Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

A paradox of syntactic priming: why response tendencies show priming for passives, and response latencies show priming for actives

Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing

Cost risk benefit analysis to support chemoprophylaxis policy for travellers to malaria endemic countries

BACKGROUND: In a number of malaria endemic regions, tourists and travellers face a declining risk of travel associated malaria, in part due to successful malaria control. Many millions of visitors to these regions are recommended, via national and international policy, to use chemoprophylaxis which has a well recognized morbidity profile. To evaluate whether current malaria chemo-prophylactic policy for travellers is cost effective when adjusted for endemic transmission risk and duration of exposure. a framework, based on partial cost-benefit analysis was used. METHODS: Using a three component model combining a probability component, a cost component and a malaria risk component, the study estimated health costs avoided through use of chemoprophylaxis and costs of disease prevention (including adverse events and pre-travel advice for visits to five popular high and low malaria endemic regions) and malaria transmission risk using imported malaria cases and numbers of travellers to malarious countries. By calculating the minimal threshold malaria risk below which the economic costs of chemoprophylaxis are greater than the avoided health costs we were able to identify the point at which chemoprophylaxis would be economically rational. RESULTS: The threshold incidence at which malaria chemoprophylaxis policy becomes cost effective for UK travellers is an accumulated risk of 1.13% assuming a given set of cost parameters. The period a travellers need to remain exposed to achieve this accumulated risk varied from 30 to more than 365 days, depending on the regions intensity of malaria transmission. CONCLUSIONS: The cost-benefit analysis identified that chemoprophylaxis use was not a cost-effective policy for travellers to Thailand or the Amazon region of Brazil, but was cost-effective for travel to West Africa and for those staying longer than 45 days in India and Indonesia

Riparian ecotones and spatial variation of fish assemblages in Portuguese lowland streams

The first results of a long-term study on the role of riparian ecotones on the population and community dynamics of Iberian stream fish are presented and discussed . Riparian and macrophyte cover, bank slope and depth were among the most important variables affecting fish distribution . In general small fish favoured shallow areas with high macrophyte cover, whereas large fish dominated in deep areas with a high riparian cover . Slight spatial changes in terrestrial prey use were found suggesting a minor role for this resource during autumn . Finally, no significant spatial differences were found for linear growth, although some differences were obtained for the condition facto

Mitochondrial function in Parkinson's disease cybrids containing an nt2 neuron-like nuclear background

Mitochondria likely play a role in Parkinson's disease (PD) neurodegeneration. We modelled PD by creating cytoplasmic hybrid (cybrid) cell lines in which endogenous mitochondrial DNA (mtDNA) from PD or control subject platelets was expressed within human teratocarcinoma (NT2) cells previously depleted of endogenous mtDNA. Complex I activity was reduced in both PD cybrid lines and in the platelet mitochondria used to generate them. Under basal conditions PD cybrids had less ATP, more LDH release, depolarized mitochondria, less mitochondrial cytochrome c, and higher caspase 3 activity. Equivalent MPP+ exposures are more likely to trigger programmed cell death in PD cybrid cells than in control cybrid cells. Our data support a relatively upstream role for mitochondrial dysfunction in idiopathic PD

Developmental Defects of Enamel in Primary Teeth and Association with Early Life Course Events: A Study of 6--36 Month old Children in Manyara, Tanzania.

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).Focusing 6--36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child's early illness episodes and mothers' perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.22 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania

Environmental health : reflexions of the Brazilian Association of Post-Graduation in Collective Health - ABRASCO

O Brasil, apesar de sua extraordinária biodiversidade e do enorme potencial instalado para desenvolver ações integradas na temática do ambiente, não tem dado, do ponto de vista programático, a prioridade que o tema ambiente merece. A Associação Brasileira de Pós-Graduação em Saúde Coletiva-ABRASCO reconheceu a importância de organizar um Grupo Temático “Saúde e Ambiente” para, de maneira mais organizada, participar da luta pelo desenvolvimento sustentável, através da ação política no campo da saúde coletiva, em busca de ambientes saudáveis e da promoção da saúde. O objetivo principal deste Grupo Temático-GT foi contribuir para que o tema da saúde ambiental seja internalizado no campo da Saúde Coletiva. Método: O Grupo escolheu três eixos para discussão em uma oficina do V Congresso Brasileiro de Epidemiologia, em Curitiba, no ano de 2002. O resultado resultado do debate ocorrido foi apresentado segundo três eixos: identificação do campo teórico-conceitual em Saúde Ambiente; a política de saúde e ambiente; o caminho metodológico. A conclusão foi apresentada no formato de uma agenda do GT para o biênio 2002-2004. _______________________________________________________________________________________ ABSTRACTNot with standing its extraordinary biodiversity and enormous installed potential to develop actions integrated in to the topic of environmental health, Brazil has not given the environmental the priority the subject deserves from the programmatic, point of view. The Brazilian Association of Post-Graduation in Collective Health - ABRASCO recognized the importance of organizing a Thematic Group “Health and Environment” in order to, in a more organized fashion, participate in the struggle for sustainable development, through political action in collective health, oriented to wards health environments and health promotion. The main objective of this Thematic Group was to facilitate the subject of the environmental health to be internalized in to the field of the Collective Health. Method: The theme was debated in a workshop during the V Brazilian Congress of Epidemiology in Curitiba, in 2002. Results were presented according to three axes: 1- Identification of the theoretical-conceptual field in Environmental Health; 2- the politics of health and environment; 3- methodological route. The general conclusion was presented as an agenda for ABRASCO’s Thematic Group in Environmental Health for the biennial 2002-2004

Why Um Helps Auditory Word Recognition: The Temporal Delay Hypothesis

Several studies suggest that speech understanding can sometimes benefit from the presence of filled pauses (uh, um, and the like), and that words following such filled pauses are recognised more quickly. Three experiments examined whether this is because filled pauses serve to delay the onset of upcoming words and these delays facilitate auditory word recognition, or whether the fillers themselves serve to signal upcoming delays in a way which informs listeners' reactions. Participants viewed pairs of images on a computer screen, and followed recorded instructions to press buttons corresponding to either an easy (unmanipulated, with a high-frequency name) or a difficult (visually blurred, low-frequency) image. In all three experiments, participants were faster to respond to easy images. In 50% of trials in each experiment, the name of the image was directly preceded by a delay; in the remaining trials an equivalent delay was included earlier in the instruction. Participants were quicker to respond when a name was directly preceded by a delay, regardless of whether this delay was filled with a spoken um, was silent, or contained an artificial tone. This effect did not interact with the effect of image difficulty, nor did it change over the course of each experiment. Taken together, our consistent finding that delays of any kind help word recognition indicates that natural delays such as fillers need not be seen as ‘signals’ to explain the benefits they have to listeners' ability to recognise and respond to the words which follow them