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91.
Julie Nemecek Nabanita Nag Christina M. Carlson Jay R. Schneider Dennis M. Heisey Christopher J. Johnson David M. Asher Luisa Gregori 《PloS one》2013,8(10)
Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human and macaque blood. 相似文献
92.
93.
Luis Sebastian Contreras-Huerta Katharine S. Baker Katherine J. Reynolds Luisa Batalha Ross Cunnington 《PloS one》2013,8(12)
Recent studies have shown that perceiving the pain of others activates brain regions in the observer associated with both somatosensory and affective-motivational aspects of pain, principally involving regions of the anterior cingulate and anterior insula cortex. The degree of these empathic neural responses is modulated by racial bias, such that stronger neural activation is elicited by observing pain in people of the same racial group compared with people of another racial group. The aim of the present study was to examine whether a more general social group category, other than race, could similarly modulate neural empathic responses and perhaps account for the apparent racial bias reported in previous studies. Using a minimal group paradigm, we assigned participants to one of two mixed-race teams. We use the term race to refer to the Chinese or Caucasian appearance of faces and whether the ethnic group represented was the same or different from the appearance of the participant'' own face. Using fMRI, we measured neural empathic responses as participants observed members of their own group or other group, and members of their own race or other race, receiving either painful or non-painful touch. Participants showed clear group biases, with no significant effect of race, on behavioral measures of implicit (affective priming) and explicit group identification. Neural responses to observed pain in the anterior cingulate cortex, insula cortex, and somatosensory areas showed significantly greater activation when observing pain in own-race compared with other-race individuals, with no significant effect of minimal groups. These results suggest that racial bias in neural empathic responses is not influenced by minimal forms of group categorization, despite the clear association participants showed with in-group more than out-group members. We suggest that race may be an automatic and unconscious mechanism that drives the initial neural responses to observed pain in others. 相似文献
94.
Caribbean avifaunal biogeography has been mainly studied based on mitochondrial DNA. Here, we investigated both past and recent island differentiation and micro-evolutionary changes in the Zenaida Dove (Zenaida aurita) based on combined information from one mitochondrial (Cytochrome c Oxydase subunit I, COI) and 13 microsatellite markers and four morphological characters. This Caribbean endemic and abundant species has a large distribution, and two subspecies are supposed to occur: Z. a. zenaida in the Greater Antilles (GA) and Z. a. aurita in the Lesser Antilles (LA). Doves were sampled on two GA islands (Puerto Rico and the British Virgin Islands) and six LA islands (Saint Barthélemy, Guadeloupe, Les Saintes, Martinique, Saint Lucia and Barbados). Eleven COI haplotypes were observed that could be assembled in two distinct lineages, with six specific to GA, four to LA, the remaining one occurring in all islands. However, the level of divergence between those two lineages was too moderate to fully corroborate the existence of two subspecies. Colonisation of the studied islands appeared to be a recent process. However, both phenotypic and microsatellite data suggest that differentiation is already under way between all of them, partly associated with the existence of limited gene flow. No isolation by distance was observed. Differentiation for morphological traits was more pronounced than for neutral markers. These results suggest that despite recent colonisation, genetic drift and/or restricted gene flow are promoting differentiation for neutral markers. Variation in selective pressures between islands may explain the observed phenotypic differentiation. 相似文献
95.
Camila Gewehr Sara Marchesan Oliveira Mateus Fortes Rossato Gabriela Trevisan Gerusa Duarte Dalmolin Flávia Karine Rigo Célio José de Castro Júnior Marta Nascimento Cordeiro Juliano Ferreira Marcus V. Gomez 《PLoS neglected tropical diseases》2013,7(4)
Background
The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV).Methodology/Principal Findings
Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.). The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv), local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4) and vanilloid receptors (TRPV1). We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na+ channels, acid-sensitive ion channels (ASIC) and TRPV1 receptors.Conclusion/Significance
Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of interest not only for better treating poisoning by P. nigriventer but also appreciating the diversity of targets triggered by PNV toxins. 相似文献96.
