Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers

Alzheimer's Disease (AD) and Parkinson's Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble beta-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. At present, there is no effective drug available, and patients are left with symptomatic and inconclusive therapies. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. In this article, we will review and put into perspective results from ex vivo and in vivo studies performed on compounds specifically interacting with such early species. Following a general overview on the three different amyloid proteins leading to insoluble beta-sheet-rich amyloid deposits (amyloid beta(1-42) peptide, Tau, and alpha-synuclein), a list of the advantages and disadvantages of the approaches employed to date is discussed, with particular attention paid to the translation of fluorescence imaging into clinical applications. Furthermore, we also discuss how the progress achieved in detecting the amyloids of one neurodegenerative disease could be leveraged for research into another amyloidosis. As evidenced by a critical analysis of the state of the art, substantial work still needs to be conducted. Indeed, the early diagnosis of neurodegenerative diseases is a priority, and we believe that this review could be a useful tool for better investigating this field

Insights into the Structural Conformations of the Tau Protein in Different Aggregation Status

Tau is a protein characterized by large structural portions displaying extended conformational changes. Unfortunately, the accumulation of this protein into toxic aggregates in neuronal cells leads to a number of severe pathologies, collectively named tauopathies. In the last decade, significant research advancements were achieved, including a better understanding of Tau structures and their implication in different tauopathies. Interestingly, Tau is characterized by a high structural variability depending on the type of disease, the crystallization conditions, and the formation of pathologic aggregates obtained from in vitro versus ex vivo samples. In this review, we reported an up-to-date and comprehensive overview of Tau structures reported in the Protein Data Bank, with a special focus on discussing the connections between structural features, different tauopathies, different crystallization conditions, and the use of in vitro or ex vivo samples. The information reported in this article highlights very interesting links between all these aspects, which we believe may be of particular relevance for a more informed structure-based design of compounds able to modulate Tau aggregation

Kinetic and thermodynamic behavior of co-pyrolysis of olive pomace and thermoplastic waste via thermogravimetric analysis

This work represents the first attempt to analyze kinetics, thermodynamics and reaction mechanism of olive pomace (OP) and waste plastic materials (PM) co-pyrolysis. Among PM, polypropylene (PP), polystyrene (PS), high density polypropylene (HDPE), polyvinyl chloride (PVC) and poly (ethylene terephthalate) glycol (PETG) were selected. Non-isothermal TG experiments were carried out under inert conditions at four heating rates, namely 5, 10, 20 and 40 °C/min. The kinetic triplet for raw materials and their blends was determined using Starink, Kissinger-Akahira-Sunose and Ozawa-Flynn-Wall iso-conversional models. Pyrolysis mechanism reactions were explained by diverse models, depending on thermal degradation progress. Results shown that co-pyrolysis followed a complex multi-step reaction mechanism. A synergistic effect was detected during co-pyrolysis of OP/PM mixtures. The addition of 50 % (w/w) OP biomass to PM waste decreased the energy of activation (Ea) from 50 to 25 % for all blends, except for PVC/OP. Thermodynamic analysis reveals that adding OP generally reduces the energy barrier (ΔH), except for PS-OP, and improves energy efficiency (ΔG) by facilitating radical formation and molecular chain cleavage. As a conclusion, this study may open up new avenues for waste valorization and resource recovery. Thus, it may contribute to the transition towards a circular and sustainable economy, through zero waste goal

Kinetic and thermodynamic behavior of co-pyrolysis of olive pomace and thermoplastic waste via thermogravimetric analysis

This work represents the first attempt to analyze kinetics, thermodynamics and reaction mechanism of olive pomace (OP) and waste plastic materials (PM) co-pyrolysis. Among PM, polypropylene (PP), polystyrene (PS), high density polypropylene (HDPE), polyvinyl chloride (PVC) and poly (ethylene terephthalate) glycol (PETG) were selected. Non-isothermal TG experiments were carried out under inert conditions at four heating rates, namely 5, 10, 20 and 40 °C/min. The kinetic triplet for raw materials and their blends was determined using Starink, Kissinger-Akahira-Sunose and Ozawa-Flynn-Wall iso-conversional models. Pyrolysis mechanism reactions were explained by diverse models, depending on thermal degradation progress. Results shown that co-pyrolysis followed a complex multi-step reaction mechanism. A synergistic effect was detected during co-pyrolysis of OP/PM mixtures. The addition of 50 % (w/w) OP biomass to PM waste decreased the energy of activation (Ea) from 50 to 25 % for all blends, except for PVC/OP. Thermodynamic analysis reveals that adding OP generally reduces the energy barrier (ΔH), except for PS-OP, and improves energy efficiency (ΔG) by facilitating radical formation and molecular chain cleavage. As a conclusion, this study may open up new avenues for waste valorization and resource recovery. Thus, it may contribute to the transition towards a circular and sustainable economy, through zero waste goal

Quantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction

Tauopathies such as Alzheimer’s disease are characterized by aggregation and increased phosphorylation of the microtubule-associated protein tau. Tau’s pathological changes are closely linked to neurodegeneration, making tau a prime candidate for intervention. We developed an approach to monitor pathological changes of aggregation-prone human tau in living neurons. We identified 2-phenyloxazole (PHOX) derivatives as putative polypharmacological small molecules that interact with tau and modulate tau kinases. We found that PHOX15 inhibits tau aggregation, restores tau’s physiological microtubule interaction, and reduces tau phosphorylation at disease-relevant sites. Molecular dynamics simulations highlight cryptic channel-like pockets crossing tau protofilaments and suggest that PHOX15 binding reduces the protofilament’s ability to adopt a PHF-like conformation by modifying a key glycine triad. Our data demonstrate that live-cell imaging of a tauopathy model enables screening of compounds that modulate tau-microtubule interaction and allows identification of a promising polypharmacological drug candidate that simultaneously inhibits tau aggregation and reduces tau phosphorylation

A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy

We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km 2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting

Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering

The need to develop and improve sustainable energy resources is of eminent importance due to the finite nature of our fossil fuels. This review paper deals with a third generation renewable energy resource which does not compete with our food resources, cyanobacteria. We discuss the current state of the art in developing different types of bioenergy (ethanol, biodiesel, hydrogen, etc.) from cyanobacteria. The major important biochemical pathways in cyanobacteria are highlighted, and the possibility to influence these pathways to improve the production of specific types of energy forms the major part of this review

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe