin state trapping as observed in experiment. The calculation of the intersystem crossing rates reveals that the deactivation from (2)LMCT → IS → HS competes with the (2)LMCT → IS → LS pathway, in line with the low efficiency encountered in experiments. PMID:26660866

  4. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  5. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

    PubMed Central

    Fischer, E; Marano, M A; Van Zee, K J; Rock, C S; Hawes, A S; Thompson, W A; DeForge, L; Kenney, J S; Remick, D G; Bloedow, D C

    1992-01-01

    The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock. Young, healthy baboons received either a sublethal dose of lipopolysaccharide (LPS) or an LD100 of live Escherichia coli bacteria, and one half of the animals in each group were continuously infused with IL-1 receptor antagonist (IL-1ra). Plasma IL-1 beta was not detected in this model of endotoxemia. Administration of IL-1ra had only minimal effects on the modest hemodynamic and metabolic responses to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In contrast, high circulating levels of IL-1 beta (range 300-800 pg/ml) were seen during lethal E. coli septic shock. IL-1ra treatment significantly attenuated the decrease in mean arterial blood pressure (MAP) (from -72 +/- 8 to -43 +/- 6 mm Hg; P less than 0.05) and cardiac output (from -0.81 +/- 0.17 to -0.48 +/- 0.15 liter/min; P less than 0.05), and significantly improved survival from 43 to 100% at 24 h (P less than 0.05). The plasma IL-1 beta and IL-6 responses to lethal E. coli septic shock were also significantly diminished by IL-1ra treatment (P less than 0.05), whereas tumor necrosis factor-alpha (TNF alpha) concentrations were unaffected. We conclude that an exaggerated systemic IL-1 beta response is characteristic of lethal E. coli septic shock, and contributes significantly to the hemodynamic and metabolic consequences of E. coli septic shock. IL-1ra can significantly attenuate the cytokine cascade and improve survival. PMID:1533231

  6. The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light

    PubMed Central

    Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D.; Eisenberg, Eli; Foulkes, Nicholas S.; Gothilf, Yoav

    2014-01-01

    Light constitutes a primary signal whereby endogenous circadian clocks are synchronized (‘entrained’) with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3′UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

  7. The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light.

    PubMed

    Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D; Eisenberg, Eli; Foulkes, Nicholas S; Gothilf, Yoav

    2014-04-01

    Light constitutes a primary signal whereby endogenous circadian clocks are synchronized ('entrained') with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3'UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

  8. Surviving but not thriving: inconsistent responses of zooxanthellate jellyfish polyps to ocean warming and future UV-B scenarios.

    PubMed

    Klein, Shannon G; Pitt, Kylie A; Carroll, Anthony R

    2016-01-01

    Complex changes to UV radiation at the Earth's surface are occurring concurrently with ocean warming. Despite few empirical tests, jellyfish are hypothesised to be increasing in some parts of the world because they are robust to environmental stressors. Here we examine the effects of UV-B and ocean warming projections on zooxanthellate jellyfish polyps. We exposed Cassiopea sp. polyps to three levels of UV-B (future-low (1.43 Wm(2)), current (1.60 Wm(2)), future-high (1.77 Wm(2))) and two levels of temperature (current-day (25 °C) and future (28 °C)) over 6 weeks. The intensity of UV-B was varied throughout the day to mimic diel variation in UV-B irradiance. Polyp survival, asexual reproduction and YII were measured. In the current and future-high UV-B treatments, more polyps were produced in 25 °C than 28 °C. This pattern, however, was reversed under future-low UV-B conditions, where more polyps were produced at 28 °C. YII was highest under current summer conditions and future conditions of low UV-B and increased temperature. YII, however, was reduced under high UV-B conditions but was further reduced with warming. Our results suggest that although Cassiopea polyps may survive elevated UV-B and warming conditions, they are unlikely to thrive. If, however, UV-B radiation decreases then ocean warming may facilitate increases in Cassiopea populations. PMID:27374028

  9. Surviving but not thriving: inconsistent responses of zooxanthellate jellyfish polyps to ocean warming and future UV-B scenarios

    NASA Astrophysics Data System (ADS)

    Klein, Shannon G.; Pitt, Kylie A.; Carroll, Anthony R.

