Transthyretin mutagenesis: impact on amyloidogenesis and disease

Funding This work was supported by COMPETE and CENTRO-202010. 13039/501100011929 and by Fundação para a Ciência e a Tecnologia (FCT) through grants UIDB/00313/2020 and UIDP/00313/2020 (to Coimbra Chemistry Center, University of Coimbra) and doctoral fellowship SFRH/BD/137991/2018 (to Z.L.A.).Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. “Hot spot” mutation regions are mainly assigned to β-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various in vitro TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset.info:eu-repo/semantics/publishedVersio

Validation of a suggested pre-operative protocol for the prevention of traumatic dental injuries during oroendotracheal intubation: a pilot study

The aim of this study was to develop a protocol for oral pre-operative registration and dental risk assessment by the anaesthesiologist, determining its reliability through the inter-observer agreement between a senior dental student and an internal physician specializing in anaesthesiology. A convenience sample consisting of 35 patients was selected. These were observed during the anaesthesiology consultation, at Hospital de São João, Porto, Portugal. The protocol included a self-administered questionnaire and a brief clinical examination by the two observers. A descriptive analysis (qualitative and quantitative variables) was performed. The Fleiss Kappa index was used to measure the degree of agreement between the two observers. In most of the parameters defined, the agreement presented Kappa index values between 0.6 and 1, corresponding to good and excellent correlation, respectively. The general oral status was considered “poor”, with a great number of missing teeth, namely the upper central and lateral incisors. The proposed pre-anaesthetic protocol can be a reliable tool for the anaesthesiologists, which suggests the relevancy of incorporating interdisciplinary training between future health professionals. Further research is needed to assess its implementation, providing information about the pre-operative oral status, preventing intraoperative damage and potential medicolegal litigation

Low-Protein Diets, Malnutrition, and Bone Metabolism in Chronic Kidney Disease

This article belongs to the Special Issue The Role of Dietary Patterns in Malnutrition – Relevance of Body Weight upon Non-communicable Diseases.Chronic kidney disease (CKD) has a high prevalence worldwide, with increasing incidence in low- and middle-income countries, and is associated with high morbidity and mortality, particularly from cardiovascular disease. Protein-restricted diets are one of the most widely used non-pharmacological approaches to slow the progression of CKD and prevent associated metabolic abnormalities. However, some concerns have been raised about the long-term safety of these diets, particularly with regard to patients’ nutritional status and bone and mineral disorders. Therefore, the aim of this article is to review the most recent scientific evidence on the relevance of using protein-restricted diets (with or without keto-analogue supplementation) and, in particular, their relationships with malnutrition and mineral and bone disorders in people with CKD without kidney replacement therapies. Although protein-restricted diets, especially when supplemented with keto-analogues and highly personalized and monitored, do not appear to be associated with malnutrition, research on their effects on bone and mineral disorders is scarce, deserving further investigation.info:eu-repo/semantics/publishedVersio

BSA-PEG Hydrogel: A Novel Protein-Ligand Binding 3D Matrix

Hydrogel materials have good biomimetic properties and high potential for biomedical and bioanalytical applications. In this work, a hydrogel of serum albumin crosslinked with poly-(ethylene glycol) was prepared and characterized for its water content, protein structure and stability. The ability of the hydrogel to bind small molecule ligands with different hydrophobicity was evaluated using a homologous series of amphiphiles (NBD-Cn, n = 4, 6 and 8) and the calculated binding affinities were similar to that of free protein in solution. Overall, the results indicate this type of hydrogel system as a convenient tool for studying the binding of xenobiotics to tissue proteins.info:eu-repo/semantics/publishedVersio

Epidemiologia molecular de um surto de bacteriemia por Enterobacter cloacae e Enterobacter agglomerans ocorrido na região de Campinas, São Paulo, Brasil

A total of 73 isolates (57 Enterobacter cloacae and 16 Enterobacter agglomerans), recovered during an outbreak of bacteremia in the Campinas area, São Paulo, Brazil, were studied. Of these isolates, 61 were from parenteral nutrition solutions, 9 from blood cultures, 2 from a sealed bottle of parenteral nutrition solution, and one was of unknown origin. Of the 57 E. cloacae isolates, 54 were biotype 26, two were biotype 66 and one was non-typable. Of 39 E. cloacae isolates submitted to ribotyping, 87.2% showed the same banding pattern after cleavage with EcoRI and BamHI. No important differences were observed in the antimicrobial susceptibility patterns among E. cloacae isolates exhibiting the same biotype, serotype and ribotype. All E. agglomerans isolates, irrespective of their origin, showed same patterns when cleaved with EcoRI and BamHI. The results of this investigation suggest an intrinsic contamination of parenteral nutrition solutions and incriminate these products as a vehicle of infection in this outbreak.Foram estudadas um total de 73 cepas (57 de E. cloacae e 16 E. agglomerans), isoladas durante um surto de bacteriemia ocorrido na região de Campinas, S. Paulo. Entre estas cepas, 61 foram isoladas de solução de nutrição parenteral, 9 de sangue, 2 de bolsa fechada de solução de nutrição parenteral e uma era de origem desconhecida. Entre as 57 cepas de E. cloacae, a maioria das cepas foram do biotipo 26/sorotipo O3 (39 cepas) e do biotipo 26/OR (13). Entre as 39 cepas de E. cloacae ribotipadas, 87,2% apresentaram o mesmo padrão de bandas com EcoRI e BamHI. Cepas de E. cloacae pertencentes ao mesmo biotipo, sorotipo e ribotipo não apresentaram diferenças significativas em relação ao padrão de sensibilidade aos agentes antimicrobianos. Todas as cepas de E. agglomerans, independente da origem, pertenciam ao mesmo ribotipo após a clivagem com EcoRI e BamHI. Os resultados obtidos sugerem uma contaminação intrínseca das soluções de nutrição parenteral, incriminando-as como o veículo de transmissão dos agentes etiológicos do surto

