Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review

The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs

Monitoring the reduction in shrinkage cracking of mortars containing superabsorbent polymers

Ultra-high performance concrete (UHPC) is characterized by a low water-to-cement ratio, leading to improved durability and mechanical properties. However, the risk for autogenous shrinkage and cracking due to restrained shrinkage increases, which may affect the durability of UHPC as cracks form pathways for ingress of aggressive liquids and gases. These negative features can be prevented by the use of superabsorbent polymers (SAPs) in the mixture. SAPs reduce autogenous shrinkage by means of internal curing: they will absorb water during the hydration process and release it again to the cementitious matrix when water shortage arises. In this way, hydration can continue and shrinkage is diminished

The importance of understanding function and evolution

Ocklenburg et al. (2020, Laterality 2020: Entering the next decade. Laterality) provided the field of laterality research with a stimulating research perspective for the coming decade, based on the current state of the art in both animal and human laterality research. Although this is paper takes many different approaches of laterality into account, we emphasize that the eco-evolutionary approach needs more attention. This concerns the question why organisms are lateralized in the first place, in other words, how does lateralization enhance the Darwinian fitness of the individual. We argue that laterality can be distinguished along four dimensions, and that each of them requires different ultimate explanations. Studying these functional and evolutionary explanations requires the development of ecologically relevant tests, adapted to the species at hand. It also requires experimental manipulation of laterality, testing the effect in (semi)-natural conditions on fitness parameters. Tools for such manipulation of laterality urgently require a better understanding of the developmental plasticity of lateralization, extending the field of evo-devo to that of eco-evo-devo. We also warn against seeing the minority in the distribution of direction or strength of lateralization as being a pathology as such minorities in biology can often be explained as adaptations by natural frequency dependent selection

Is imitational learning a driving factor for the population bias in human hand preference?

Lateral preference is a widespread organizational principle in human and nonhuman animals. In humans, the most apparent lateralized trait (handedness) is unique in the animal kingdom because of a very pronounced bias towards right-handedness on a population level. In this study, based on previous experiments, we test the hypothesis that this bias was-among other factors-shaped by evolution through the facilitation of social learning. We exposed 134 subjects to footage of right- or left-handed knot making and analyzed whether concordant handedness between instructor and student facilitated quicker and more successful imitation. We used a set of nautical knots of different difficulty levels in order to test whether the potential effect of concordance became stronger with increasing knot difficulty. For all three performance measures (time until correct completion, number of attempts needed and correct imitation), we found hand congruency and difficulty level to be significant predictors but not the interaction of the two. We conclude that concordance of handedness between teacher and student of a motor skill enhances the speed and accuracy of imitation, which may have been a beneficial trait for selection to act upon, thereby shaping the human population bias in handedness

Testing the Darwinian function of lateralization:Does separation of workload between brain hemispheres increase cognitive performance?

Brain lateralization is a fundamental aspect of the organization of brain and behavior in the animal kingdom, begging the question about its Darwinian function. We tested the possibility that lateralization enhances cognitive performance in single- and dual-tasks. Previous studies reported mixed results on this topic and only a handful of studies have measured functional brain lateralization and performance independently and simultaneously. We therefore examined a possible positive effect of the strength and direction of lateralization on two demanding cognitive tasks: A visuospatial task (mental rotation MR), and a language task (word generation WG), executed either as a singletask or as dual-task. Participants (n = 72) performed these tasks while their single-task brain lateralization was assessed with functional Transcranial Doppler for both tasks. From these measurements we determined strength and direction of lateralization for both tasks and the individual pattern of lateralization (contralateral or ipsilateral) was derived. These factors, along with sex, were used in a GLM analysis to determine if they predicted the respective performance measure of the tasks. We found that for MR there was a significant medium effect of direction of lateralization on performance with better performance in left-lateralized (atypical) participants (partial eta squared 0.061; p = .039). After correction for outliers, there was a significant effect for strength (p = .049). For the dual-task, there was a significant positive medium effect of strength of lateralization on performance (partial eta squared 0.062; p = .038, respectively) No other association between direction or strength in either tests were found. We conclude that there is no evidence for hemispheric crowding, and that strength of lateralization may be a factor that contributes to the evolutionary selection of functional brain lateralization. Pattern of lateralization does not, explaining the large inter-individual variation in these traits

Does hand skill asymmetry relate to creativity, developmental and health issues and aggression as markers of fitness?

