Alzheimer's disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery ...of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.
The future of hotels Lub, Xander D; Rijnders, René; Caceres, Laura Niño ...
Journal of vacation marketing,
07/2016, Letnik:
22, Številka:
3
Journal Article
Recenzirano
This article explores the use of design thinking as a method to develop scenario for the future of hotels. Using a Dutch case study, this article shows how a new concept for hotels – the Lifestyle ...Hub – was created using design thinking as methodology. The Lifestyle Hub concept provides ingredients to hotel owners as well as public policymakers to help understand how future guests may expect to make use of individually tailored hospitable facilities in destinations around the world. Moreover, design thinking allows researchers and businesses to generate highly differentiated customer-centred, experience-based business concepts, thus adding to the toolkit of futures researchers. We conclude that design thinking provides new insights for hospitality and tourism and presents a valuable alternative to current future scenarios approaches.
Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tangles are prime features of Alzheimer's disease (AD). The pathology of AD is very complex and still not fully ...understood, since different neural cell types are involved in the disease. Although neuronal function is clearly deteriorated in AD patients, recently, an increasing number of evidences have pointed towards glial cell dysfunction as one of the main causative phenomena implicated in AD pathogenesis. The complex disease pathology together with the lack of reliable disease models have precluded the development of effective therapies able to counteract disease progression. The discovery and implementation of human pluripotent stem cell technology represents an important opportunity in this field, as this system allows the generation of patient-derived cells to be used for disease modeling and therapeutic target identification and as a platform to be employed in drug discovery programs. In this review, we discuss the current studies using human pluripotent stem cells focused on AD, providing convincing evidences that this system is an excellent opportunity to advance in the comprehension of AD pathology, which will be translated to the development of the still missing effective therapies.
The accumulation of toxic metals and metalloids, such as cadmium (Cd), mercury (Hg), or arsenic (As), as a consequence of various anthropogenic activities, poses a serious threat to the environment ...and human health. The ability of plants to take up mineral nutrients from the soil can be exploited to develop phytoremediation technologies able to alleviate the negative impact of toxic elements in terrestrial ecosystems. However, we must select plant species or populations capable of tolerating exposure to hazardous elements. The tolerance of plant cells to toxic elements is highly dependent on glutathione (GSH) metabolism. GSH is a biothiol tripeptide that plays a fundamental dual role: first, as an antioxidant to mitigate the redox imbalance caused by toxic metal(loid) accumulation, and second as a precursor of phytochelatins (PCs), ligand peptides that limit the free ion cellular concentration of those pollutants. The sulphur assimilation pathway, synthesis of GSH, and production of PCs are tightly regulated in order to alleviate the phytotoxicity of different hazardous elements, which might induce specific stress signatures. This review provides an update on mechanisms of tolerance that depend on biothiols in plant cells exposed to toxic elements, with a particular emphasis on the Hg-triggered responses, and considering the contribution of hormones to their regulation.
Cadmium (Cd) and mercury (Hg) are ubiquitous soil pollutants that promote the accumulation of reactive oxygen species, causing oxidative stress. Tolerance depends on signalling processes that ...activate different defence barriers, such as accumulation of small heat sock proteins (sHSPs), activation of antioxidant enzymes, and the synthesis of phytochelatins (PCs) from the fundamental antioxidant peptide glutathione (GSH), which is probably modulated by ethylene. We studied the early responses of alfalfa seedlings after short exposure (3, 6, and 24 h) to moderate to severe concentration of Cd and Hg (ranging from 3 to 30 μM), to characterize in detail several oxidative stress parameters and biothiol (i.e., GSH and PCs) accumulation, in combination with the ethylene signalling blocker 1-methylcyclopropene (1-MCP). Most changes occurred in roots of alfalfa, with strong induction of cellular oxidative stress, H
O
generation, and a quick accumulation of sHSPs 17.6 and 17.7. Mercury caused the specific inhibition of glutathione reductase activity, while both metals led to the accumulation of PCs. These responses were attenuated in seedlings incubated with 1-MCP. Interestingly, 1-MCP also decreased the amount of PCs and homophytochelatins generated under metal stress, implying that the overall early response to metals was controlled at least partially by ethylene.
