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1.
Prev Med ; 172: 107538, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37156430

RESUMO

Financial incentives are a controversial strategy for increasing vaccination. In this systematic review, we evaluated: 1) the effects of incentives on COVID-19 vaccinations; 2) whether effects differed based on study outcome, study design, incentive type and timing, or sample sociodemographic characteristics; and 3) the cost of incentives per additional vaccine administered. We searched PubMed, EMBASE, Scopus, and Econlit up to March 2022 for terms related to COVID, vaccines, and financial incentives, and identified 38 peer-reviewed, quantitative studies. Independent raters extracted study data and evaluated study quality. Studies examined the impact of financial incentives on COVID-19 vaccine uptake (k = 18), related psychological outcomes (e.g., vaccine intentions, k = 19), or both types of outcomes. For studies of vaccine uptake, none found that financial incentives had a negative effect on uptake, and most rigorous studies found that incentives had a positive effect on uptake. By contrast, studies of vaccine intentions were inconclusive. While three studies concluded that incentives may negatively impact vaccine intentions for some individuals, they had methodological limitations. Study outcomes (uptake versus intentions) and study design (experimental versus observational frameworks) appeared to influence results more than incentive type or timing. Additionally, income and political affiliation may moderate responses to incentives. Most studies evaluating cost per additional vaccine administered found that they ranged from $49-75. Overall, fears about financial incentives decreasing COVID-19 vaccine uptake are not supported by the evidence. Financial incentives likely increase COVID-19 vaccine uptake. While these increases appear to be small, they may be meaningful across populations. Registration: PROSPERO, CRD42022316086 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316086).


Assuntos
COVID-19 , Motivação , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Vacinação , Projetos de Pesquisa
2.
Methods ; 197: 20-29, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33164792

RESUMO

A number of peptides are known to bind lipid bilayer membranes and cause these natural barriers to leak in an uncontrolled manner. Though membrane permeabilizing peptides play critical roles in cellular activity and may have promising future applications in the therapeutic arena, significant questions remain about their mechanisms of action. The atomic force microscope (AFM) is a single molecule imaging tool capable of addressing lipid bilayers in near-native fluid conditions. The apparatus complements traditional assays by providing local topographic maps of bilayer remodeling induced by membrane permeabilizing peptides. The information garnered from the AFM includes direct visualization and statistical analyses of distinct bilayer remodeling modes such as highly localized pore-like voids in the bilayer and dispersed thinned membrane regions. Colocalization of distinct remodeling modes can be studied. Here we examine recent work in the field and outline methods used to achieve precise AFM image data. Experimental challenges and common pitfalls are discussed as well as techniques for unbiased analysis including the Hessian blob detection algorithm, bootstrapping, and the Bayesian information criterion. When coupled with robust statistical analyses, high precision AFM data is poised to advance understanding of an important family of peptides that cause poration of membrane bilayers.


Assuntos
Bicamadas Lipídicas , Peptídeos , Teorema de Bayes , Bicamadas Lipídicas/química , Microscopia de Força Atômica/métodos , Peptídeos/química , Imagem Individual de Molécula
3.
Nature ; 520(7546): 171-9, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25855454

RESUMO

Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.


Assuntos
Ciclo do Carbono , Mudança Climática , Pergelissolo/química , Regiões Árticas , Dióxido de Carbono/análise , Retroalimentação , Congelamento , Metano/análise , Água do Mar/química , Incerteza
4.
Food Policy ; 101: 102046, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-36570063

RESUMO

This article investigates how the shift from food-away-from-home and towards food-at-home at the onset of the COVID-19 pandemic affected the U.S. egg industry. We find that the pandemic increased retail and farm-gate prices for table eggs by approximately 141% and 182%, respectively. In contrast, prices for breaking stock eggs-which are primarily used in foodservice and restaurants-fell by 67%. On April 3, 2020, the FDA responded by issuing temporary exemptions from certain food safety standards for breaking stock egg producers seeking to sell into the retail table egg market. We find that this regulatory change rapidly pushed retail, farm-gate, and breaking stock prices towards their long-run pre-pandemic equilibrium dynamics. The pandemic reduced premiums for credence attributes, including cage-free, vegetarian-fed, and organic eggs, by as much as 34%. These premiums did not fully recover following the return to more "normal" price dynamics, possibly signaling that willingness-to-pay for animal welfare and environmental sustainability have fallen as consumers seek to meet basic needs during the pandemic. Finally, in spite of widespread claims of price gouging, we do not find that the pandemic (or the subsequent FDA regulatory changes) had a meaningful impact on the marketing margin for table eggs sold at grocery stores.

