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1.
J Econ Entomol ; 115(6): 1995-2003, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36209398

RESUMO

Spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), is an invasive pest of thin-skinned fruits in the United States. Monitoring traps are an integral part of SWD integrated pest management, allowing early detection and timely management of this pest. An ideal monitoring trap should be easy to use, effective in capturing SWD, sensitive and selective to male SWD which are easy to identify due to their spotted wings, and able to predict fruit infestation from trap captures. Deli-cup-based liquid traps (grower standard), which make in-situ observations difficult, were compared with red-panel sticky traps, both baited with commercial lures (Scentry, Trécé Broad-Spectrum (BS), and Trécé High-Specificity (HS)), across several US states in blueberries (lowbush and highbush), blackberry, raspberry, and cherry crops during 2018 and 2021. Results showed that red-panel traps effectively captured SWD, were able to detect male SWD early in the season while also being selective to male SWD all season-long, and in some cases linearly related male SWD trap captures with fruit infestation. Scentry and Trécé BS lures captured similar numbers of SWD, though Trécé BS and Trécé HS were more selective for male SWD in red panel traps than liquid traps in some cases. In conclusion, due to its ease of use with less processing time, red-panel traps are promising tools for detecting and identifying male SWD in-situ and for predicting fruit infestation. However, further research is needed to refine the trap captures and fruit infestation relationship and elucidate the trap-lure interactions in berry and cherry crops.


Assuntos
Mirtilos Azuis (Planta) , Rubus , Masculino , Animais , Drosophila , Frutas , Controle de Insetos/métodos , Produtos Agrícolas
2.
Pest Manag Sci ; 78(11): 4929-4938, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36054536

RESUMO

BACKGROUND: Invasive species threaten the productivity and stability of natural and managed ecosystems. Predicting the spread of invaders, which can aid in early mitigation efforts, is a major challenge, especially in the face of climate change. While ecological niche models are effective tools to assess habitat suitability for invaders, such models have rarely been created for invasive pest species with rapidly expanding ranges. Here, we leveraged a national monitoring effort from 543 sites over 3 years to assess factors mediating the occurrence and abundance of brown marmorated stink bug (BMSB, Halyomorpha halys), an invasive insect pest that has readily established throughout much of the United States. RESULTS: We used maximum entropy models to estimate the suitable habitat of BMSB under several climate scenarios, and generalized boosted models to assess environmental factors that regulated BMSB abundance. Our models captured BMSB distribution and abundance with high accuracy, and predicted a 70% increase in suitable habitat under future climate scenarios. However, environmental factors that mediated the geographical distribution of BMSB were different from those driving abundance. While BMSB occurrence was most affected by winter precipitation and proximity to populated areas, BMSB abundance was influenced most strongly by evapotranspiration and solar photoperiod. CONCLUSION: Our results suggest that linking models of establishment (occurrence) and population dynamics (abundance) offers a more effective way to forecast the spread and impact of BMSB and other invasive species than simply occurrence-based models, allowing for targeted mitigation efforts. Implications of distribution shifts under climate change are discussed. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Ecossistema , Heterópteros , Animais , Mudança Climática , Espécies Introduzidas , Dinâmica Populacional , Estados Unidos
3.
Artigo em Inglês | MEDLINE | ID: mdl-35711858

RESUMO

There are few cases in the current literature that describe simultaneous heart and kidney transplant (HKTx) while on total artificial heart (TAH) bridge therapy. We present a case of successful HKTx after 318 days on TAH bridge therapy and renal replacement therapy. This case demonstrates that TAH placement is a unique and up-and-coming option for bridging patients with heart and kidney failure to HKTx. TAH is a promising bridging option for patients who do not qualify for left ventricular assist device placement. The survival rates to heart transplant and long-term outcomes after heart transplant on TAH bridge therapy are encouraging as well. However, it is crucial for clinicians to be vigilant of the wide variety of complications associated with TAH when managing patients on TAH bridge therapy.

