Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
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From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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Species responding differently to climate change form ‘transient communities’, communities with constantly changing species composition due to colonization and extinction events. Our goal is to disentangle the mechanisms of response to climate change for terrestrial species in these transient communities and explore the consequences for biodiversity conservation. We review spatial escape and local adaptation of species dealing with climate change from evolutionary and ecological perspectives. From these we derive species vulnerability and management options to mitigate effects of climate change. From the perspective of transient communities, conservation management should scale up static single species approaches and focus on community dynamics and species interdependency, while considering species vulnerability and their importance for the community. Spatially explicit and frequent monitoring is vital for assessing the change in communities and distribution of species. We review management options such as: increasing connectivity and landscape resilience, assisted colonization, and species protection priority in the context of transient communities.
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Dit artikel onderzoekt immuniteit buiten de contouren van een menselijk lichaam en een biopolitiek kader in het plantwetenschappelijk materieel-discursief object van het superonkruid met zijn resistentie en tolerantie voor herbiciden. In plaats van categorisch aan te nemen dat alle vormen van immuniteit en immuunsystemen plaatsvinden binnen de abstracte categorie van het (menselijk) lichaam, besteedt het artikel aandacht aan de manier waarop het superonkruid als analytisch en synthetiserend brandpunt het concept van immuniteit gaat bevolken en erdoor bevolkt wordt. In het algemeen beweert de auteur dat de materiële dimensie van het superonkruid kan worden gezien als een uitbreiding van of aanvulling op noties van het individuele, autonome en begrensde menselijke lichaam, maar dat deze materiële dimensie ook zijn eigen subjectpositie kan ondermijnen. Door het concept van immuniteit los te koppelen van zijn 'oorsprong' in het menselijk lichaam, kunnen nieuwe ontologische gronden voor menselijke en niet-menselijke politieke ecologieën worden bedacht, met een andere vorm van belichaming, die noch negatief, noch bevestigend zijn.
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ENGLISH: A vast and growing body of research has shown that crime tends to run in families. However, previous studies focused only on traditional crimes and research on familial risk factors for cyber offending is very scarce. To address this gap in the literature, the present study examines the criminal behavior of the family members of a sample of cyber offenders prosecuted in the Netherlands. The sample consists of 979 cyber offenders prosecuted for computer trespassing between 2001 and 2018, and two matched groups of 979 traditional offenders and 979 non-offenders. Judicial information and kinship data from Dutch Statistics were used to measure criminal behavior among family members. Both traditional offenders and cyber offenders were found to be more likely to have criminal fathers, mothers, and siblings than non-offenders. Additional analyses, however, showed different patterns between cyber offenders who were only prosecuted for cyber offenses and those who also committed traditional crimes. While the former group of cyber offenders were similar to non-offenders in terms of family offending, the latter group of cyber offenders were more similar to traditional offenders. Overall, these results suggest that the traditional mechanisms of intergenerational transmission of crime can only partially explain cybercrime involvement. NEDERLANDS: Uit een groot en groeiend aantal onderzoeken blijkt dat criminaliteit vaak in families voorkomt. Eerdere studies richtten zich echter alleen op traditionele misdrijven en onderzoek naar familiaire risicofactoren voor cybercriminaliteit is zeer schaars. Om deze leemte in de literatuur op te vullen, onderzoekt deze studie het criminele gedrag van familieleden van een steekproef van cyberdelinquenten die in Nederland worden vervolgd. De steekproef bestaat uit 979 cyberdelinquenten die tussen 2001 en 2018 zijn vervolgd voor computervredebreuk, en twee gematchte groepen van 979 traditionele delinquenten en 979 niet-delinquenten. Justitiële informatie en verwantschapsgegevens van het Centraal Bureau voor de Statistiek werden gebruikt om crimineel gedrag onder familieleden te meten. Zowel traditionele daders als cybercriminelen bleken vaker criminele vaders, moeders en broers en zussen te hebben dan niet-daders. Aanvullende analyses lieten echter verschillende patronen zien tussen cyberdelinquenten die alleen werden vervolgd voor cyberdelicten en degenen die ook traditionele delicten pleegden. Terwijl de eerste groep cyberdelinquenten vergelijkbaar was met niet-delinquenten wat betreft gezinsdelinquentie, leek de tweede groep cyberdelinquenten meer op traditionele delinquenten. In het algemeen suggereren deze resultaten dat de traditionele mechanismen van intergenerationele overdracht van criminaliteit de betrokkenheid bij cybercriminaliteit slechts gedeeltelijk kunnen verklaren.
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Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.
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The evolution of emerging technologies that use Radio Frequency Electromagnetic Field (RF-EMF) has increased the interest of the scientific community and society regarding the possible adverse effects on human health and the environment. This article provides NextGEM’s vision to assure safety for EU citizens when employing existing and future EMF-based telecommunication technologies. This is accomplished by generating relevant knowledge that ascertains appropriate prevention and control/actuation actions regarding RF-EMF exposure in residential, public, and occupational settings. Fulfilling this vision, NextGEM commits to the need for a healthy living and working environment under safe RF-EMF exposure conditions that can be trusted by people and be in line with the regulations and laws developed by public authorities. NextGEM provides a framework for generating health-relevant scientific knowledge and data on new scenarios of exposure to RF-EMF in multiple frequency bands and developing and validating tools for evidence-based risk assessment. Finally, NextGEM’s Innovation and Knowledge Hub (NIKH) will offer a standardized way for European regulatory authorities and the scientific community to store and assess project outcomes and provide access to findable, accessible, interoperable, and reusable (FAIR) data.
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Background: Parents of children with profound intellectual and multiple disabilities (PIMD) have extensive care duties. This study describes the phenomenon “parenting a child with PIMD.” Method: We conducted in-depth interviews with 25 Dutch parents. A reflective lifeworld research. Findings: The essential meaning of the phenomenon was understood as “continuously struggling to create and maintain new equilibriums that protect the child and the family from hardship; changing in context through time.” The following eight constituents were identified: (1) medical complexity; (2) multidimensional weariness; (3) care for siblings; (4) social connectedness; (5) uncertainty about the future; (6) wrecking bureaucracy; (7) dependency on healthcare delivery; and (8) financial concerns. Conclusions: Healthcare services should provide families with easy access to assistive technology and services needed to manage family life. Responsiveness to parents’ challenges offers them the possibility to participate in society. Healthcare professionals should address the parents’ perspectives related to the child’s quality of life.
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Immunofluorescence microscopy in this study shows that GLUT-4 protein expression is fibre-type specific within a muscle. It is postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression.
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The full potential of predictive maintenance has not yet been utilised. Current solutions focus on individual steps of the predictive maintenance cycle and only work for very specific settings. The overarching challenge of predictive maintenance is to leverage these individual building blocks to obtain a framework that supports optimal maintenance and asset management. The PrimaVera project has identified four obstacles to tackle in order to utilise predictive maintenance at its full potential: lack of orchestration and automation of the predictive maintenance workflow, inaccurate or incomplete data and the role of human and organisational factors in data-driven decision support tools. Furthermore, an intuitive generic applicable predictive maintenance process model is presented in this paper to provide a structured way of deploying predictive maintenance solutions https://doi.org/10.3390/app10238348 LinkedIn: https://www.linkedin.com/in/john-bolte-0856134/
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