Composição e abundância de macrófitas num troço do rio Ovelha

As macrófitas fluviais são um grupo relevante para a avaliação ecológica dos rios. Numa amostragem realizada num troço de 100 m do rio Ovelha, localizado a 217 m de altitude, na freguesia de Fornos, Marco de Canaveses, estudou-se a abundância, composição e distribuição das macrófitas. Verificou-se que o troço estudado é pobre em macrófitas, apresentando uma riqueza específica baixa, o que poderá estar relacionado, sobretudo, com o substrato rochoso. Considerando os resultados obtidos é fundamental que, futuramente, sejam estudadas as macrófitas conjuntamente com outros elementos biológicos, no sentido de se proceder a uma correta monitorização do estado ecológico do rio Ovelha.info:eu-repo/semantics/publishedVersio

G2019S dardarin substitution is a common cause of Parkinson's disease in a Portuguese cohort

LRRK2 mutations have recently been described in families with Parkinson's disease. Here we show that one of them (G2019S) is present in 6% (7 of 124) unrelated cases of disease in a clinic-based sample series from central Portugal, but not present in 126 controls from the same population. Thus, LRRK2 mutations appear to be a common cause of typical Parkinson's disease and as such will alter clinical practice. © 2005 Movement Disorder Societ

Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates

Summary: Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells’ proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies

Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2′-bipy-4,4′-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3–14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy

Biotinylated polymer-ruthenium conjugates: in vitro and in vivo studies in a triple-negative breast cancer model

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2'-bipy-4,4'-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3-14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy.This work was funded by Fundação para a Ciência e a Tecnologia (FCT), I.P./MCTES through national funds (PIDDAC)—UIDB/00100/2020 and LA/P/0056/2020. This work was also funded in the scope of the project PTDC/QUI-QIN/28662/2017 (FCT). Andreia Valente acknowledges CEEC-IND 2017 (CEECIND/01974/2017; acknowledging FCT, as well as POPH and FSE—European Social Fund). Leonor Côrte-Real, Ana Rita Brás and Adhan Pilon thank FCT for their Ph.D. Grants (SFRH/BD/100515/2014, SFRH/BD/139271/2018 and SFRH/BD/139412/2018, respectively)

Anthocyanin-Related Pigments: Natural Allies for Skin Health Maintenance and Protection

Human skin is commonly described as a particularly dynamic and complex environment, with a physiological balance continuously orchestrated by numerous internal and external factors. Intrinsic aging, exposure to UV radiation and skin pathogens are some of the key players that account for dermatological alterations and ailments. In this regard, this study intended to explore the potential skin-health beneficial properties of a group of molecules belonging to the anthocyanin family: cyanidin- and malvidin-3-O-glucosides and some of their structurally related pigments, resulting in a library of compounds with different structural properties and color hues. The inclusion of both purified compounds and crude extracts provided some insights into their distinctive effects when tested as individual agents or as part of multicomponent mixtures. Overall, most of the compounds were found to reduce biofilm production by S. aureus and P. aeruginosa reference strains, exhibit UV-filter capacity, attenuate the production of reactive oxygen species in human skin keratinocytes and fibroblasts and also showed inhibitory activity of skin-degrading enzymes, in the absence of cytotoxic effects. Carboxypyranocyanidin-3-O-glucoside stood out for its global performance which, combined with its greater structural stability, makes this a particular interesting compound for potential incorporation in topical formulations. Results provide strong evidence of the skin protective effects of these pigments, supporting their further application for cosmeceutical purposes

Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP

Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer’s disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early onset AD (mean age at onset of 52.9 years; range 31– 64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d’Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new nonsynonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations