Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major ...sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products. One of the most abundant and cytotoxic lipid -derived aldehydes is 4-hydroxy 2-nonenal (HNE). HNE toxicity is mainly due to the alterations of cell functions by the formation of covalent adducts of HNE with proteins. A key marker of lipid peroxidation, HNE-protein adducts, were found to be elevated in brain tissues and body fluids of Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis subjects and/or models of the respective age-related neurodegenerative diseases. Although only a few proteins were identified as common targets of HNE modification across all these listed disorders, a high overlap of these proteins occurs concerning the alteration of common pathways, such as glucose metabolism or mitochondrial function that are known to contribute to cognitive decline. Within this context, despite the different etiological and pathological mechanisms that lead to the onset of different neurodegenerative diseases, the formation of HNE-protein adducts might represent the shared leit-motif, which aggravates brain damage contributing to disease specific clinical presentation and decline in cognitive performance observed in each case.
HNE-protein adducts were found to be elevated in brain tissues and body fluids of AD, PD, HD and ALS subjects and/or models of these diseases. This pathogenic event represents a sharedleitmotif, which contributes to brain damage and loss of cognitive performance. Display omitted
•HNE levels are increased in brain and body fluids of AD, PD, HD and ALS pathology.•Increased HNE levels promote brain damage thus worsening cognitive/motor functions.•HNE-modified proteins may be good therapeutic targets for these diseases.
Impairments in neuronal intracellular calcium (
Ca
) handling may contribute to Alzheimer's disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD ...progression, and mitochondrial calcium (
Ca
) signaling is a key regulator of both of these processes. Here, we report remodeling of the
Ca
exchange machinery in the prefrontal cortex of individuals with AD. In the 3xTg-AD mouse model impaired
Ca
efflux capacity precedes neuropathology. Neuronal deletion of the mitochondrial Na
/Ca
exchanger (NCLX, Slc8b1 gene) accelerated memory decline and increased amyloidosis and tau pathology. Further, genetic rescue of neuronal NCLX in 3xTg-AD mice is sufficient to impede AD-associated pathology and memory loss. We show that
Ca
overload contributes to AD progression by promoting superoxide generation, metabolic dysfunction and neuronal cell death. These results provide a link between the calcium dysregulation and metabolic dysfunction hypotheses of AD and suggest
Ca
exchange as potential therapeutic target in AD.
Priming effects (PEs) are defined as short-term changes in the turnover of soil organic matter (SOM) caused by the addition of easily degradable organic compounds to the soil. PEs are ubiquitous but ...the direction (acceleration or retardation of SOM decomposition) and magnitude are not easy to predict. It has been suggested that the ratio between the amount of added PE-triggering substrate to the size of initial soil microbial biomass is an important factor influencing PEs. However, this is mainly based on comparison of different studies and not on direct experimentation. The aim of the current study is to examine the impact of glucose-to-microbial biomass ratios on PEs for three different ecosystems. We did this by adding three different amounts of 13C-glucose with or without addition of mineral N (NH4NO3) to soils collected from arable lands, grasslands and forests. The addition of 13C-glucose was equivalent to 15%, 50% and 200% of microbial biomass C. After one month of incubation, glucose had induced positive PEs for almost all the treatments, with differences in magnitude related to the soil origin and the amount of glucose added. For arable and forest soils, the primed C increased with increasing amount of glucose added, whereas for grassland soils this relationship was negative. We found positive correlations between glucose-derived C and primed C and the strength of these correlations was different among the three ecosystems considered. Generally, additions of mineral N next to glucose (C:N = 15:1) had little effect on the flux of substrate-derived C and primed C. Overall, our study does not support the hypothesis that the trigger-substrate to microbial biomass ratio can be an important predictor of PEs. Rather our results indicate that the amount of energy obtained from decomposing trigger substrates is an important factor for the magnitude of PEs.
Abstract
The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding ...genes. APPRIS selects a single protein isoform, the 'principal' isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants.
This article examines the business choices made by independent farming families, when confronting the need to diversify away from traditional agricultural activities by starting farm-based tourism ...businesses. Based on interviews with farm family members who have set up tourism attractions on their farms, and drawing upon the concept of experiential authenticity, the article explores their self-conceptions of their family identities. In so doing, it addresses the choices and dilemmas facing farm families who attempt diversification through the tourism attraction route, and considers how this affects their attitudes towards more traditional farming activities. Using qualitative case study data, an empirically grounded framework is proposed that expresses the choices and challenges facing tourism entrepreneurial family farm members in the UK, through the conceptual lens of experiential authenticity.
► Conceptualises dilemmas faced by farmers diversifying into tourism attractions. ► Presents attitudes towards traditional farming activities. ► Demonstrates discomfort farmers who have diversified into tourism feel with their choice, leading to staged authenticity and threats to self-identity. ► Explores challenge to business of farm tourism from pressures to diversify.
We detected Crimean-Congo hemorrhagic fever virus in a Hyalomma rufipes nymph collected from a whinchat (Saxicola rubetra) on the island of Ventotene in April 2017. Partial genome sequences suggest ...the virus originated in Africa. Detection of the genome of this virus in Italy confirms its potential dispersion through migratory birds.
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss due to aberrant accumulation of misfolded proteins inside and outside neurons and glial cells, ...leading to a loss of cellular protein homeostasis. Today, no therapy is available to block or slow down AD progression, and the mechanisms of the disease are not fully understood. Autophagy is an intracellular degradation pathway crucial to maintaining cellular homeostasis by clearing damaged organelles, pathogens, and unwanted protein aggregates. In recent years, autophagy dysfunction has gained considerable attention in AD and other neurodegenerative diseases because it has been linked to the accumulation of misfolded proteins that ultimately causes neuronal death in many of these disorders. Interestingly, autophagy-activating compounds have also shown some promising results in both clinical trials and preclinical studies. This review aims at summarizing the current knowledge on autophagy dysfunction in the context of AD pathophysiology, providing recent mechanistic insights on AD-mediated autophagic flux disruption and highlighting potential and novel therapeutic opportunities that target this system for AD therapy.
Self-report questionnaires are the most commonly used personality assessment despite longstanding concerns that self-report responses may be distorted by self-protecting motives and response biases. ...In a large-scale meta-analysis (N = 33,033; k = 152 samples), we compared the means of self- and informant reports of the same target’s Big Five personality traits to examine the discrepancies in two rating sources and whether people see themselves more positively than they are seen by others. Inconsistent with a general self-enhancement effect, results showed that self-report means generally did not differ from informant-report means (average δ = −.038). Moderate mean differences were found only when we compared self-reports with stranger reports, suggesting that people are critical of unacquainted targets. We discuss implications of these findings for personality assessment and other fields in which self-enhancement motives are relevant.
Choice of pricing strategy plays a central role in value creation and the effective functioning of markets. Shifts in technology and the growing availability of data are facilitating ever more ...innovative forms of pricing strategy. Within the emerging literature on pricing ethics, there is a gap in our understanding of the specific challenges of algorithmically generated dynamic pricing. Increasing pricing automation shifts the managerial focus from the selection of prices to the choice of algorithms. This paper expands the literature on pricing ethics by conceptualizing the ethical challenges raised by the contemporary use of dynamic pricing. We propose a governance model for algorithmically generated dynamic pricing, taking into account the role of the customer as a stakeholder in value generation.
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