    2016-07-01

    Complex changes to UV radiation at the Earth’s surface are occurring concurrently with ocean warming. Despite few empirical tests, jellyfish are hypothesised to be increasing in some parts of the world because they are robust to environmental stressors. Here we examine the effects of UV-B and ocean warming projections on zooxanthellate jellyfish polyps. We exposed Cassiopea sp. polyps to three levels of UV-B (future-low (1.43 Wm2), current (1.60 Wm2), future-high (1.77 Wm2)) and two levels of temperature (current-day (25 °C) and future (28 °C)) over 6 weeks. The intensity of UV-B was varied throughout the day to mimic diel variation in UV-B irradiance. Polyp survival, asexual reproduction and YII were measured. In the current and future-high UV-B treatments, more polyps were produced in 25 °C than 28 °C. This pattern, however, was reversed under future-low UV-B conditions, where more polyps were produced at 28 °C. YII was highest under current summer conditions and future conditions of low UV-B and increased temperature. YII, however, was reduced under high UV-B conditions but was further reduced with warming. Our results suggest that although Cassiopea polyps may survive elevated UV-B and warming conditions, they are unlikely to thrive. If, however, UV-B radiation decreases then ocean warming may facilitate increases in Cassiopea populations.

  10. Surviving but not thriving: inconsistent responses of zooxanthellate jellyfish polyps to ocean warming and future UV-B scenarios

    PubMed Central

    Klein, Shannon G.; Pitt, Kylie A.; Carroll, Anthony R.

    2016-01-01

    Complex changes to UV radiation at the Earth’s surface are occurring concurrently with ocean warming. Despite few empirical tests, jellyfish are hypothesised to be increasing in some parts of the world because they are robust to environmental stressors. Here we examine the effects of UV-B and ocean warming projections on zooxanthellate jellyfish polyps. We exposed Cassiopea sp. polyps to three levels of UV-B (future-low (1.43 Wm2), current (1.60 Wm2), future-high (1.77 Wm2)) and two levels of temperature (current-day (25 °C) and future (28 °C)) over 6 weeks. The intensity of UV-B was varied throughout the day to mimic diel variation in UV-B irradiance. Polyp survival, asexual reproduction and YII were measured. In the current and future-high UV-B treatments, more polyps were produced in 25 °C than 28 °C. This pattern, however, was reversed under future-low UV-B conditions, where more polyps were produced at 28 °C. YII was highest under current summer conditions and future conditions of low UV-B and increased temperature. YII, however, was reduced under high UV-B conditions but was further reduced with warming. Our results suggest that although Cassiopea polyps may survive elevated UV-B and warming conditions, they are unlikely to thrive. If, however, UV-B radiation decreases then ocean warming may facilitate increases in Cassiopea populations. PMID:27374028

  11. Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias

    PubMed Central

    Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

    2016-01-01

    Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias – decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis. DOI: http://dx.doi.org/10.7554/eLife.14175.001 PMID:27240733

  12. Light induced suppression of sulfur in a cesium sputter ion source.

    PubMed

    Martschini, Martin; Rohlén, Johan; Andersson, Pontus; Golser, Robin; Hanstorp, Dag; Lindahl, Anton O; Priller, Alfred; Steier, Peter; Forstner, Oliver