4.
Aging Ment Health ; 26(12): 2399-2406, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766526

RESUMO

OBJECTIVES: The current study investigated trait mindfulness associations with distinct aspects of executive function. We also aimed to characterize relationships between trait mindfulness with measures of psychological risk and resilience within adults aged 55-87 years. METHOD: In this cross-sectional study, 121 adults completed neuropsychological measures of working memory, mental set-shifting, and inhibition, as well as a battery of well-validated psychological self-report measures. The Mindful Attention Awareness Scale (MAAS) measured trait mindfulness. RESULTS: Trait mindfulness was associated with greater age, years of education and self-efficacy, and less perceived stress, depression, anxiety, and subjective cognitive concerns. Hierarchal multiple regression analyses showed that trait mindfulness was a significant predictor of inhibitory control, even after adjusting for age, education, and global cognition in the model. Trait mindfulness was not significantly associated with working memory or mental set-shifting. Follow-up analyses using the PROCESS macro revealed that trait mindfulness mediated the relationship between perceived stress and inhibitory control. CONCLUSION: Trait mindfulness was associated with measures of greater well-being and mental health. Our results also indicate that trait mindfulness may provide psychological resilience by attenuating perceived stress and enhancing the capacity to intentionally suppress irrelevant information and automatic responses.


Assuntos
Função Executiva , Atenção Plena , Humanos , Idoso , Estresse Psicológico/psicologia , Estudos Transversais , Atenção Plena/métodos , Cognição/fisiologia
5.
J Econ Entomol ; 114(4): 1666-1673, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34021561

RESUMO

Brown marmorated stink bug, Halyomorpha halys, is native to Asia and has invaded North America and Europe inflicting serious agricultural damage to specialty and row crops. Tools to monitor the spread of H. halys include traps baited with the two-component aggregation pheromone (PHER), (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, and pheromone synergist, methyl (2E,4E,6Z)-decatrienoate (MDT). Here, an international team of researchers conducted trials aimed at evaluating prototype commercial lures for H. halys to establish relative attractiveness of: 1) low and high loading rates of PHER and MDT for monitoring tools and attract and kill tactics; 2) polyethylene lure delivery substrates; and 3) the inclusion of ethyl (2E,4E,6Z)-decatrieonate (EDT), a compound that enhances captures when combined with PHER in lures. In general, PHER loading rate had a greater impact on overall trap captures compared with loading of MDT, but reductions in PHER loading and accompanying lower trap captures could be offset by increasing loading of MDT. As MDT is less expensive to produce, these findings enable reduced production costs. Traps baited with lures containing PHER and EDT resulted in numerically increased captures when EDT was loaded at a high rate, but captures were not significantly greater than those traps baited with lures containing standard PHER and MDT. Experimental polyethylene vial dispensers did not outperform standard lure dispensers; trap captures were significantly lower in most cases. Ultimately, these results will enable refinement of commercially available lures for H. halys to balance attraction and sensitivity with production cost.


Assuntos
Heterópteros , Feromônios , Animais , Europa (Continente) , Controle de Insetos , América do Norte , Estados Unidos
6.
J Econ Entomol ; 114(4): 1638-1646, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34021580

RESUMO

The invasive spotted-wing drosophila, Drosophila suzukii (Matsumura), is a key insect pest of berries globally, causing lost revenues and increased production costs associated with applications of insecticides. The insecticides utilized are commonly broad-spectrum pyrethroids, organophosphates, or carbamates in conventionally managed fields and spinosad in organically managed fields. Adoption of more selective insecticides has been limited due to their lower residual activity, and the requirement that some must be ingested to be effective. We investigated the use of feeding stimulants for D. suzukii as a method to improve longevity and efficacy in a range of insecticides. In laboratory bioassays, sugar increased the efficacy of all chemical classes tested; however, the inclusion of yeast only showed a benefit with malathion. Feeding stimulants had a limited effect in some cases under field conditions. Similarly, infestation in field plots and a semifield bioassay showed no significant decreases in infestation with the inclusion of feeding stimulants for the insecticides tested in these trials. We discuss the implications of these findings for managing D. suzukii in fruit crops to help ensure the harvest of marketable fruit.