DIBMA nanodiscs keep α-synuclein folded

α-Synuclein (αsyn) is a cytosolic intrinsically disordered protein (IDP) known to fold into an α-helical structure when binding to membrane lipids, decreasing protein aggregation. Model membrane enable elucidation of factors critically affecting protein folding/aggregation, mostly using either small unilamellar vesicles (SUVs) or nanodiscs surrounded by membrane scaffold proteins (MSPs). Yet SUVs are mechanically strained, while MSP nanodiscs are expensive. To test the impact of lipid particle size on α-syn structuring, while overcoming the limitations associated with the lipid particles used so far, we compared the effects of large unilamellar vesicles (LUVs) and lipid-bilayer nanodiscs encapsulated by diisobutylene/maleic acid copolymer (DIBMA) on αsyn secondary-structure formation, using human-, elephant- and whale -αsyn. Our results confirm that negatively charged lipids induce αsyn folding in h-αsyn and e-αsyn but not in w-αsyn. When a mixture of zwitterionic and negatively charged lipids was used, no increase in the secondary structure was detected at 45 °C. Further, our results show that DIBMA/lipid particles (DIBMALPs) are highly suitable nanoscale membrane mimics for studying αsyn secondary-structure formation and aggregation, as folding was essentially independent of the lipid/protein ratio, in contrast with what we observed for LUVs having the same lipid compositions. This study reveals a new and promising application of polymer-encapsulated lipid-bilayer nanodiscs, due to their excellent efficiency in structuring disordered proteins such as αsyn into nontoxic α-helical structures. This will contribute to the unravelling and modelling aspects concerning protein-lipid interactions and α-helix formation by αsyn, paramount to the proposal of new methods to avoid protein aggregation and disease.info:eu-repo/semantics/publishedVersio

Nutrient‐efficient catfish‐based aquaponics for producing lamb's lettuce at two light intensities

ACKNOWLEDGMENTS We acknowledge funding provided by FCT/MCTES (PIDDAC): LA/P/0045/2020 (ALiCE), UIDB/50020/2020 & UIDP/50020/2020 (LSRE-LCM), UIDB/00313/2020 & UIDP/00313/2020 (CQC-IMS) and Rede Nacional de Ressonância Magnética Nuclear (RNRMN, UC-NMR).BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 ∼mol m−2 s −1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.info:eu-repo/semantics/publishedVersio

Nutritive Value and Bioactivities of a Halophyte Edible Plant: Crithmum maritimum L. (Sea Fennel)

Research funded by FEDER/COMPETE and Fundação para a Ciência e Tecnologia (FCT) via grants UIDB/00313/2020 and UIDP/00313/2020 to CQC, LA/P/0045/2020 to ALiCE, UIDB/50020/2020 and UIDP/50020/2020 to LSRE-LCM, and UIDB/MAR/04292/2020 to MARE, and to the Integrated Programme of SR&TD “Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate” (Centro-01-0145-FEDER-000018) and to Rede Nacional de Ressonância Magnética Nuclear (RNRMN, UC-NMR).Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel’s salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.info:eu-repo/semantics/publishedVersio

Crithmum maritimum L. (Sea Fennel)

Funding Information: Research funded by FEDER/COMPETE and Fundação para a Ciência e Tecnologia (FCT) via grants UIDB/00313/2020 and UIDP/00313/2020 to CQC, LA/P/0045/2020 to ALiCE, UIDB/50020/2020 and UIDP/50020/2020 to LSRE-LCM, and UIDB/MAR/04292/2020 to MARE, and to the Integrated Programme of SR&TD “Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate” (Centro-01-0145-FEDER-000018) and to Rede Nacional de Ressonância Magnética Nuclear (RNRMN, UC-NMR). Publisher Copyright: © 2024 by the authors.Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel’s salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.publishersversionpublishe