5.
Food Policy ; 101: 102072, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33846663

RESUMO

In this paper, we investigate the extent to which the presence of a large meatpacking (i.e., beef, pork, and broiler chicken) plant has affected county-level COVID-19 transmission dynamics. We find that-within 150 days after emergence of COVID-19 in a given county-the presence of a large beef packing facility increases per capita infection rates by 110%, relative to comparable counties without meatpacking plants. Large pork and chicken processing facilities increase transmission rates by 160% and 20%, respectively. While the presence of this type of industrial agricultural facility is shown to exacerbate initial disease transmission affecting large numbers of individuals in the community, over time daily case rates converge such that rates observed in meatpacking- and non-meatpacking counties become similar. In aggregate, results suggest that 334 thousand COVID-19 infections are attributable to meatpacking plants in the U.S. with associated mortality and morbidity costs totaling more than $11.2 billion.

6.
Econ Lett ; 209: 110097, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35153345

RESUMO

This research evaluates the effects of the twelve statewide vaccine lottery schemes that were announced as of June 7, 2021 on state vaccination rates. We construct a dataset that matches information on the timing and location of these lotteries with daily, county-level data from the U.S. Centers for Disease Control (CDC) on the cumulative number of people who have received at least one dose of an emergency-authorized Covid-19 vaccine. We find that 10 of the 12 statewide lotteries studied (i.e., all but Arkansas and California) generated a positive, statistically significant, and economically meaningful impact on vaccine uptake after thirty days. On average, the cost per marginal vaccination across these programs was approximately $55.

7.
Nature ; 475(7354): 86-90, 2011 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-21697831

RESUMO

Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.


Assuntos
Organismos Aquáticos/fisiologia , Ecossistema , Locomoção/fisiologia , Comportamento Predatório/fisiologia , Sistemas de Identificação Animal , Migração Animal , Animais , Teorema de Bayes , Biodiversidade , California , Clima , América do Norte , Oceano Pacífico , Dinâmica Populacional , Estações do Ano , Especificidade da Espécie , Movimentos da Água , Meio Selvagem
8.
Sci Rep ; 14(1): 22843, 2024 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353989

RESUMO

Surveys often estimate vaccination intentions using dichotomous ("Yes"/"No") or trichotomous ("Yes," "Unsure," "No") response options presented in different orders. Do survey results depend on these variations? This controlled experiment randomized participants to dichotomous or trichotomous measures of vaccine intentions (with "Yes" and "No" options presented in different orders). Intentions were measured separately for COVID-19, its booster, and influenza vaccines. Among a sample of U.S. adults (N = 4,764), estimates of vaccine intention varied as much as 37.5 ± 17.4 percentage points as a function of the dichotomous or trichotomous response set. Among participants who had not received the COVID-19 vaccine, the "Unsure" option was more likely to reduce the share of "No" (versus "Yes") responses, whereas among participants who had received the COVID-19 vaccine, the "Unsure" option was more likely to reduce the share of "Yes" (versus "No") responses. The "Unsure" category may increase doubt and decrease reliance on past vaccination behavior when forming intentions. The order of "Yes" and "No" responses had no significant effect. Future research is needed to further evaluate why the effects of including the "Unsure" option vary in direction and magnitude.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Intenção , Vacinação , Humanos , Masculino , Vacinação/estatística & dados numéricos , Feminino , Adulto , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/epidemiologia , Pessoa de Meia-Idade , Vacinas contra Influenza/administração & dosagem , Inquéritos e Questionários , SARS-CoV-2/imunologia , Adulto Jovem , Idoso , Adolescente , Influenza Humana/prevenção & controle
9.
Ann Oncol ; 23(8): 2185-2190, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22317770

RESUMO

BACKGROUND: Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES. PATIENTS AND METHODS: Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre-chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51). RESULTS: A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P=0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P=0.036). CONCLUSION: High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimens.


