The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, including primarily neurodegenerative diseases. Such disorders are characterized by ...misfolded proteins that lose their normal physiological roles and acquire toxicity. Recent findings suggest that proteostasis network impairment may be one of the causes leading to the accumulation and spread of amyloids. These observations are certainly contributing to a new focus in anti‐amyloid drug design, whose efforts are so far being centered on single‐target approaches aimed at inhibiting amyloid aggregation. Chaperones, known to maintain proteostasis, hence represent interesting targets for the development of novel therapeutics owing to their potential protective role against protein misfolding diseases. In this minireview, research on nanoparticles that can either emulate or help molecular chaperones in recognizing and/or correcting protein misfolding is discussed. The nascent concept of “nanochaperone” may indeed set future directions towards the development of cost‐effective, disease‐modifying drugs to treat several currently fatal disorders.
Nanoparticles with chaperone‐like activity may be considered as potential therapeutic agents to treat conformational diseases. This Minireview aims at emphasising the essential features required by nanomaterials to deal with toxic protein misfolding and accumulation.
The aim of this research is to present a successful flipped classroom proposal in higher education to better understand its influence in terms of knowledge, skills and engagement. The reason why we ...focus on these three dimensions is because of their core roles in the international learning conceptual frameworks presented above to increase the employability of Generation Z students in the digital society of the 21st century. In doing so, first, we first develop a measurement scale (4D_FLIPPED) to explore the degree of flipped classroom presence in our higher education learning experience. Then, we present a structural equation model to analyze the causal relationships of knowledge, skills, and engagement with students' satisfaction. The empirical results point out that there are four fundamental dimensions that should be present in the flipped classroom to be successful in the 21st century with Generation Z. This study also confirms that the flipped classroom has positive effects on students’ knowledge, skills, and engagement. Our research provides useful recommendations and insights for academia.
•A flipped classroom measurement scale (4D_FLIPPED) is proposed and tested in higher education.•A partial least squares (PLS) approach for structural equation modeling (SEM) is employed.•Empirical evidence is provided about the relationships among knowledge, skills, engagement, and students' satisfaction.•Useful recommendations and insights are provided for academia.
In spite of its large availability in natural or shale gas deposits, the use of methane in the chemical industry as feedstock from a synthetic point of view yet constitutes a challenge in modern ...chemistry. Only the production of the so-called
syngas
, a mixture of CO and H
2
derived from the complete cleavage of the methane molecule, operates at the industrial level. The relevance of methane in the current industry, mainly toward methanol production, is described in this Tutorial. The
methanol economy
has been already proposed as an alternative to current fuel sources. Methanol synthesis directly from methane would imply the activation of the latter. Toward this end, the different methodologies reported to activate methane with transition metal complexes as well as the few examples of the catalytic functionalization of methane are presented.
The activation and catalytic functionalization of methane are reviewed showing that this area requires further and urgent development in the incoming years.
Since their first synthesis back in the early 20th century, 1,2,4-triazolo1,5- apyrimidines have aroused increasing interest in very diverse areas ranging from chemotherapy to agriculture or even ...photography. Their similarity to purines confers a potential bioactivity and this feature has been wisely exploited for therapeutic use, including antifungal, antipyretic, analgesic, antiinflammatory, antitumoral and antiparasitic properties. In this review, we focus on the compounds that these nitrogen heterocycles form with metal ions and their antiparasitic activity and therapeutic potential against two neglected diseases of tropical prevalence, leishmaniasis and Chagas disease.
The photoactivation of potential anticancer metal complexes is a hot topic of current research as it may lead to the development of more selective drugs. Photoactivated chemotherapy (PACT) with ...coordination compounds is usually based on a (photo)chemical reaction taking place at the metal center. Herein, a new strategy is exploited that consists of “photomodifying” a ligand coordinated to metal ions. Platinum(II) complexes from photoswitchable 1,2‐dithienylethene‐containing ligands have been prepared, which exhibit two interconvertible photoisomeric forms that present distinct DNA‐interacting properties and cytotoxic behaviors.
Toxic switch: The photoswitchable open and closed forms of 1,2‐dithienylethene‐based platinum(II) compounds exhibit distinct DNA‐interacting and cytotoxic properties, which may lead to a new class of potential photoactivatable anticancer agents.
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely ...evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.
Competitive Cu(II)-binding studies have been carried out between five decapeptides (both acyclic and cyclic), namely C-Asp, C-Asn, O-Asp, O DPro -Asp, and O-Asn, and the Aβ(1–16) and Aβ(1–40) ...fragments. Conformational constraints in such peptidic scaffolds affect their copper-binding affinity, which can be tuned. In the present study, the ability of these peptides to compete with Aβ has been assessed in vitro, with the objective to examine whether such soft chelating agents may be used to lessen the deleterious interaction of Cu(II) with Aβ. Fluorescence spectroscopy, electron paramagnetic resonance, and mass spectrometry data show that the more constrained peptide, i.e., cyclic C-Asp, which displays a Cu(II)-binding affinity comparable to that of Aβ, is the only potential metal-protein attenuating compound (MPAC) candidate. In vitro aggregation studies with Aβ(1–40) reveal that C-Asp can hamper the formation of copper-stabilized oligomeric Aβ species, through capturing the metal ion prior to its interaction with monomeric Aβ. The present study shows that (cyclic) peptides, preorganized for Cu(II) binding, may be applied for the development of potential copper-Aβ attenuating compounds.
Objective
The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using ...data‐driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome.
Methods
We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models—a logistic regression, a multilayer perceptron, and an XGBoost model—to predict 1‐year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance.
Results
Our logistic regression achieved an accuracy of 72% (95% confidence interval CI = 68%–75%, area under the curve AUC = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%–74%, AUCMLP = .70; 95% CIXGBoost own = 68%–75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%–67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data‐driven feature selection.
Significance
We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.
Dimensioning the Term Carbenoid Caballero, Ana; Pérez, Pedro J.
Chemistry : a European journal,
October 17, 2017, Letnik:
23, Številka:
58
Journal Article
Recenzirano
Odprti dostop
The current use of the term carbenoid is discussed, particularly in the context of carbene transfer reactions from diazo compounds, in which intermediates of type LnM=CR1R2, or one of its resonance ...forms, are tagged which such a name. We discuss this issue, on the basis of the data evidencing the metal‐carbene nature of those intermediates, as well as the existence of carbenoids of type (N2)(M)CR1R2 en route to the formation to LnM=CR1R2′ from diazo reagents. We propose the exclusive use of the carbenoid term to species of type (X)(M)CR1R2 with a tetrasubstituted carbon center that upon loss of X afford an effective carbene transfer process.
The truth about carbenoids: The term carbenoid is employed in the current literature to define either a species bearing a tetrasubstituted carbon from which a metal–carbene species can be formed or the latter complex itself, particularly in the context of a carbene transfer reaction from diazo compounds. The exclusive use of this term referring to the former species is proposed.
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