At the beginning of the 21st century, the therapeutic management of neurodegenerative disorders remains a major biomedical challenge, particularly given the worldwide ageing of the population over ...the past 50 years that is expected to continue in the forthcoming years. This review will focus on the promise of cannabinoid‐based therapies to address this challenge. This promise is based on the broad neuroprotective profile of cannabinoids, which may cooperate to combat excitotoxicity, oxidative stress, glia‐driven inflammation and protein aggregation. Such effects may be produced by the activity of cannabinoids through their canonical targets (e.g. cannabinoid receptors and endocannabinoid enzymes) and also via non‐canonical elements and activities in distinct cell types critical for cell survival or neuronal replacement (e.g. neurons, glia and neural precursor cells). Ultimately, the therapeutic events driven by endocannabinoid signalling reflect the activity of an endogenous system that regulates the preservation, rescue, repair and replacement of neurons and glia.
Linked Articles
This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
The methanol-to-aromatics (MTA) process is regarded as a promising route to produce aromatic commodities through non-petroleum carbon resources, such as biomass, waste, coal, natural gas, and CO2. In ...contrast with the industrially implemented methanol-to-olefin (MTO) process, most MTA studies are still in the laboratory-scale stage. Recently, a few demonstration plants of MTA have been successfully launched, indicating the importance and the gradual industrial maturity of this technology. However, there are still many fundamental questions and technological challenges that must be addressed. In this Review, we summarize the recent advances in mechanistic understanding on the reaction and catalyst deactivation during MTA, elaborate the available strategies to improve the catalytic performance, and correlate MTA studies with other important catalytic aromatization processes. With this knowledge in hand, we share our views on future research directions in this field.
A warped scalar portal to fermionic dark matter Carmona, Adrian; Castellano Ruiz, Javier; Neubert, Matthias
The European physical journal. C, Particles and fields,
2021/1, Letnik:
81, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We argue that extensions of the SM with a warped extra dimension, together with a new
Z
2
-odd scalar singlet, provide a natural explanation not only for the hierarchy problem but also for the nature ...of fermion bulk masses and the observed dark matter relic abundance. In particular, the Kaluza-Klein excitations of the new scalar particle, which is required to naturally obtain fermion bulk masses through Yukawa-like interactions, can be the leading portal to any fermion propagating into the bulk of the extra dimension and playing the role of dark matter. Moreover, such scalar excitations will necessarily mix with the Higgs boson, leading to modifications of the Higgs couplings and branching ratios, and allowing the Higgs to mediate the coannihilation of the fermionic dark matter. We study these effects and explore the viability of fermionic dark matter in the presence of these new heavy scalar mediators both in the usual freeze-out scenario and in the case where the freeze-out happens during an early period of matter domination.
We present a detailed theoretical analysis of the reaction mechanism of proteolysis catalyzed by the main protease of SARS-CoV-2. Using multiscale simulation methods, we have characterized the ...interactions established by a peptidic substrate in the active site, and then we have explored the free energy landscape associated with the acylation and deacylation steps of the proteolysis reaction, characterizing the transition states of the process. Our mechanistic proposals can explain most of the experimental observations made on the highly similar ortholog protease of SARS-CoV. We point to some key interactions that may facilitate the acylation process and thus can be crucial in the design of more specific and efficient inhibitors of the main protease activity. In particular, from our results, the P1′ residue can be a key factor to improve the thermodynamics and kinetics of the inhibition process.
The ongoing crisis in Europe has dramatic impact on the life in many Southern European cities: Unemployment, social deprivation, poverty, political instability, severe cuts in the welfare state ...budgets and a wide spread feeling of despair have eroded much of the social foundation of the cities. In this book, contributors from Spain, Greece, Portugal and Italy provide an insight into the complex interference between the different aspects of the crisis. They show that the recent urban crisis is not purely a result of the budgetary problems of the nation state (»austerity urbanism«) but needs to be seen as multiple contestations. The Crisis of the City is therefore understood as a result of a changing nation state, cultural diversity, challenged urban planning and politics and a globalized economy.
There is evidence that cannabinoid‐based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial ...in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD). These benefits not only include the alleviation of specific motor symptoms e.g. choreic movements with cannabinoid receptor type 1 (CB1)/transient receptor potential vanilloid type 1 agonists in HD; bradykinesia with CB1 antagonists and tremor with CB1 agonists in PD, but also the delay of disease progression due to the neuroprotective properties demonstrated for cannabinoids (e.g. CB1 agonists reduce excitotoxicity; CB2 agonists limit the toxicity of reactive microglia; and antioxidant cannabinoids attenuate oxidative damage). In addition, extensive biochemical, anatomical, physiological and pharmacological studies have demonstrated that: (i) the different elements of the cannabinoid system are abundant in basal ganglia structures and they are affected by these disorders; (ii) the cannabinoid system plays a prominent role in basal ganglia function by modulating the neurotransmitters that operate in the basal ganglia circuits, both in healthy and pathological conditions; and (iii) the activation and/or inhibition of the cannabinoid system is associated with important motor responses that are maintained and even enhanced in conditions of malfunctioning and/or degeneration. In this article we will review the available data regarding the relationship between the cannabinoid system and basal ganglia activity, both in healthy and pathological conditions and will also try to identify future lines of research expected to increase current knowledge about the potential therapeutic benefits of targeting this system in PD, HD and other basal ganglia disorders.
Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very ...challenging. Here, we tackle this question by comparing an enzyme with its heavy (¹⁵N, ¹³C, ²H substituted) counterpart, providing a subtle probe of dynamics. The crucial hydride transfer step of the reaction (the chemical step) occurs more slowly in the heavy enzyme. A combination of experimental results, quantum mechanics/molecular mechanics simulations, and theoretical analyses identify the origins of the observed differences in reactivity. The generally slightly slower reaction in the heavy enzyme reflects differences in environmental coupling to the hydride transfer step. Importantly, the barrier and contribution of quantum tunneling are not affected, indicating no significant role for “promoting motions” in driving tunneling or modulating the barrier. The chemical step is slower in the heavy enzyme because protein motions coupled to the reaction coordinate are slower. The fact that the heavy enzyme is only slightly less active than its light counterpart shows that protein dynamics have a small, but measurable, effect on the chemical reaction rate.
Peer assessment is a popular research topic as it takes place in multiple educational settings around the globe. Due to its nature, a number of intrapersonal and interpersonal factors are involved. ...Empirical research on these factors has been increasing and our aim was to systematically review them to extract conclusions about the relationships between peer assessment and intrapersonal and interpersonal factors. Using different search strategies, we reviewed 69 articles. We investigated: (1) the characteristics of the included studies, (2) the trends in the bidirectional relationships of intrapersonal ←→ peer assessment and interpersonal ←→ peer assessment, (3) the empirical findings in the relationships between intrapersonal factors and peer assessment, and (4) the empirical findings in the relationships between interpersonal factors and peer assessment. We identified six intrapersonal factors: motivation, self-efficacy, emotions, trust in the self as assessor, fairness, and comfort; and five interpersonal factors: social connections, trust in the other as assessor, psychological safety, value diversity/congruence, and interdependence. The results showed clear directions for some of those factors and preliminary in some of the others. This review offers directions to improve the quality of peer assessment research and explores the role of bidirectionality for future research, including an instrument to report the characteristics of future peer assessment studies to facilitate better reports and research designs.
The growing number of peer assessment studies in the last decades created diverse design options for researchers and teachers to implement peer assessment. However, it is still unknown if there are ...more commonly used peer assessment formats and design elements that could be considered when designing peer assessment activities in educational contexts. This systematic review aims to determine the diversity of peer assessment designs and practices in research studies. A literature search was performed in the electronic databases PsycINFO, PsycARTICLES, Web of Science Core Collection, Medline, ERIC, Academic Search Premier, and EconLit. Using data from 449 research studies (derived from 424 peer-reviewed articles), design differences were investigated for subject domains, assessment purposes, objects, outcomes, and moderators/mediators. Arts and humanities was the most frequent subject domain in the reviewed studies, and two-third of the studies had a formative purpose of assessment. The most used object of assessment was written assessment, and beliefs and perceptions were the most investigated outcomes. Gender topped the list of the investigated moderators/mediators of peer assessment. Latent class analysis of 27 peer assessment design elements revealed a five-class solution reflecting latent patterns that best describe the variability in peer assessment designs (i.e. prototypical peer assessment designs). Only ten design elements significantly contributed to these patterns with an associated effect size
R
2
ranging from .204 to .880, indicating that peer assessment designs in research studies are not as diverse as they theoretically can be.
ABSTRACT
The consumption of sugar-free foods is growing because of their low-calorie content and the health concerns about products with high sugar content. Sweeteners that are frequently several ...hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. Although nonnutritive sweeteners (NNSs) are considered safe and well tolerated, their effects on glucose intolerance, the activation of sweet taste receptors, and alterations to the composition of the intestinal microbiota are controversial. This review critically discusses the evidence supporting the effects of NNSs, both synthetic sweeteners (acesulfame K, aspartame, cyclamate, saccharin, neotame, advantame, and sucralose) and natural sweeteners (NSs; thaumatin, steviol glucosides, monellin, neohesperidin dihydrochalcone, and glycyrrhizin) and nutritive sweeteners (polyols or sugar alcohols) on the composition of microbiota in the human gut. So far, only saccharin and sucralose (NNSs) and stevia (NS) change the composition of the gut microbiota. By definition, a prebiotic is a nondigestible food ingredient, but some polyols can be absorbed, at least partially, in the small intestine by passive diffusion: however, a number of them, such as isomaltose, maltitol, lactitol, and xylitol, can reach the large bowel and increase the numbers of bifidobacteria in humans. Further research on the effects of sweeteners on the composition of the human gut microbiome is necessary.
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