Cyclic alternanting pattern (CAP) has been considered a marker of sleep instability in children. The aim of this study was to evaluate the CAP in infants with laryngomalacia.
CAP were quantified in ...15 infants with laryngomalacia (mean age 167.2±97.21 days) and 10 controls (mean age of 158.5±116.2 days) using polysomnography.
The distribution of the A2 subtypes across NREM stages in infants with laryngomalacia showed a decrease, as well as in the mean duration of CAP sequences. The A3 CAP and arousals increased in infants with laryngomalacia. Our data showed a stronger correlation between the mean duration of A1 CAP and the age in healthy controls than in infants with laryngomalacia. In accordance to previous reports infants with laryngomalacia exhibited an increase in total awake time, apnea-hypopnea index, and a decrease in N3 stage compared to controls.
Our findings add to a growing body of literature of CAP as an indicator of brain maturation.
Several physiological parameters related to oxidative stress, which is a characteristic of plants exposed to toxic metals, were studied in 3-week-old alfalfa plants treated with cadmium (Cd) or ...mercury (Hg) at doses of 0, 3, 10 and 30
μM for 7
d. The concentrations of biothiols, glutathione (GSH), homoglutathione (hGSH) and phytochelatins (PCs) increased dramatically in metals-treated plants, in particular in the presence of Cd. This was accompanied by a remarkable up-regulation of γ-glutamyl cysteine synthetase gene, probably in response to the higher demand for GSH|hGSH needed for PC synthesis. The presence of metals enhanced lipid peroxidation in shoots, while chlorophyll content declined in a concentration dependent manner. Ascorbate peroxidase (APX) activity increased moderately in roots of Cd-exposed plants, and a new basic root peroxidase isoform was found in both Cd- and Hg-treated plants. Glutathione reductase (GR) activity was enhanced in shoots of plants exposed to Cd and Hg. However, this enzymatic activity showed a metal dependent response in roots, and was enhanced in Cd-treated plants but was severely inhibited in roots of plants treated with Hg. Inhibition of GR by Hg was confirmed
in vitro by incubating a commercially available GR and control shoot extracts with several doses of Hg and Cd. Ascorbate concentrations were elevated with treatments of 3
μM Hg, 10
μM Cd and 30
μM Cd, indicating that this compound is necessary for redox cellular homeostasis. The different responses observed with Cd and Hg treatments might be the basis for specific stress bioindicators.
One of the most widely used strategies for optimizing training tasks is to modify the number of players, the Game Situations. The aim of this study was to analyse the influence of the Game Situations ...in External Load variables and Organizational variables used by a coach for the planning his training for a children basketball team. A total of 15 training tasks, made up 91 tasks were analyzed during the 2019/2020 season, registered through the Integral Analysis System of Training (SIATE). A descriptive analysis of variables was conducted, followed by an inferential analysis to identify the relationship and associations between the independent variable and the dependent ones. According to the results, it is concluded that there is a significant relationship between the Game Situation and the External Load variables (Opposition Degree, Task Density, Number of Simultaneous Performers, Competitive Task Load, Cognitive Implication, Task Load and Time Task Load) and Organizational variables (Total Task Time, Explication Time, Use, Participation and Participation Value). The result showed that the External Load and Organizational variables of the training tasks are conditioned by the Game Situation.
This study aims to characterize locations on two-way rural roads where head-on crashes are more likely to occur, attending to geometric road design factors. For this purpose, a case-control study was ...carried out using multiple logistic regression models with variables related to road design parameters, considering several scenarios. The dataset corresponding to cases (places where crashes have occurred) was collected on Spanish “1+1” rural roads over a four-year period. The controls (places where no crashes have occurred in the period) where randomly selected through a specific ad hoc designed method. The obtained model identifies risk factors and allows the computation of the odds of a head-on collision on any specific road section: width of the pavement (when it exceeds 6 m), width of the lanes (for intermediate widths between 3.25 and 3.75 m) and tight curves (less than 250 m of radius) are identified as factors significantly increasing the odds of a crash, whereas a paved shoulder is a protective factor. The identified configurations on two-way rural roads may be susceptible to transformation into “2+1” roads to decrease the odds of a head-on crash, thus preventing possible serious injuries and enhancing transportation safety.
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