Assuntos
Antígenos de Neoplasias/biossíntese , Oxirredutases/biossíntese , Sarcoma de Ewing/imunologia , Adolescente , Adulto , Biomarcadores Tumorais/biossíntese , Membrana Celular/enzimologia , Membrana Celular/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sarcoma de Ewing/enzimologia , Adulto Jovem
10.
Biotechnol J ; 17(4): e2100373, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34873849

RESUMO

This paper assesses the economic value of genetically engineered (GE) Anopheles gambiae mosquitoes as a malaria control strategy. We use an epidemiological-economic model of malaria transmission to evaluate this technology for a range of village-level transmission settings. In each setting, we evaluate public health outcomes following introduction of GE mosquitoes relative to a "status quo" baseline scenario. We also assess results both in contrast to-and in combination with-a Mass Drug Administration (MDA) strategy. We find that-in low transmission settings-the present value (PV) public health benefits of GE mosquito release are substantial, both relative to status quo dynamics and MDA. In contrast, in high transmission settings, the release of GE mosquitoes may increase steady-state infection rates. Our results indicate that there are substantial policy complementarities when GE mosquito release is combined with local MDA-the combined control strategy can lead to local eradication.


Assuntos
Anopheles , Malária , Animais , Anopheles/genética , Malária/prevenção & controle
11.
Vaccine ; 40(51): 7451-7459, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-35914961

RESUMO

Experts debate whether COVID-19 vaccine mandates or financial incentives will reduce, rather than increase, interest in vaccination. Among 3,698 unvaccinated U.S. residents, we conducted a randomized, controlled survey-embedded experiment to estimate the absolute and relative psychological effects of vaccine policies specifying: mandates by employers or airlines, bars, and restaurants; lotteries for $1 million, $200,000, or $100,000; guaranteed cash for $1000, $200, or $100; and $1,000 as either a tax credit or penalty. Vaccine intention -the study outcome- predicts uptake and provides insight into the psychological mechanism that is most proximal to behavior (i.e., vaccination). Compared to controls, those who learned about the $1,000 cash reward policy were 17.1 (±5.3)% more likely to want vaccination. Employer mandates are more promising than other mandate policies (8.6 [+/- 7.4]% vs. 1.4 [+/- 6.0]%). The full results suggest that neither mandates nor financial incentives are likely to have counterproductive psychological effects. These policies are not mutually exclusive and, if implemented well, they may increase vaccine uptake.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Políticas , Vacinação , Hesitação Vacinal
12.
Vet Rec ; 190(9): e1389, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35122441

RESUMO

BACKGROUND: This research seeks to understand how the transition to a new generation of younger, more diverse farmers affects disease prevention efforts on UK farms. METHODS: We apply multivariate regression analysis to analyse survey responses from 112 Welsh cattle farm operators. RESULTS: Our results indicate that young farm operators (less than 40 years of age) receive less frequent visits from veterinarians. Further, farm operators who identify as female are less likely to screen and vaccinate against a range of diseases. Finally, both young farmers and female farm operators are less likely to achieve disease-free certification for various economically meaningful livestock diseases. CONCLUSION: One possible explanation for these outcomes is that female farm operators and young farmers may feel excluded from long-standing social networks in the farm animal health sector.


Assuntos
Criação de Animais Domésticos , Fazendeiros , Criação de Animais Domésticos/métodos , Animais , Bovinos , Demografia , Fazendas , Feminino , Humanos , Inquéritos e Questionários
13.
J Law Biosci ; 7(1): lsaa032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733690

RESUMO

Economic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing. One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions. Without legal intervention, some individuals will see socially risky behaviors as personally less costly than socially beneficial behaviors, a balance that makes those beneficial behaviors unsustainable. For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing noncompliant people are stymied. One mechanism is for policymakers to indemnify individuals for losses associated with taking those socially desirable behaviors to reduce the spread. We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms.