Assuntos
Inseticidas , Animais , Drosophila , Frutas , Controle de Insetos , Malation
7.
Insects ; 11(11)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153021

RESUMO

Drosophila suzukii is a severe economic invasive pest of soft-skinned fruit crops. Management typically requires killing gravid adult female flies with insecticides to prevent damage resulting from oviposition and larval development. Fruits from cultivated and uncultivated host plants are used by the flies for reproduction at different times of the year, and knowledge of D. suzukii seasonal host plant use and movement patterns could be better exploited to protect vulnerable crops. Rearing and various marking methodologies for tracking movement patterns of D. suzukii across different landscapes have been used to better understand host use and movement of the pest. In this study, we report on potential to determine larval host for adult D. suzukii using their fatty acid profile or signature, and to use larval diet as an internal marker for adult flies in release-recapture experiments. Fatty acids can pass efficiently through trophic levels unmodified, and insects are constrained in the ability to synthesize fatty acids and may acquire them through diet. In many holometabolous insects, lipids acquired in the larval stage carry over to the adult stage. We tested the ability of a machine learning algorithm to discriminate adult D. suzukii reared from susceptible small fruit crops (blueberry, strawberry, blackberry and raspberry) and laboratory diet based on the fatty acid profile of adult flies. We found that fatty acid components in adult flies were significantly different when flies were reared on different hosts, and the machine learning algorithm was highly successful in correctly classifying flies according to their larval host based on fatty acid profile.

8.
J Econ Entomol ; 113(1): 159-171, 2020 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-31502635

RESUMO

Reliable monitoring of the invasive Halyomorpha halys abundance, phenology and geographic distribution is critical for its management. Halyomorpha halys adult and nymphal captures on clear sticky traps and in black pyramid traps were compared in 18 states across the Great Lakes, Mid-Atlantic, Southeast, Pacific Northwest and Western regions of the United States. Traps were baited with commercial lures containing the H. halys pheromone and synergist, and deployed at field sites bordering agricultural or urban locations with H. halys host plants. Nymphal and adult captures in pyramid traps were greater than those on sticky traps, but captures were positively correlated between the two trap types within each region and during the early-, mid- and late season across all sites. Sites were further classified as having a low, moderate or high relative H. halys density and again showed positive correlations between captures for the two trap types for nymphs and adults. Among regions, the greatest adult captures were recorded in the Southeast and Mid-Atlantic on pyramid and sticky traps, respectively, with lowest captures recorded in the West. Nymphal captures, while lower than adult captures, were greatest in the Southeast and lowest in the West. Nymphal and adult captures were, generally, greatest during July-August and September-October, respectively. Trapping data were compared with available phenological models showing comparable population peaks at most locations. Results demonstrated that sticky traps offer a simpler alternative to pyramid traps, but both can be reliable tools to monitor H. halys in different geographical locations with varying population densities throughout the season.


Assuntos
Heterópteros , Animais , Ninfa , Feromônios , Densidade Demográfica , Estações do Ano , Estados Unidos
9.
Insects ; 10(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835648

RESUMO

The herbivorous brown marmorated stink bug, Halyomorpha halys, has spread globally, and one of its key parasitoids, Trissolcus japonicus, has recently been detected in the pest's introduced range. For an exotic natural enemy to impact its targeted host in a novel environment, it must disperse, locate hosts, and potentially be redistributed to susceptible sites. Through intentionally releasing T. japonicus across four Oregon eco-regions, we investigated an introduced parasitoid's dispersal capacity in urban sites and in two perennial crops, hazelnut and raspberry. In a second paired field and laboratory study, we investigated T. japonicus survival in different plant materials. Within three days of release, adult T. japonicus located host egg masses at 45% of sites and, one year later, were detected at 40% of release sites. Areas where released wasps survived winter were mostly urban or semi-natural. In commercial crop release experiments, we recovered the highest percentage of wasps in raspberry within 5 m of the release site but found no statistical difference in dispersal distance with some wasps dispersing up to 50 m. Adult parasitoids survived up to 16 weeks outdoors in the winter, with greater survival over time in bark compared to leaf litter. Wasp survival remained above 50% over the course of a simulated winter environment without precipitation. Our work affirms the continuation of H. halys parasitism by T. japonicus in novel environments and provides insight into the high population sizes necessary to survive winter and locate host egg masses the following season.