    2012-04-01

    New techniques for suppression of atomic isobars in negative ion beams are of great interest for accelerator mass spectrometry (AMS). Especially small and medium-sized facilities can significantly extend their measurement capabilities to new interesting isotopes with a technique independent of terminal voltage. In a new approach, the effect of continuous wave laser light directed towards the cathode surface in a cesium sputter ion source of the Middleton type was studied. The laser light induced a significant change in oxygen, sulfur and chlorine negative ion production from a AgCl target. Approximately 100 mW of laser light reduced the sulfur to chlorine ratio by one order of magnitude. The effect was found to depend on laser power and ion source parameters but not on the laser wavelength. The time constant of the effect varied from a few seconds up to several minutes. Experiments were first performed at the ion beam facility GUNILLA at University of Gothenburg with macroscopic amounts of sulfur. The results were then reproduced at the VERA AMS facility with chemically cleaned AgCl targets containing ∼1 ppm sulfur. The physical explanation behind the effect is still unclear. Nevertheless, the technique has been successfully applied during a regular AMS measurement of (36)Cl. PMID:23576897

  13. Iterative experiment design guides the characterization of a light-inducible gene expression circuit

    PubMed Central

    Ruess, Jakob; Parise, Francesca; Milias-Argeitis, Andreas; Khammash, Mustafa; Lygeros, John

    2015-01-01

    Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time. PMID:26085136

  14. Modeling light-induced currents in the eye of Chlamydomonas reinhardtii.

    PubMed

    Gradmann, D; Ehlenbeck, S; Hegemann, P

    2002-09-15

    Rhodopsin-mediated electrical events in green algae have been recorded in the past from the eyes of numerous micro-algae like Haematococcus pluvialis, Chlamydomonas reinhardtii and Volvox carteri. However, the electrical data gathered by suction-pipette techniques could be interpreted in qualitative terms only. Here we present two models that allow a quantitative analysis of such results: First, an electrical analog circuit for the cell in suction pipette configuration is established. Applying this model to experimental data from unilluminated cells of C. reinhardtii yields a membrane conductance of about 3 Sm(-2). Furthermore, an analog circuit allows the determination of the photocurrent fraction that is recorded under experimental conditions. Second, a reaction scheme of a rhodopsin-type photocycle with an early Ca(2+) conductance and a later H(+) conductance is presented. The combination of both models provides good fits to light-induced currents recorded from C. reinhardtii. Finally, it allowed the calculation of the impact of each model parameter on the time courses of observable photocurrent and of inferred transmembrane voltage. The reduction of the flash-to-peak times at increasing light intensities are explained by superposition of two kinetically distinct rhodopsins and by assuming that the Ca(2+)-conducting state decays faster at more positive membrane voltages. PMID:12235485

  15. Light induced controlled release of fragrances by Norrish type II photofragmentation of alkyl phenyl ketones.

    PubMed

    Levrand, Barbara; Herrmann, Andreas

    2002-11-01

    The use of alkyl phenyl ketones as delivery systems for the controlled release of fragrances was investigated by photoirradiation of undegassed solutions with a xenon lamp as well as natural sunlight. A large variety of precursor compounds was prepared efficiently in a few reaction steps from commercially available starting materials. The Norrish type II photofragmentation was found to be the predominant reaction pathway to yield the desired perfumery alkenes and acetophenones in polar and apolar solution. Systematic GC-MS analysis of the irradiated solutions allowed identification of a series of side products that are due to the presence of oxygen. A detailed analysis of the product distribution after irradiation was carried out for a series of 4-alkoxy-1-phenylbutanone derivatives. Besides the expected acetophenones, vinyl ethers and phenylcyclobutanols, the formation of alkyl formates, alcohols and 4-oxo-4-phenylbutanoates was observed. The product distribution as influenced by solvent polarity, precursor concentration and substituent effects was investigated. The utility of alkyl phenyl ketones as precursors for the light induced controlled release of fragrances under natural daylight conditions was also demonstrated. PMID:12659532

  16. Biomimetic Water-Collecting Fabric with Light-Induced Superhydrophilic Bumps.

    PubMed

    Wang, Yuanfeng; Wang, Xiaowen; Lai, Chuilin; Hu, Huawen; Kong, Yeeyee; Fei, Bin; Xin, John H