A remarkable feature of human handedness at the population level is specialization of the hands, the right hand performing usually better than the left. This specialization might have an evolutionary advantage, because it provides the individual and population with a wider range of skill. We therefore investigated the relationships between hand skill asymmetry and potential markers of Darwinian fitness that have been hypothesized to explain the bias in hand preference: creativity, aggression and developmental and health problems. Over twenty thousand participants (56% left-handers) completed an online survey, including a finger-tapping task to measure hand skill asymmetry. Left-skilled individuals were overall more aggressive than right-skilled individuals and rated themselves as more artistically creative. However, when assessed with a questionnaire, they were less creative on problem solving and equally artistically creative compared to right-skilled individuals, who reported more health problems. Conclusion: we found some evidence for current selection on the direction of lateralization of hand skill although the effect sizes were rather low. Strength of lateralization of hand skill showed only a few associations with fitness proxies. We suggest that Darwinian selection on hand preference (Zickert, Feen, van der, Geuze, & Groothuis, 2018. Fitness costs and benefits associated with hand preference in humans: A large internet study in a Dutch sample. Evolution and Human Behavior, 39, 235-248) and hand skill asymmetry (present study) may be attenuated in modern society

Tube shape alterations for improved concrete pouring survivability in vascular self-healing concrete

The upscaling of self-healing mechanisms for concrete from simple laboratory experiments to full-size industrial applications remains a huge challenge. In the present work, the potential for upscaling of vascular self-healing is investigated. The vanes of the vascular system, should on one hand be strong enough to survive the rather aggressive concrete production conditions, i.e. casting and pouring, while on the other hand they should be brittle in order to break when a crack in the hardened concrete surpasses them in the hardened concrete. Until now, the search for suitable materials received most attention and often the influence of the geometry was neglected. This work the shape is altered in order to investigate its influence on the survivability of the system under real production conditions. For vascular systems, the vanes should be able to resist the high forces when concrete is poured onto it. A comparison between different shapes is made, i.e. circular, square, droplet and ellipsoidal (i.e. rugby-ball) shaped cross section. From this study it can be seen that the shape is a parameter that could help to survive the pouring process

Experimental techniques synergy towards the design of a sensing tool for autonomously healed concrete

The first-generation of autonomously healed concrete elements is under construction: beams (SIM-SECEMIN project, Flanders Belgium), one-way flat slabs (MeMC, VUB, Belgium) and wall panels (Materials4Life project, UK) are designed with the embedment of encapsulated repair agent. In the presence of cracks, capsules rupture releasing the agent that fills the crack void. The released agent seals and mechanically restores the crack discontinuity. This automatic process can be repeatable using vascular networks that carry the agent and release it at different locations into concrete. The innovative design is built up following several series of laboratory-scale beam tests configured over the last decade. This paper discusses the application of numerous experimental techniques that assess the mechanical performance of autonomously healed concrete: Acoustic Emission, Ultrasound Pulse Velocity, Optical Microscopy, Digital Image Correlation, Capillary Water Absorption, Computed Tomography. The study focuses on the performance and efficiency of each method on laboratory and real-scale tests. The techniques with the most promising output are selected and combined in order to design a sensing tool that evaluates healing on real applications

Elastic wave monitoring of cementitious mixtures including internal curing mechanisms

The mitigation of autogenous shrinkage in cementitious materials by internal curing has been widely studied. By the inclusion of water reservoirs, in form of saturated lightweight aggregates or superabsorbent polymers, additional water is provided to the hydrating matrix. The onset of water release is of high importance and determines the efficiency of the internal curing mechanism. However, the monitoring of it poses problems as it is a process that takes place in the microstructure. Using acoustic emission (AE) sensors, the internal curing process is monitored, revealing its initiation and intensity, as well as the duration. In addition, AE is able to capture the water evaporation from saturated specimens. By ultrasonic testing, differences in the hydration kinetics are observed imposed by the different methods of internal curing. The results presented in this paper show the sensitivity of combined AE and ultrasound experiments to various fundamental mechanisms taking place inside cementitious materials and demonstrate the ability of acoustic emission to evaluate internal curing in a non-destructive and easily implementable way