Mandatory maternal metabolic and immunological changes are essential to pregnancy success. Parallel changes in metabolism and immune function make immunometabolism an attractive mechanism to enable ...dynamic immune adaptation during pregnancy. Immunometabolism is a burgeoning field with the underlying principle being that cellular metabolism underpins immune cell function. With whole body changes to the metabolism of carbohydrates, protein and lipids well recognised to occur in pregnancy and our growing understanding of immunometabolism as a determinant of immunoinflammatory effector responses, it would seem reasonable to expect immune plasticity during pregnancy to be linked to changes in the availability and handling of multiple nutrient energy sources by immune cells. While studies of immunometabolism in pregnancy are only just beginning, the recognised bi-directional interaction between metabolism and immune function in the metabolic disorder obesity might provide some of the earliest insights into the role of immunometabolism in immune plasticity in pregnancy. Characterised by chronic low-grade inflammation including in pregnant women, obesity is associated with numerous adverse outcomes during pregnancy and beyond for both mother and child. Concurrent changes in metabolism and immunoinflammation are consistently described but any causative link is not well established. Here we provide an overview of the metabolic and immunological changes that occur in pregnancy and how these might contribute to healthy versus adverse pregnancy outcomes with special consideration of possible interactions with obesity.
Metabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of ...metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs.
An obituary for Diana Lee Weinrich who passed away in 2017 at the age of 53 years and who was instrumental in organizing the first Women's Mineral Retreat in Colorado in 2016 is presented.
•miRNAs were profiled in post-mortem brains of people with the NIA-AA A+T+ phenotype.•A high-throughput microarray expression platform and validation assays were used.•Six miRNAs were differentially ...expressed compared to age- and sex-matched donors.•Bioinformatics implicated 3 miRNAs, 7 target genes and 11 pathways with AD pathology.•Such dysregulation suggests apoptosis, autophagy and oxidation in the CNS.
MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer’s disease (AD).
to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD.
A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo’s Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples.
The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology.
A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.
The death of Diana, Princess of Wales, on September 1 1997, prompted public demonstrations of grief on an almost unprecented global scale. But, while global media coverage of the events following her ...death appeared to create an international 'community of mourning', popular reacions in fact reflected the complexities of the princess's public image and the tensions surrounding the popular conception of royalty. Mourning Diana examines the events which followed the death of Diana as a series of cultural-political phenomena, from the immediate aftermath as crowds gathered in public spaces and royal palaces, to the state funeral in Westminister Abbey, examining the performance of grief and the involvement of the global media in the creation of narratives and spectacles relating to the commemoration of her life. Contributors investigate the complex iconic status of Diana, as a public figure able to sustain a host of alternative identifications, and trace the posthumous romanticisation of aspects of her life such as her charity activism and her relationship with Dodi al Fayed. The contributors argue that the events following the death of Diana dramatised a complex set of cultural tensions in which the boundaries dividing nationhood and citizenship, charity and activism, private feeling and public politics, were redrawn.
Early childhood education and care has been a political priority in England since 1997, when government finally turned its attention to this long-neglected area. Public funding has increased, policy ...initiatives have proliferated and at each general election political parties aim to outbid each other in their offer to families. Transforming Early Childhood in England: Towards a Democratic Education argues that, despite this attention, the system of early childhood services remains flawed and dysfunctional. National discourse is dominated by the cost and availability of childcare at the expense of holistic education, while a hotchpotch of fragmented provision staffed by a devalued workforce struggles with a culture of targets and measurement. With such deep-rooted problems, early childhood education and care in England is beyond minor improvements. In the context of austerity measures affecting many young families, transformative change is urgent. Transforming Early Childhood in England offers a critical analysis of the current system and proposes change based on young children’s universal right to education. The book calls for provision built on democratic principles, where all learning by all children is visible and recognised, educators are trusted and respected, and a calmer approach called ‘slow pedagogy’ replaces outcomes-driven targets. Combining criticism and hope, and drawing on inspiring research and examples from home and abroad, the book is essential reading for students, educators, practitioners, parents, academics and policymakers - anyone, in fact, who seeks to understand the policy problems for early childhood education and care in England, and see better prospects for the future.
The critical role developed by dendritic cell (DC) in the orchestration of immune response explains its exploitation in different therapeutic approaches as potential vaccine tools. Various clinical ...trials dissect its role in different types of solid cancers. However, there is a lack of comprehension regarding the potential impact of DC metabolic pathways on the effectiveness of DC vaccine. In this review, we intend to dissect how metabolism could be a critical component of DC vaccine formulation, exploring opportunities to improve: (i) processing and cross-presentation of tumour antigens; (ii) DC migration, and (iii) DC immunogenic profile. Overall, we aim to open the discussion to explore new avenues/paths where DC metabolism might be considered a core component of antitumour DC vaccine with this review.
The paper represents the first attempt of interpretation and contextualization of Diana’s sanctuary in late antique Doclea, through re-examination of its particular architectural features, which have ...been documented by archaeologists through the past 131 years. We offer an integral picture of the temple and its temenos, thus once again confirming that the sanctuary was actually a part of large-scale imperial interventions into the urban fabric of the town — those of Emperor Gaius Aurelius Valerius Diocletianus. We substantiate the hypothesis that the temple was a creation of distinctive, highly innovative and original, Diocletian’s “architectural school” of planners, builders and stonemasons.
Rad predstavlja prvo nastojanje da se protumači i kontekstualizira Dijanino svetište u kasnoantičkoj Dokleji, te ponovno razmotre njegove specifične arhitektonske karakteristike, koje su arheolozi zabilježili tijekom proteklih 131 godinu. Ponuđena je cjelovita slika hrama i njegova posvećenog okruženja, čime se još jednom potvrđuje da je uređenje svetišta bilo dio šireg carskog zahvata u urbano tkivo grada, poduzeto u doba Dioklecijana (Gaius Aurelius Valerius Diocletianus). Potvrđuje se pretpostavka da je hram bilo djelo osobite, inovativne i originalne Dioklecijanove „graditeljske radionice”.
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