Structural and Functional Alterations in Mitochondria-Associated Membranes (MAMs) and in Mitochondria Activate Stress Response Mechanisms in an In Vitro Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events modulated by these subcellular domains. In this study, we characterized the structural and functional alterations at MAM, mitochondria, and ER/microsomes in a mouse neuroblastoma cell line (N2A) overexpressing the human amyloid precursor protein (APP) with the familial Swedish mutation (APPswe). Proteins levels were determined by Western blot, ER-mitochondria contacts were quantified by transmission electron microscopy, and Ca2+ homeostasis and mitochondria function were analyzed using fluorescent probes and Seahorse assays. In this in vitro AD model, we found APP accumulated in MAM and mitochondria, and altered levels of proteins implicated in ER-mitochondria tethering, Ca2+ signaling, mitochondrial dynamics, biogenesis and protein import, as well as in the stress response. Moreover, we observed a decreased number of close ER-mitochondria contacts, activation of the ER unfolded protein response, reduced Ca2+ transfer from ER to mitochondria, and impaired mitochondrial function. Together, these results demonstrate that several subcellular alterations occur in AD-like neuronal cells, which supports that the defective ER-mitochondria crosstalk is an important player in AD physiopathology.

Interventions to improve the quality of cataract services: protocol for a global scoping review.

INTRODUCTION: Cataract is the leading cause of blindness globally and a major cause of vision impairment. Cataract surgery is an efficacious intervention that usually restores vision. Although it is one of the most commonly conducted surgical interventions worldwide, good quality services (from being detected with operable cataract to undergoing surgery and receiving postoperative care) are not universally accessible. Poor quality understandably reduces the willingness of people with operable cataract to undergo surgery. Therefore, it is critical to improve the quality of care to subsequently reduce vision loss from cataract. This scoping review aims to summarise the nature and extent of the published literature on interventions to improve the quality of services for primary age-related cataract globally. METHODS AND ANALYSIS: We will search MEDLINE, Embase and Global Health for peer-reviewed manuscripts published since 1990, with no language, geographic or study design restrictions. To define quality, we have used the elements adopted by the WHO-effectiveness, safety, people-centredness, timeliness, equity, integration and efficiency-to which we have added the element of planetary health. We will exclude studies focused on the technical aspects of the surgical procedure and studies that only involve children (<18 years). Two reviewers will screen all titles/abstracts independently, followed by a full-text review of potentially relevant articles. For included articles, data regarding publication characteristics, study details and quality-related outcomes will be extracted by two reviewers independently. Results will be synthesised narratively and presented visually using a spider chart. ETHICS AND DISSEMINATION: Ethical approval was not sought, as our review will only include published and publicly accessible information. We will publish our findings in an open-access peer-reviewed journal and develop an accessible summary of the results for website posting. A summary of the results will be included in the ongoing Lancet Global Health Commission on Global Eye Health. REGISTRATION DETAILS: Open Science Framework (https://osf.io/8gktz).

Safe-by-Design of Glucan Nanoparticles: Size Matters When Assessing the Immunotoxicity.

Glucan (from Alcaligenes faecalis) is a polymer composed of ß-1,3-linked glucose residues, and it has been addressed in different medical fields, namely in nanotechnology, as a vaccine or a drug delivery system. However, due to their small size, nanomaterials may present new risks and uncertainties. Thus, this work aims to describe the production of glucan nanoparticles (NPs) with two different sizes, and to evaluate the influence of the NPs size on immunotoxicity. Results showed that, immediately after production, glucan NPs presented average sizes of 129.7 ± 2.5 and 355.4 ± 41.0 nm. Glucan NPs of 130 nm presented greater ability to decrease human peripheral blood mononuclear cells and macrophage viability and to induce reactive oxygen species production than glucan NPs of 355 nm. Both NP sizes caused hemolysis and induced a higher metabolic activity in lymphocytes, although the concentration required to observe such effect was lower for the 130 nm glucan NPs. Regarding pro-inflammatory cytokines, only the larger glucan NPs (355 nm) were able to induce the secretion of IL-6 and TNF-α, probably due to their recognition by dectin-1. This higher immunomodulatory effect of the larger NPs was also observed in its ability to stimulate the production of nitric oxide (NO) and IL-1ß. On the contrary, a small amount of Glu 130 NPs inhibited NO production. In conclusion, on the safe-by-design of glucan NPs, the size of the particles should be an important critical quality attribute to guarantee the safety and effectiveness of the nanomedicine.

Trends in thyroid cancer incidence and mortality in Portugal.

The objective was to quantify thyroid cancer incidence and mortality trends in Portugal. The number of thyroid cancer cases and incidence rates were retrieved from the Regional Cancer Registries for the period 1989-2011. The number of deaths and mortality rates were obtained from the WHO cancer mortality database (1988-2003 and 2007-2012) and Statistics Portugal (2004-2006; 1988-2012 by region). Joinpoint regression of the standardized incidence and mortality rates was performed. A significant, rapid and continued increase in incidence was observed for both sexes in each of the Regional Cancer Registries, with annual per cent changes (APCs) ranging between 2 and 9. Incidence in Portuguese women is higher than estimates for the world and Europe. Mortality decreased for women (APC: -1.5), with the greatest decrease in the North, and increased marginally for men (APC: +0.2), with a greater increase in the South. The significant increases in incidence in Portugal are predominantly because of the increase in incidence among women from the North. These trends, combined with an overall low mortality and high 5-year relative survival, raise concerns on the extent to which overdiagnosis may be taking place. Further research is needed, quantifying the importance of the most likely determinants of these trends as well as the extent and potentially deleterious effects of overdiagnosis and overtreatment in the Portuguese setting.

Inoculating Helianthus annuus (sunflower) grown in zinc and cadmium contaminated soils with plant growth promoting bacteria--effects on phytoremediation strategies.

Plant growth promoting bacteria (PGPR) may help reducing the toxicity of heavy metals to plants in polluted environments. In this work the effects of inoculating metal resistant and plant growth promoting bacterial strains on the growth of Helianthus annuus grown in Zn and Cd spiked soils were assessed. The PGPR strains Ralstonia eutropha (B1) and Chrysiobacterium humi (B2) reduced losses of weight in metal exposed plants and induced changes in metal bioaccumulation and bioconcentration - with strain B2 decreasing up to 67% Zn accumulation and by 20% Zn bioconcentration factor (BCF) in the shoots, up to 64% Zn uptake and 38% Zn BCF in the roots, and up to 27% Cd uptake and 27% Cd BCF in plant roots. The impact of inoculation on the bacterial communities in the rhizosphere of the plant was also assessed. Bacterial community diversity decreased with increasing levels of metal contamination in the soil, but in rhizosphere soil of plants inoculated with the PGPR strains, a higher bacterial diversity was kept throughout the experimental period. Inoculation of sunflower, particularly with C. humi (B2), appears to be an effective way of enhancing the short term stabilization potential of the plant in metal contaminated land, lowering losses in plant biomass and decreasing aboveground tissue contamination.

The effect of ectomycorrhizal fungi forming symbiosis with Pinus pinaster seedlings exposed to cadmium.