14.
Biochem Pharmacol ; 174: 113813, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31954717

RESUMO

P-glycoprotein (Pgp) is an ATP-dependent efflux transporter and plays a major role in anti-cancer drug resistance by pumping a chemically diverse range of cytotoxic drugs from cancerous tumors. Despite numerous studies with the transporter, the molecular features that drive anti-cancer drug efflux are not well understood. Even subtle differences in the anti-cancer drug molecular structure can lead to dramatic differences in their transport rates. To unmask these structural differences, this study focused on two closely-related anthracycline drugs, daunorubicin (DNR), and doxorubicin (DOX), with mouse Pgp. While only differing by a single hydroxyl functional group, DNR has a 4 to 5-fold higher transport rate than DOX. They both non-competitively inhibited Pgp-mediated ATP hydrolysis below basal levels. The Km of Pgp-mediated ATP hydrolysis extracted from the kinetics curves was lower for DOX than DNR. However, the dissociation constants (KDs) for these drugs determined by fluorescence quenching were virtually identical. Acrylamide quenching of Pgp tryptophan fluorescence to probe the tertiary structure of Pgp suggested that DNR shifts Pgp to a "closed" conformation, while DOX shifts Pgp to an "intermediate" conformation. The effects of these drugs on the Pgp conformational distributions in a lipid bilayer were also examined by atomic force microscopy (AFM). Analysis of AFM images revealed that DNR and DOX cause distinct and significant shifts in the conformational distribution of Pgp. The results were combined to build a conformational distribution model for anthracycline transport by Pgp.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antraciclinas/farmacologia , Antibióticos Antineoplásicos/farmacologia , Daunorrubicina/farmacologia , Doxorrubicina/farmacologia , Animais , Relação Dose-Resposta a Droga , Camundongos , Conformação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia
15.
Br J Cancer ; 101(1): 80-90, 2009 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-19491900

RESUMO

BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and many have been identified in heterologous model systems. METHODS: We have developed a stable RNA interference model knocking down EWS-FLI1 in the Ewing sarcoma cell line TC71. Gene expression analyses were performed to study the effect of RNA interference on the genetic signature of EWS-FLI1 and to identify genes that could contribute to tumourigenesis. RESULTS: EWS-FLI1 inhibition induced apoptosis, reduced cell migratory and tumourigenic capacities, and caused reduction in tumour growth. IGF-1 was downregulated and the IGF-1/IGF-1R signalling pathway was impaired. PBK/TOPK (T-LAK cell-originated protein kinase) expression was decreased because of EWS-FLI1 inhibition. We showed that TOPK is a new target gene of EWS-FLI1. TOPK inhibition prompted a decrease in the proliferation rate and a dramatic change in the cell's ability to grow in coalescence. CONCLUSION: This is the first report of TOPK activity in Ewing sarcoma and suggests a significant role of this MAPKK-like protein kinase in the Ewing sarcoma biology.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/biossíntese , Receptor IGF Tipo 1/metabolismo , Sarcoma de Ewing/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Regulação para Baixo , Feminino , Humanos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Proto-Oncogênica c-fli-1 , Interferência de RNA , Proteína EWS de Ligação a RNA , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/biossíntese , Receptor IGF Tipo 1/genética , Sarcoma de Ewing/enzimologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Science ; 162(3857): 1020-3, 1968 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-5725383

RESUMO

Data on pulmonary gas exchange were collected in breathhold dives to 90 feet in a tank and in open-sea breathhold dives to depths of 217.5 and 225 feet. Thoracic blood volume displacements were measured at depths of 25, 50, 90, and 130 feet, by use of the impedance plethysmograph. The open-sea dives were carried out with an average speed of descent of 3.95 feet per second and an average rate of ascent of 3.50 feet per second. End-dive alveolar oxygen tensions did not fall below 36 millimeters of mercury, while alveolar carbon dioxide tension did not rise above 40 millimeters of mercury except in one case. These findings indicate that for diver Croft, who has unusual lung capacity, neither hypoxia nor hypercapnia determined the depth limits under those conditions. At depths of 90 and 130 feet blood was forced into the thorax, amounting to 1047 and 850 milliliters respectively.