María Belén Pisano Griselda Oria Geraldine Beskow Javier Aguilar Brenda Konigheim María Luisa Cacace Luis Aguirre Marina Stein Marta Silvia Contigiani 《PLoS neglected tropical diseases》2013,7(12)
Venezuelan equine encephalitis viruses (VEEV) are responsible for human diseases in the Americas, producing severe or mild illness with symptoms indistinguishable from dengue and other arboviral diseases. For this reason, many cases remain without certain diagnosis. Seroprevalence studies for VEEV subtypes IAB, ID, IF (Mosso das Pedras virus; MDPV), IV (Pixuna virus; PIXV) and VI (Rio Negro virus; RNV) were conducted in persons from Northern provinces of Argentina: Salta, Chaco and Corrientes, using plaque reduction neutralization test (PRNT). RNV was detected in all studied provinces. Chaco presented the highest prevalence of this virus (14.1%). Antibodies against VEEV IAB and -for the first time- against MDPV and PIXV were also detected in Chaco province. In Corrientes, seroprevalence against RNV was 1.3% in the pediatric population, indicating recent infections. In Salta, this was the first investigation of VEEV members, and antibodies against RNV and PIXV were detected. These results provide evidence of circulation of many VEE viruses in Northern Argentina, showing that surveillance of these infectious agents should be intensified. 相似文献
97.
Emilie Arnault Coralie Barrau Céline Nanteau Pauline Gondouin Karine Bigot Fran?oise Viénot Emmanuel Gutman Valérie Fontaine Thierry Villette Denis Cohen-Tannoudji José-Alain Sahel Serge Picaud 《PloS one》2013,8(8)
Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye. 相似文献
98.
Xiaofei Chang Eugene Izumchenko Luisa M. Solis Myoung Sook Kim Aditi Chatterjee Shizhang Ling Constance L. Monitto Paul M. Harari Manuel Hidalgo Steve N. Goodman Ignacio I. Wistuba Atul Bedi David Sidransky 《PloS one》2013,8(7)
The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate mechanisms of resistance to EGFR-targeted therapies in tumors that do not harbor TK sensitizing mutations in order to identify markers capable of guiding the decision to incorporate these drugs into chemotherapeutic regimens. Here we show that EGFR activity was markedly decreased during the evolution of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, with a concomitant increase of mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR through the upregulation of the PI3K-AKT pathway. EGFR activity, which was more accurately predicted by the ratio of Mig6/EGFR, highly correlated with erlotinib sensitivity in panels of cancer cell lines of different tissue origins. Blinded testing and analysis in a prospectively followed cohort of lung cancer patients treated with gefitinib alone demonstrated higher response rates and a marked increased in progression free survival for patients with a low Mig6/EGFR ratio (approximately 100 days, P = 0.01). 相似文献
99.
Johanna Aponte-González Luisa Fajardo-Bernal Jorge Diaz Javier Eslava-Schmalbach Oscar Gamboa Joel W. Hay 《PloS one》2013,8(11)
Objective
To compare costs and effectiveness of three strategies used against cervical cancer (CC) and genital warts: (i) Screening for CC; (ii) Bivalent Human Papillomavirus (HPV) 16/18 vaccine added to screening; (iii) Quadrivalent HPV 6/11/16/18 vaccine added to screening.Methods
A Markov model was designed in order to simulate the natural history of the disease from 12 years of age (vaccination) until death. Transition probabilities were selected or adjusted to match the HPV infection profile in Colombia. A systematic review was undertaken in order to derive efficacy values for the two vaccines as well as for the operational characteristics of the cytology test. The societal perspective was used. Effectiveness was measured in number of averted Disability Adjusted Life Years (DALYS).Results
At commercial prices reported for 2010 the two vaccines were shown to be non-cost-effective alternatives when compared with the existing screening strategy. Sensitivity analyses showed that results are affected by the cost of vaccines and their efficacy values, making it difficult to determine with certainty which of the two vaccines has the best cost-effectiveness profile. To be ‘cost-effective’ vaccines should cost between 141 and 147 USD (Unite States Dollars) per vaccinated girl at the most. But at lower prices such as those recommended by WHO or the price of other vaccines in Colombia, HPV vaccination could be considered very cost-effective.Conclusions
HPV vaccination could be a convenient alternative for the prevention of CC in Colombia. However, the price of the vaccine should be lower for this vaccination strategy to be cost-effective. It is also important to take into consideration the willingness to pay, budgetary impact, and program implications, in order to determine the relevance of a vaccination program in this country, as well as which vaccine should be selected for use in the program. 相似文献100.
Karine Briot Simon Paternotte Sami Kolta Richard Eastell Dieter Felsenberg David M. Reid Claus-C. Glüer Christian Roux 《PloS one》2013,8(12)