10.
J Econ Entomol ; 112(5): 2077-2084, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31115460

RESUMO

The spread of adventive Trissolcus japonicus (Ashmead, 1904) populations in North America is anticipated to increase biological control of Halyomorpha halys (Stål; Hemiptera: Pentatomidae), the brown marmorated stink bug. In an agricultural context, biological control will succeed if it can be integrated in an environment with insecticide applications. We investigated T. japonicus compatibility with nine conventional and organic insecticides commonly used in integrated pest management in perennial crops. Through evaluating mortality and longevity in field and laboratory trials, we determined that T. japonicus fares poorly when exposed to residues of neonicotinoids and pyrethroids. Spinosad resulted in the highest percentage of T. japonicus mortality, 100% in the laboratory and 97% in a field trial. The anthranilic diamide, chlorantraniliprole, had the lowest lethality, with no differences compared to an untreated control. Trissolcus japonicus survived insecticide applications in hazelnut orchards, and over 50% of wasps remained alive after contact with the anthranilic diamides, chlorantraniliprole and cyantraniliprole, the biopesticide Chromobacterium, and an untreated control. Our results indicate that T. japonicus is unlikely to survive and parasitize H. halys in settings that coincide with broad-spectrum insecticide application. Future T. japonicus redistributions could continue in orchards treated with anthranilic diamides and Chromobacterium. As H. halys is a landscape-level pest, orchards may also benefit from biological control if T. japonicus are released in unsprayed areas adjacent to agriculture and in urban sites.


Assuntos
Heterópteros , Inseticidas , Vespas , Animais , América do Norte , Óvulo
11.
Bioinspir Biomim ; 10(5): 056007, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26334174

RESUMO

The directional properties of bat ears as receivers is a current area of interest in ultrasound research. This paper presents a new approach to analyse the relationship between morphological features and acoustical properties of the external ear of bat species. The beam pattern of Rousettus leschenaultii's right ear is measured and compared to that of receiver structures whose design is inspired by the bat ear itself and made of appropriate geometric shapes. The regular shape of these receivers makes it possible to control the key reception parameters and thus to understand the effect on the associated beam pattern of the parameters themselves. Measurements show one receiver structure has a beam pattern very similar to that of R. leschenaultii's ear, thus explaining the function of individual parts constituting its ear. As it is applicable to all bat species, this approach can provide a useful tool to investigate acoustics in bats, and possibly other mammals.


Assuntos
Quirópteros/anatomia & histologia , Quirópteros/fisiologia , Orelha Externa/anatomia & histologia , Orelha Externa/fisiologia , Ecolocação/fisiologia , Modelos Biológicos , Animais , Simulação por Computador , Modelos Anatômicos , Espalhamento de Radiação , Som
14.
Transl Oncogenomics ; 2: 85-97, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-23645983