Assuntos
Volume Sanguíneo , Mergulho , Alvéolos Pulmonares/fisiologia , Tórax/irrigação sanguínea , Adaptação Fisiológica , Adulto , Dióxido de Carbono/sangue , Diurese , Humanos , Hipercapnia/fisiopatologia , Hiperventilação/fisiopatologia , Hipóxia/fisiopatologia , Masculino , Oxigênio/sangue , Consumo de Oxigênio , Pletismografia de Impedância , Espirometria
17.
Thromb Res ; 122(3): 366-75, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18308368

RESUMO

INTRODUCTION: Leptin is an adipocyte-derived cytokine primarily involved in the regulation of body weight and energy balance. In vivo studies suggest that leptin promotes platelet aggregation and thrombosis. Neutrophils are involved in the crosstalk between inflammation and thrombosis in clinical disorders. Leptin is also involved in the regulation of inflammation. AIM: We examined the in vitro effects of leptin on the expression of tissue factor (TF), the primary initiator of coagulation, in healthy neutrophils. MATERIALS AND METHODS/RESULTS: The effects on TF expression were assayed functionally using a modified prothrombin time (mPT), as well as at mRNA and protein levels. The same experiments were performed in parallel with PBMC. Leptin induced functional TF and increased TF mRNA and protein expression in both cell types, as determined by mPT, real-time RT-PCR, western blot, flow cytometry, immunocytochemistry. Inhibition studies revealed that the effect of leptin on TF expression is mediated, at least in part, by JAK2 and PI3K. Our findings, after neutralising TNFalpha in supernatants of leptin-treated cells, also suggest the involvement of TNFalpha in the leptin-induced TF expression in leukocytes. CONCLUSIONS: This study indicates a novel link between inflammation, obesity and thrombosis by showing that leptin is able to trigger the extrinsic coagulation cascade. This work suggests a possible mechanism of the thrombotic effects of hyperleptinemic-associated clinical disorders.


Assuntos
Janus Quinase 2/metabolismo , Leptina/imunologia , Leucócitos Mononucleares/enzimologia , Neutrófilos/enzimologia , Tromboplastina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Coagulação Sanguínea/fisiologia , Humanos , Inflamação/fisiopatologia , Leptina/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Obesidade/imunologia , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Tempo de Protrombina , RNA Mensageiro/metabolismo , Tromboplastina/genética , Trombose/imunologia , Trombose/metabolismo
18.
Oncogene ; 25(19): 2795-800, 2006 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-16314831

RESUMO

High CD99 expression levels and rearrangements of the EWS gene with ETS transcription factor genes characterize the Ewing's sarcoma family of tumors (ESFT). CD99 is a cell surface glycoprotein whose engagement has been implicated in cell proliferation as well as upregulation and transport of several transmembrane proteins in hematopoietic cells. In ESFT, antibody ligation of CD99 induces fast homotypic cell aggregation and cell death although its functional role in these processes remains largely unknown. Here, using an RNAi approach, we studied for the first time the consequences of modulated CD99 expression in six different ESFT cell lines, representing the most frequent variant forms of EWS gene rearrangement. CD99 suppression resulted in growth inhibition and reduced migration of ESFT cells. Among genes whose expression changes in response to CD99 modulation, the potassium-channel modulatory factor KCMF1 was consistently upregulated. In a series of 22 primary ESFT, KCMF1 expression levels inversely correlated with CD99 abundancy. Cells forced to express ectopic KCMF1 showed a similar reduction in migratory ability as CD99 silenced ESFT cells. Our results suggest that in ESFT, high CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells and identify KCMF1 as a potential metastasis suppressor gene downregulated by high constitutive CD99 expression in ESFT.


Assuntos
Antígenos CD/fisiologia , Neoplasias Ósseas/patologia , Moléculas de Adesão Celular/fisiologia , Sarcoma de Ewing/patologia , Ubiquitina-Proteína Ligases/metabolismo , Antígeno 12E7 , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Ensaio de Unidades Formadoras de Colônias , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Interferente Pequeno/farmacologia , Sarcoma de Ewing/metabolismo , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética , Regulação para Cima
19.
J Cancer Res Clin Oncol ; 133(10): 749-59, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17530287

RESUMO

Only few clinical factors predict the prognosis of patients with Ewing tumors. Unfavorable outcome is associated with primary metastatic disease, age > 15 years, tumor volume above 200 ml, and the histological response to chemotherapy. The aim of this study was to elucidate the prevalence and clinical impact of microsatellite instability (MSI) together with the relation between MSI and mismatch repair protein expression in Ewing tumors. DNA from 61 primary Ewing tumors and 11 Ewing tumor cell lines was extracted and microsatellite analysis for the detection of instability or loss of heterozygosity was performed for the five markers of the Bethesda panel BAT25, BAT26, D5S346, D2S123, and D17S250, which represents the established marker panel for the analysis of hereditary non-polyposis colorectal carcinoma (HNPCC) patients. In addition, single nucleotide repeat regions of the two tumor genes BAX and transforming growth factor receptor II (TGFBR2) were also included. All of the 61 samples were suitable for LOH analysis and 55 for the determination of MSI-status. LOH of these microsatellite markers was detected in 9 of the 61 patients (14.8%). Over all, genetic instability, i.e. MSI and/or LOH, was detected in 17 tumors (27.9%). One out of the 11 tumor cell lines (STA ET1) was characterized by instability of all the five Bethesda markers, while from primary tumor samples, only one showed MSI in more than one microsatellite marker (D5S346 and D17S250, MSI-high). Eight of the fifty-five patients (14.5%) showed instability of one microsatellite locus (MSI-low). No instability was detected in BAT26, D2S123, BAX and TGFBR2. There was no significant correlation between MSI and loss of expression of mismatch repair proteins MLH1, MSH2, or MSH6. The impairment of the p53 signaling pathway (expression of TP53 and/or MDM2 by immunohistochemistry) was significantly associated with reduced overall survival (15 of 49 patients (30.6%), P = 0.0410, log-rank test). We conclude that MSI is not prevalent in Ewing tumor and that the nature of instability differs from the form observed in colorectal carcinoma, the model tumor of MSI. This is documented by the different pattern of MSI (no BAT26 instability) in Ewing tumors and the lack of a strict correlation between MSI-high and loss of expression of MSH2, MSH6 and MLH1.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Instabilidade de Microssatélites , Proteína 2 Homóloga a MutS/biossíntese , Proteínas Nucleares/biossíntese , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Perda de Heterozigosidade , Proteína 1 Homóloga a MutL , Proteínas de Fusão Oncogênica/biossíntese , Reação em Cadeia da Polimerase , Proteína Proto-Oncogênica c-fli-1 , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/mortalidade , Análise de Sobrevida , Fatores de Transcrição/biossíntese , Proteína Supressora de Tumor p53/biossíntese
20.
Sci Rep ; 7: 45340, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28349947

RESUMO

This article exploits a method recently incorporated in the geometric morphometric toolkit that complements previous approaches to quantifying the facial features associated with specific body characteristics and trait attribution during social perception. The new method differentiates more globally encoded from more locally encoded information by a summary scaling dimension that is estimated by fitting a line to the plot of log bending energy against log variance explained, partial warp by partial warp, for some sample of varying shapes. In the present context these variances come from the regressions of shape on some exogenous cause or effect of form. We work an example involving data from male faces. Here the regression slopes are steepest, and the sums of explained variances over the uniform component, partial warp 1 and partial warp 2 are greatest, for the conventional body mass index, followed by cortisol and, lastly, perceived health. This suggests that physiological characteristics may be represented at larger scale (global patterns), whereas cues in perception are of smaller scale (local patterns). Such a polarity within psychomorphospace, the global versus the focal, now has a metric by which patterns of morphology can be modeled in both biological and psychological studies.


Assuntos
Face/fisiologia , Adolescente , Adulto , Índice de Massa Corporal , Face/anatomia & histologia , Feminino , Nível de Saúde , Humanos , Hidrocortisona/metabolismo , Masculino , Fotografação , Saliva/metabolismo , Adulto Jovem
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