    2016-02-10

    To develop an efficient water-collecting surface that integrates both fast water-capturing and easy drainage properties is of high current interest for addressing global water issues. In this work, a superhydrophobic surface was fabricated on cotton fabric via manipulation of both the surface roughness and surface energy. This was followed by a subsequent spray coating of TiO2 nanosol that created light-induced superhydrophilic bumps with a unique raised structure as a result of the interfacial tension of the TiO2 nanosol sprayed on the superhydrophobic fiber surface. These raised TiO2 bumps induce both a wettability gradient and a shape gradient, synergistically accelerating water coalescence and water collection. The in-depth study revealed that the quantity and the distribution of the TiO2 had a significant impact on the final water collection efficiency. This inexpensive and facilely fabricated fabric biomimicks the desert beetle's back and spider silk, which are capable of fog harvesting without additional energy consumption. PMID:26652924

  17. Ultraviolet light-induced atom desorption for large rubidium and potassium magneto-optical traps

    SciTech Connect

    Klempt, C.; Zoest, T. van; Henninger, T.; Topic, O.; Rasel, E.; Ertmer, W.; Arlt, J.

    2006-01-15

    We show that light-induced atom desorption (LIAD) can be used as a flexible atomic source for large {sup 87}Rb and {sup 40}K magneto-optical traps. The use of LIAD at short wavelengths allows for fast switching of the desired vapor pressure and permits experiments with long trapping and coherence times. The wavelength dependence of the LIAD effect for both species was explored in a range from 630 to 253 nm in an uncoated quartz cell and a stainless steel chamber. Only a few mW/cm{sup 2} of near-UV light produce partial pressures that are high enough to saturate a magneto-optical trap at 3.5x10{sup 9} {sup 87}Rb atoms or 7x10{sup 7} {sup 40}K atoms. Loading rates as high as 1.2x10{sup 9} {sup 87}Rb atoms/s and 8x10{sup 7} {sup 40}K atoms/s were achieved without the use of a secondary atom source. After the desorption light is turned off, the pressure quickly decays back to equilibrium with a time constant as short as 200 {mu}s, allowing for long trapping lifetimes after the MOT loading phase.

  18. Compartmentalization and Ca2+ buffering are essential for prevention of light induced retinal degeneration

    PubMed Central

    Weiss, Shirley; Kohn, Elkana; Dadon, Daniela; Katz, Ben; Peters, Maximilian; Lebendiker, Mario; Kosloff, Mickey; Jo Colley, Nansi; Minke, Baruch

    2012-01-01

    Fly photoreceptors are polarized cells, which have an extended interface between their cell body and the light signaling compartment, the rhabdomere. Upon intense illumination, rhabdomeric calcium concentration reaches millimolar levels that would be toxic if Ca2+ diffusion between the rhabdomere and cell body was not robustly attenuated. Yet, it is not clear how such effective attenuation is obtained. Here we show that Ca2+ homeostasis in the photoreceptor cell relies on the protein calphotin. This unique protein functions as an immobile Ca2+ buffer, which is localized along the base of the rhabdomere, separating the signaling compartment from the cell body. Generation and analyses of transgenic Drosophila strains, in which calphotin expression levels were reduced in a graded manner, showed that moderately reduced calphotin expression impaired Ca2+ homeostasis while calphotin elimination resulted in severe light dependent photoreceptor degeneration. Electron microscopy, electrophysiology and optical methods revealed that the degeneration was rescued by prevention of Ca2+ overload via overexpression of CalX, the Na+-Ca2+ exchanger. In addition, Ca2+ imaging experiments showed that reduced calphotin levels resulted in abnormally fast kinetics of Ca2+elevation in photoreceptor cells. Together, the data suggest that calphotin functions as a Ca2+ buffer; a possibility which we directly demonstrate by expressing calphotin in a heterologous expression system. We propose that calphotin-mediated compartmentalization and Ca2+ buffering constitute an effective strategy to protect cells from Ca2+ overload and light induced degeneration. PMID:23077055