RESUMO

Urokinase-type plasminogen activator (uPA) is associated with cancer recurrence where the most evidence comes from studies in breast cancer. According to the European Organization for Research and Treatment of Cancer, uPA is considered one of the most prominent biomarkers for cancer recurrence and therefore new agents are needed to inhibit it. Whether uPA is also expressed in pediatric cancers is yet unknown. If it is then uPA inhibitors might also help children with recurrent cancers. In this study, we addressed whether the integrin-linked kinase inhibitor (ILK), QLT0267, could suppress uPA. We previously showed that uPA expression is maximally inhibited when both the Akt and MAP kinase pathways were blocked which we anticipated can be achieved via QLT0267. In MDA-MB-231 breast cancer cells, QLT0267 blocked signaling through Akt and MAP kinase with a correlative decrease in uPA protein and mRNA, which corresponded to an inhibition of c-Jun phosphorylation. Consistent with these findings, cellular invasion was inhibited with either QLT0267 or with small interfering RNA against ILK. We then questioned whether uPA was commonly expressed in childhood sarcomas and if QLT0267 might be effective in this setting. We determined for the first time that uPA was highly expressed in rhabdomyosarcomas (RMS), but not Ewings sarcomas by screening cell lines (n = 31) and patient samples (n = 200) using Affymetrix microarrays. In alveolar RMS (ARMS) cell lines, QLT0267 blocked cell signaling, uPA production, invasion and ultimately survival. We concluded that QLT0267 blocks the production of uPA providing a new target for the management of recurrent cancers.

15.
Psychosom Med ; 68(6): 966-75, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17132842

RESUMO

OBJECTIVE: To identify possible hormonal factors involved in the differential responses to chemotherapy observed in our tumor model, we investigated if the timing among tumor cell injection, rehousing, and chemotherapy administration differentially affects levels of corticosterone (CORT), growth hormone (GH), and testosterone and tumor and host responses to chemotherapy. METHODS: Mice were reared either individually (I) or in groups (G). At 2 to 4 months, mice were injected with tumor cells and retained in their original housing conditions or rehoused into different experimental groups (GG, IG, II, GI) either immediately (experiment 1) or 14 days later (experiment 2); chemotherapy was administered when tumors weighed approximately 0.8 g. RESULTS: In experiment 1, IG and GG mice had better responses to chemotherapy than GI mice. Chemotherapy increased CORT levels in II mice and decreased GH levels in GI mice compared with those of their drug vehicle-treated counterparts. Under the temporal conditions of experiment 2, IG and GG mice lost the advantage seen in experiment 1 in terms of tumor and host responses to chemotherapy. Before chemotherapy administration, CORT levels in IG mice and GH levels in GI mice were higher than those in mice in all other housing conditions. At 1 day after chemotherapy, CORT levels were higher for chemotherapy-treated than for drug vehicle-treated IG mice, and at 5 days post chemotherapy, GH levels were higher in GI than in IG mice. CONCLUSIONS: Temporal relationships among tumor cell injection, rehousing, and chemotherapy administration critically influence responses to chemotherapy; these effects may be mediated, in part, by alterations in hormone levels.


Assuntos
Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/psicologia , Estresse Psicológico , Animais , Antineoplásicos/uso terapêutico , Corticosterona/sangue , Hormônio do Crescimento/sangue , Abrigo para Animais , Masculino , Neoplasias Mamárias Experimentais/sangue , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Testosterona/sangue , Fatores de Tempo
16.
Breast Cancer Res Treat ; 94(1): 47-52, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16172791

RESUMO

Elevated urokinase-type plasminogen activator (uPA) expression in breast tumors predicts poor survival. We found celecoxib (25 microM) significantly reduced uPA protein and mRNA in MDA-MB-231 breast cancer cells following 72 h of treatment. Celecoxib also inhibited cell viability (12.5 and 25 microM) and induced G2M arrest (25 microM). Therefore, celecoxib therapy for uPA positive breast cancer should be explored.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/farmacologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/genética
17.
Biochemistry ; 44(16): 6092-100, 2005 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-15835898