Cadmium is one of the most toxic heavy metals and its accumulation in the upper layers of forest soils affects plants, microorganisms and their interactions. Adequate strategies for the reforestation of metal contaminated sites are of vital importance. The aim of this work was to evaluate the response of Pinus pinaster seedlings to Cd exposure and to assess the effect of inoculation with two selected ectomycorrhizal fungi, Suillus bovinus and Rhizopogon roseolus on that response. Seedlings were exposed to soil contaminated at 15 and 30 mg Cd kg(-1). Shoot biomass of P. pinaster decreased ca. 36% when exposed to 15 mg Cd kg(-1). Overall, colonization by S. bovinus significantly enhanced shoot development up to 30% in contaminated soil while colonization by R. roseolus produced no significant effect at both Cd concentrations tested and significantly increased the level of Cd in the shoots at both Cd concentrations. Metal accumulation in the shoots and roots of non-inoculated and S. bovinus-inoculated seedlings increased at the higher Cd levels whereas R. roseolus-inoculated seedlings were not sensitive to Cd variation in the soil. The results from our research show that inoculation with ECM fungi has a significant impact on metal uptake and development of P. pinaster seedlings; the differential response induced by the two tested species highlights the importance of selecting the appropriate strains for nursery inoculation, and, as such, this biological tool ought to be considered in reforestation processes of heavy metal contaminated areas by woody species.

Arsenic, lead and nickel accumulation in Rubus ulmifolius growing in contaminated soil in Portugal.

This work investigates the potential of Rubus ulmifolius, indigenous to a metal contaminated site--Esteiro de Estarreja--for phytoremediation purposes. The site has a long history of metal contamination. The accumulation of lead (Pb), arsenic (As) and nickel (Ni) in different sections--roots, stems and leaves - of the plant was assessed and compared to the levels of those metals in the soil and in the available fraction. The distribution of metals throughout the area was quite heterogeneous, presenting levels of As, Pb and Ni of up to 3078, 1400 and 135 mg kg(-1), respectively, and the metal content in the sections of R. ulmifolius collected in the banks of the stream varied among sites of collection. Levels of metals were higher in the plant roots: As levels (mgkg(-1)) ranged from 277 to 1721 in the roots, 30 to 110 in the stems, and 60 to 265 in the leaves; Pb concentrations (mgkg(-1)) ranged from 248 to 1178 in the roots, 35 to 133 in the stems, and 25 to 149 in the leaves; and Ni (mgkg(-1)) ranged from 48 to 151 in the roots. Significant correlations were found between the total levels of Pb and As in the soil and the levels in the roots of the plant; further correlations between total and available levels in the soil and metals in other plant tissues were generally found as non-significant. According to the metal accumulation patterns of R. ulmifolius, this species seems to be valuable for application in phytostabilisation strategies.

Flutuação populacional de Willistoniella Mik e Ropalomera Wiedemann (Diptera: Ropalomeridae) na Amazônia Central / Populational fluctuation of Willistoniella Mik and Ropalomera Wiedemann (Diptera: Ropalomeridae) in the Central Amazonia

The populational fluctuation of flies of the genera Willistoniella Mik and Ropalomera Wiedemann (Diptera: Ropalomeridae) was studied using McPhail traps, with molasses (10%) as attractive bait, in two places in a mixed orchard of the families Myrtaceae, Sapotaceae, Anacardiaceae, Apocinaceaeand Gutiferae, during 13 months (december of 1996 to december of 1997) in the Central Amazonia, Brazil.The total of 1,148 Willistoniella flies and 99 Ropalomera flies were captured. The abundance observed in the genera was larger during the dry months, however there was no correlation between flies caught in the traps and the rainfall in the two places.

A flutuação populacional de moscas dos gêneros Willistoniella Mik e RopalomeraWiedemann (Diptera: Ropalomeridae) foi estudada utilizando-se armadilhas McPhail, com melaço de cana (10%) como isca, em dois lugares com pomar misto, com frutíferas das famílias Myrtaceae, Sapotaceae, Anacardiaceae, Apocinaceae e Gutiferae, durante 13 meses (dezembro de 1996 a dezembrode 1997) na Amazônia Central. Foram capturadas 1.148 moscas do gênero Willistoniella e 99 moscas de Ropalomera. A abundância observada nos gêneros foi maior durante os meses secos, entretanto não houve correlação entre o número de moscas capturadas nas armadilhas com a precipitação nos dois locais amostrados.