  19. Light-induced atom desorption from glass surfaces characterized by X-ray photoelectron spectroscopy

    NASA Astrophysics Data System (ADS)

    Kumagai, Ryo; Hatakeyama, Atsushi

    2016-07-01

    We analyzed the surfaces of vitreous silica (quartz) and borosilicate glass (Pyrex) substrates exposed to rubidium (Rb) vapor by X-ray photoelectron spectroscopy (XPS) to understand the surface conditions of alkali metal vapor cells. XPS spectra indicated that Rb atoms adopted different bonding states in quartz and Pyrex. Furthermore, Rb atoms in quartz remained in the near-surface region, while they diffused into the bulk in Pyrex. For these characterized surfaces, we measured light-induced atom desorption (LIAD) of Rb atoms. Clear differences in time evolution, photon energy dependence, and substrate temperature dependence were found; the decay of LIAD by continuous ultraviolet irradiation for quartz was faster than that for Pyrex, a monotonic increase in LIAD with increasing photon energy from 1.8 to 4.3 eV was more prominent for quartz, and LIAD from quartz was more efficient at higher temperatures in the range from 300 to 580 K, while that from Pyrex was almost independent of temperature.

  20. Model for the light-induced magnetization in singly charged quantum dots

    NASA Astrophysics Data System (ADS)

    Henriques, A. B.; Cordeiro, R. C.; Koenraad, P. M.; Otten, F. W. M.; Bayer, M.

    2015-02-01

    Magnetization is induced in an ensemble of quantum dots, each charged with a single electron, when it is illuminated with a short circularly polarized light pulse that is resonant with the fundamental energy gap of the quantum dots. In this investigation, a quantum-mechanical model for the light-induced magnetization is presented. The phase of the magnetization precession as a function of the strength of the magnetic field in a Voigt geometry is in excellent agreement with experimental data measured on (In,Ga)As singly charged quantum dot ensembles. It is demonstrated that the precession of the hole in the trion plays a vital role because it determines the amplitude and phase of the magnetization precession. The model could also be easily extended to describe positively charged quantum dots. We also suggest that our theory, combined with measurements of the phase as a function of magnetic field, can be used as a technique to measure the resonant trion lifetime as a function of QD emission energy.

  1. Quantification of Canine Dental Plaque Using Quantitative Light-Induced Fluorescence.

    PubMed

    Wallis, Corrin; Gill, Yadvinder; Colyer, Alison; Davis, Ian; Allsopp, Judi; Komarov, Gleb; Higham, Susan; Harris, Stephen

    2016-03-01

    The aim of this work was to evaluate Quantitative Light-induced Fluorescence (QLF) as an alternative to the established Logan and Boyce method for determining plaque coverage of dogs' teeth. In a series of studies in conscious and anesthetized dogs, QLF showed good intra-photographer repeatability (coefficient of variation [CV] of 7.5% for undisclosed teeth) and inter-photographer reproducibility (CV of 3.2% for undisclosed teeth and 8.5% for disclosed teeth). The QLF software accurately identifies areas of plaque as demonstrated by comparison to the variability of 5 human scorers, manually marking plaque on QLF-acquired images (P = 0.1). There was good agreement with the modified Logan and Boyce method in the percentage reduction in plaque accumulation measured when dogs were fed an oral care chew versus no chew. To see a 15% difference in plaque accumulation, which is considered sufficient by the Veterinary Oral Health Council to differentiate between 2 treatments, a retrospective power analysis (90%) of the data established that only 7 dogs would be required, compared to 19 dogs for the modified Logan and Boyce method. QLF is a reliable method for measuring dental plaque in dogs with the added advantage that it is not subjective and requires fewer animals. PMID:27487653