RESUMO

Cytochrome c(550) of the photosystem II complex of cyanobacteria is an unusual member of the large protein family of monoheme c-type cytochromes. Despite the fact that it shares considerable amino acid sequence similarity and has a protein fold similar to the other members of the family, Cyt.c(550) has a midpoint potential (E(m7) = -250 mV) that is much lower than the positive midpoint potentials characteristic (E(m7) = 100-300mV) of this cytochrome family. An E. coli heterologous expression system involving secretion of the recombinant protein from Synechocystis PCC6803 to the periplasm was utilized to allow production of wild-type and mutant forms of the cytochrome. For most of the variants studied, the yield of protein was significantly enhanced by growth at 28 degrees C and inclusion of sucrose and betaine, in addition to isopropyl-beta-d-thiogalactoside (IPTG), to the growth medium of the E. coli expression host. Analysis of the protein products revealed that the wild-type protein maintained the redox and visible spectroscopic characteristics of the authentic protein. Mutations in the residues engaging in hydrogen bond interactions with the heme propionate (Asn49) and the axial 6th ligand His92 (Pro93) resulted in small (12-20 mV), but reproducible, upshifts in midpoint redox potential. Substitution of the axial ligand His92 with Met produced no discernible changes in the optical spectrum relative to the wild-type despite the fact that in this mutant, unlike the others studied here, the thioether linkage either was not formed or was highly labile as evidenced by loss of the heme during SDS-PAGE. On the other hand, the midpoint potential of the C550-H92M mutant was upshifted by approximately 70 mV. This value is significantly less of a perturbation than that observed in a similar mutant that is natively expressed in Thermosynechoccocus but appears to have an intact thioether linkage between the heme and the polypeptide moiety.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Grupo dos Citocromos c/química , Grupo dos Citocromos c/genética , Complexo de Proteína do Fotossistema II/química , Synechocystis/química , Synechocystis/genética , Sequência de Bases , DNA Bacteriano/genética , Expressão Gênica , Genes Bacterianos , Heme/química , Potenciais da Membrana , Modelos Moleculares , Mutagênese Sítio-Dirigida , Oxirredução , Complexo de Proteína do Fotossistema II/genética , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Espectrofotometria
18.
Biochemistry ; 43(44): 14161-70, 2004 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-15518566

RESUMO

The H(2)O oxidizing domain of the cyanobacterial photosystem II (PSII) complex contains a low potential, c-type cytochrome termed c(550) that is essential for the in vivo stability of the PSII complex. A mutant lacking cytochrome c(550) (DeltapsbV) in Synechocystis sp. PCC6803 has been further analyzed together with a construct in which the distal axial heme iron ligand, histidine 92, has been substituted with a methionine (C550-H92M). Heme staining of SDS-PAGE showed that the C550-H92M mutation did not disturb the accumulation and heme-binding properties of the cytochrome. In DeltapsbV cells, the number of charge separating PSII centers was estimated to be 56% of the wild type, but of the existing centers, 33% lacked photooxidizable Mn ions. C550-H92M did not discernibly affect the intrinsic PSII electron-transfer kinetics compared to the wild type nor did it exhibit a significant fraction of centers lacking photooxidizable Mn; however, the number of charge separating PSII centers in mutant cells was 69% of the wild type. C550-H92M lost photoautotrophic growth ability in the absence of Ca(2+), but its growth was not affected by depletion of Cl(-), which differs from DeltapsbV. Taken together, the results suggest that in the absence of cytochrome c(550) electron transfer on the donor side is retarded perhaps at the level of Y(z) to P680(+) transfer, the heme ligand. His92 is not absolutely required for assembly of functional PSII centers; however, replacement by methionine prevents normal accumulation of PSII centers in the thylakoid membranes and alters the Ca(2+) requirement of PSII. The results are discussed in terms of current understanding of the Ca(2+) site of PSII.


Assuntos
Grupo dos Citocromos c/genética , Mutagênese Sítio-Dirigida , Complexo de Proteína do Fotossistema II/genética , Synechocystis/enzimologia , Synechocystis/genética , Substituição de Aminoácidos/genética , Cálcio/química , Grupo dos Citocromos c/química , Grupo dos Citocromos c/metabolismo , Fluorometria , Heme/química , Histidina/genética , Ligantes , Metionina/genética , Oxigênio/metabolismo , Fotólise , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/metabolismo , Polarografia , Synechocystis/metabolismo , Tilacoides/enzimologia , Tilacoides/genética
19.
Cancer Res ; 64(12): 4148-54, 2004 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15205325

RESUMO

BRCA1 has been implicated in a number of cellular processes, including transcriptional regulation, DNA damage repair, cell cycle arrest, and apoptosis. We identified mitogen-activated protein kinase (MAPK) kinase kinase 3 (MEKK3), an upstream regulator of the c-Jun NH(2)-terminal kinase/stress-activated protein kinase and p38/MAPK pathways, as a novel BRCA1-interacting protein in a yeast two-hybrid screen and confirmed the interaction by coimmunoprecipitation in mammalian cells. Deletion mapping demonstrated that amino acids 1611-1863 are required to mediate the interaction with MEKK3 in yeast. BRCA1 disease-associated mutations abrogated the interaction in yeast, and BRCA1 failed to interact with MEKK3 in BRCA1 mutant HCC1937 breast cancer cells. We demonstrate that small interfering RNA-based inhibition of endogenous BRCA1 reduces MEKK3 kinase activity and conversely that inducible expression of BRCA1 activates MEKK3 and p38/MAPK. Finally, we demonstrate using complementary approaches that BRCA1 is required for paclitaxel-induced activation of MEKK3. These data indicate that BRCA1 is a key regulator of the paclitaxel-induced stress response pathway and suggest that the ability of BRCA1 to associate with, and mediate the activation of, MEKK3 represents a potential mechanism through which this pathway is regulated.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteína BRCA1/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Paclitaxel/farmacologia , Proteína BRCA1/biossíntese , Proteína BRCA1/genética , Sítios de Ligação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Humanos , MAP Quinase Quinase Quinase 3 , Plasmídeos/genética , Estrutura Terciária de Proteína
20.
Cancer Res ; 64(1): 286-91, 2004 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-14729636

RESUMO

Urokinase plasminogen activator (uPA) expression in breast cancer is associated with relapse and a reduction in disease-specific survival. Thus, efforts are under way to identify uPA inhibitors. By screening a chemical library of >1000 compounds, 17-allyaminogeldanamycin (17AAG) was identified as a potent inhibitor of uPA by the National Cancer Institute and is now in Phase I clinical trials. At this time, it remains unclear how 17AAG blocks uPA; one possibility is through disruption of the insulin-like growth factor I receptor (IGF-IR) pathway. This would be consistent with studies from our laboratory showing that activation of IGF-IR results in the induction of uPA protein. In the study described herein, we observed that IGF-IR and uPA were highly expressed in 87 and 55% of breast cancer by screening tumor tissue microarrays representing 930 cases. A significant proportion (52.1% = 354 of 680 cases, P < 0.0001) of the patients had tumors expressing both proteins. uPA alone (P = 0.033) or in combination with IGF-IR (P = 0.0104) was indicative of decreased disease-specific survival. Next, we demonstrated that treating MDA-MB-231 cells with increasing concentrations of 17AAG resulted in IGF-IR degradation (IC(50) = 1.0 micro M) and blocked signal transduction through the Akt and mitogen-activated protein kinase pathways. Finally, we found that 17AAG had a robust inhibitory effect on the production of uPA mRNAand protein in the presence of IGF-I. Thus, our study raises the possibility that 17AAG could prove to be an effective therapeutic agent for a large number of breast cancer patients by inhibiting the IGF-IR and ultimately uPA.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Receptor IGF Tipo 1/genética , Rifabutina/análogos & derivados , Rifabutina/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/genética , Antineoplásicos/uso terapêutico , Sequência de Bases , Benzoquinonas , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Primers do DNA , Feminino , Seguimentos , Humanos , Lactamas Macrocíclicas , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , RNA Mensageiro/genética , Análise de Sobrevida , Fatores de Tempo , Células Tumorais Cultivadas
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