  2. Light-induced negative differential resistance in graphene/Si-quantum-dot tunneling diodes.

    PubMed

    Lee, Kyeong Won; Jang, Chan Wook; Shin, Dong Hee; Kim, Jong Min; Kang, Soo Seok; Lee, Dae Hun; Kim, Sung; Choi, Suk-Ho; Hwang, Euyheon

    2016-01-01

    One of the interesing tunneling phenomena is negative differential resistance (NDR), the basic principle of resonant-tunneling diodes. NDR has been utilized in various semiconductor devices such as frequency multipliers, oscillators, relfection amplifiers, logic switches, and memories. The NDR in graphene has been also reported theoretically as well as experimentally, but should be further studied to fully understand its mechanism, useful for practical device applications. Especially, there has been no observation about light-induced NDR (LNDR) in graphene-related structures despite very few reports on the LNDR in GaAs-based heterostructures. Here, we report first observation of LNDR in graphene/Si quantum dots-embedded SiO2 (SQDs:SiO2) multilayers (MLs) tunneling diodes. The LNDR strongly depends on temperature (T) as well as on SQD size, and the T dependence is consistent with photocurrent (PC)-decay behaviors. With increasing light power, the PC-voltage curves are more structured with peak-to-valley ratios over 2 at room temperature. The physical mechanism of the LNDR, governed by resonant tunneling of charge carriers through the minibands formed across the graphene/SQDs:SiO2 MLs and by their nonresonant phonon-assisted tunneling, is discussed based on theoretical considerations. PMID:27465107

  3. Analysis of Light-Induced Transmembrane Ion Gradients and Membrane Potential in Photosystem I Proteoliposomes

    SciTech Connect

    Pennisi, Cristian P.; Greenbaum, Elias; Yoshida, Ken

    2010-01-01

    Photosystem I (PSI) complexes can support a light-driven electrochemical gradient for protons, which is the driving force for energy-conserving reactions across biological membranes. In this work, a computational model that enables a quantitative description of the light-induced proton gradients across the membrane of PSI proteoliposomes is presented. Using a set of electrodiffusion equations, a compartmental model of a vesicle suspended in aqueous medium was studied. The light-mediated proton movement was modeled as a single proton pumping step with backpressure of the electric potential. The model fits determinations of pH obtained from PSI proteoliposomes illuminated in the presence of mediators of cyclic electron transport. The model also allows analysis of the proton gradients in relation to the transmembrane ion fluxes and electric potential. Sensitivity analysis enabled a determination of the parameters that have greater influence on steady-state levels and onset/decay rates of transmembrane pH and electric potential. This model could be used as a tool for optimizing PSI proteoliposomes for photo-electrochemical applications.

  4. Cyanobacterial high-light-inducible proteins--Protectors of chlorophyll-protein synthesis and assembly.

    PubMed

    Komenda, Josef; Sobotka, Roman

    2016-03-01

    Cyanobacteria contain a family of genes encoding one-helix high-light-inducible proteins (Hlips) that are homologous to light harvesting chlorophyll a/b-binding proteins of plants and algae. Based on various experimental approaches used for their study, a spectrum of functions that includes regulation of chlorophyll biosynthesis, transient chlorophyll binding, quenching of singlet oxygen and non-photochemical quenching of absorbed energy is ascribed to Hlips. However, these functions had not been supported by conclusive experimental evidence until recently when it became clear that Hlips are able to quench absorbed light energy and assist during terminal step(s) of the chlorophyll biosynthesis and early stages of Photosystem II assembly. In this review we summarize and discuss the present knowledge about Hlips and provide a model of how individual members of the Hlip family operate during the biogenesis of chlorophyll-proteins, namely Photosystem II. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. PMID:26341017

  5. Use of quantitative light-induced fluorescence to monitor tooth whitening

    NASA Astrophysics Data System (ADS)

    Amaechi, Bennett T.; Higham, Susan M.

    2001-04-01

    The changing of tooth shade by whitening agents occurs gradually. Apart from being subjective and affected by the conditions of the surroundings, visual observation cannot detect a very slight change in tooth color. An electronic method, which can communicate the color change quantitatively, would be more reliable. Quantitative Light- induced Fluorescence (QLF) was developed to detect and assess dental caries based on the phenomenon of change of autofluorescence of a tooth by demineralization. However, stains on the tooth surface exhibit the same phenomenon, and therefore QLF can be used to measure the percentage fluorescence change of stained enamel with respect to surrounding unstained enamel. The present study described a technique of assessing the effect of a tooth-whitening agent using QLF. This was demonstrated in two experiments in which either wholly or partially stained teeth were whitened by intermittent immersion in sodium hypochlorite. Following each immersion, the integrated fluorescence change due to the stain was quantified using QLF. In either situation, the value of (Delta) Q decreased linearly as the tooth regained its natural shade. It was concluded that gradual changing of the shade of discolored teeth by a whitening agent could be quantified using QLF.

  6. Quantified light-induced fluorescence, review of a diagnostic tool in prevention of oral disease

    NASA Astrophysics Data System (ADS)

    de Josselin de Jong, Elbert; Higham, Susan M.; Smith, Philip W.; van Daelen, Catherina J.; van der Veen, Monique H.

    2009-05-01

    Diagnostic methods for the use in preventive dentistry are being developed continuously. Few of these find their way into general practice. Although the general trend in medicine is to focus on disease prevention and early diagnostics, in dentistry this is still not the case. Nevertheless, in dental research some of these methods seem to be promising for near future use by the general dental professional. In this paper an overview is given of a method called quantitative light-induced fluorescence or (QLF) in which visible and harmless light excites the teeth in the patient's mouth to produce fluorescent images, which can be stored on disk and computer analyzed. White spots (early dental caries) are detected and quantified as well as bacterial metabolites on and in the teeth. An overview of research to validate the technique and modeling to further the understanding of the technique by Monte Carlo simulation is given and it is shown that the fluorescence phenomena can be described by the simulation model in a qualitative way. A model describing the visibility of red fluorescence from within the dental tissue is added, as this was still lacking in current literature. An overview is given of the clinical images made with the system and of the extensive research which has been done. The QLF™ technology has been shown to be of importance when used in clinical trials with respect to the testing of toothpastes and preventive treatments. It is expected that the QLF™ technology will soon find its way into the general dental practice.

  7. Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer

    NASA Astrophysics Data System (ADS)

    Nishiyama, Nobuhiro; Iriyama, Aya; Jang, Woo-Dong; Miyata, Kanjiro; Itaka, Keiji; Inoue, Yuji; Takahashi, Hidenori; Yanagi, Yasuo; Tamaki, Yasuhiro; Koyama, Hiroyuki; Kataoka, Kazunori

    2005-12-01

    The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.

  8. A new photoacoustic method based on the modulation of the light induced absorption coefficient

    NASA Astrophysics Data System (ADS)

    Engel, S.; Wenisch, C.; Müller, F. A.; Gräf, S.

    2016-04-01

    The present study reports on a new photoacoustic (PA) measurement method that is suitable for the investigation of light induced absorption effects including e.g. excited state absorption. Contrary to the modulation of the radiation intensity used in conventional PA-methods, the key principle of this novel setup is based on the modulation of the induced absorption coefficient by light. For this purpose, a pump-probe setup with a pulsed pump laser beam and a continuous probe laser beam is utilized. In this regime, the potential influence of heat on the PA-signal is much smaller when compared to arrangements with pulsed probe beam and continuous pump beam. Beyond that, the negative effect of thermal lenses can be neglected. Thus, the measurement technique is well-suited for materials exhibiting a strong absorption at the pump wavelength. The quantitative analysis of the induced absorption coefficient was achieved by the calibration of the additional PA-signal caused by the continuous probe laser to the PA-signal resulting from the pulsed pump laser using thallium bromoiodide (KRS-5) as sample material.