Abstract Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. ...The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions.
Mass spectrometry- and nuclear magnetic resonance-based metabolomic studies comparing diseased versus healthy individuals have shown that microbial metabolites are often the compounds most markedly ...altered in the disease state. Recent studies suggest that several of these metabolites that derive from microbial transformation of dietary components have significant effects on physiological processes such as gut and immune homeostasis, energy metabolism, vascular function, and neurological behavior. Here, we review several of the most intriguing diet-dependent metabolites that may impact host physiology and may therefore be appropriate targets for therapeutic interventions, such as short-chain fatty acids, trimethylamine N-oxide, tryptophan and tyrosine derivatives, and oxidized fatty acids. Such interventions will require modulating either bacterial species or the bacterial biosynthetic enzymes required to produce these metabolites, so we briefly describe the current understanding of the bacterial and enzymatic pathways involved in their biosynthesis and summarize their molecular mechanisms of action. We then discuss in more detail the impact of these metabolites on health and disease, and review current strategies to modulate levels of these metabolites to promote human health. We also suggest future studies that are needed to realize the full therapeutic potential of targeting the gut microbiota.
Although the relative importance of airborne transmission of the SARS-CoV-2 virus is controversial, increasing evidence suggests that understanding airflows is important for estimation of the risk of ...contracting COVID-19. The data available so far indicate that indoor transmission of the virus far outstrips outdoor transmission, possibly due to longer exposure times and the decreased turbulence levels (and therefore dispersion) found indoors. In this paper we discuss the role of building ventilation on the possible pathways of airborne particles and examine the fluid mechanics of the processes involved.
Abstract
The third observing run of Advanced LIGO and Advanced Virgo took place between 2019 April and 2020 March and resulted in dozens of gravitational-wave candidates, many of which are now ...published as confident detections. A crucial requirement of the third observing run was the rapid identification and public reporting of compact binary mergers, which enabled massive follow-up observation campaigns with electromagnetic and neutrino observatories. PyCBC Live is a low-latency search for compact binary mergers based on frequency-domain matched filtering, which was used during the second and third observing runs, together with other low-latency analyses, to generate these rapid alerts from the data acquired by LIGO and Virgo. This paper describes and evaluates the improvements made to PyCBC Live after the second observing run, which defined its operation and performance during the third observing run.
We present the second Open Gravitational-wave Catalog (2-OGC) of compact-binary coalescences, obtained from the complete set of public data from Advanced LIGO's first and second observing runs. For ...the first time we also search public data from the Virgo observatory. The sensitivity of our search benefits from updated methods of ranking candidate events including the effects of nonstationary detector noise and varying network sensitivity; in a separate targeted binary black hole merger search we also impose a prior distribution of binary component masses. We identify a population of 14 binary black hole merger events with probability of astrophysical origin >0.5 as well as the binary neutron star merger GW170817. We confirm the previously reported events GW170121, GW170304, and GW170727 and also report GW151205, a new marginal binary black hole merger with a primary mass of that may have formed through hierarchical merger. We find no additional significant binary neutron star merger or neutron star-black hole merger events. To enable deeper follow-up as our understanding of the underlying populations evolves, we make available our comprehensive catalog of events, including the subthreshold population of candidates and posterior samples from parameter inference of the 30 most significant binary black hole candidates.
One mechanism by which early life environment may influence long term health is through modulation of the gut microbiota. It is widely accepted that the optimal source of nutrition in early life is ...breast milk, with Human Milk Oligosaccharides (HMOs) thought to play an important role in nourishing the developing microbiota. However, mothers with inactive secretor genes have altered HMO composition and quantities in their breast milk. In this pilot study we examine the influence of secretor status and breast-feeding on microbiota composition at 2 to 3 years of age.
37 children and 17 eligible mothers were recruited. Secretor status was determined from blood and saliva samples using hemagglutination inhibition technique and faecal microbiota composition was examined by 16S rRNA gene sequencing.
Secretor status was determined for 28 eligible children with 20 being secretors (S, 71.4%). Eleven of the 17 mothers were secretors (S, 64.7%). Unweighted UniFrac distances were significantly associated with child secretor status (R2 = 0.069, p = 0.030) and with mother secretor status in children exclusively breastfed for at least 4 months (R2 = 0.167, p = 0.028), suggesting an influence on the presence/absence of microbes, with Prevotella not detected in samples from secretor children and children of secretor mothers. In children who were exclusively breast-fed for at least 4 months of life the abundance of the known HMO consumers Bifidobacterium were increased in the children of secretor mothers compared to non-secretor mothers. The relative abundance of an OTU related to Bacteroides plebeius, a bacterium noted for its capacity to utilise sulphated polysaccharides for growth, was decreased in these children.
Child and mothers' secretor status have an impact on childrens' microbiota composition at 2 to 3 years of age.
Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage ...(arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52–98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged‐matched control microglia. In AD cases, on average, 49%–64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged‐matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging‐related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural‐glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease.
Theories heralding the rise of network governance have dominated for a generation. Yet, empirical research suggests that claims for the transformative potential of networks are exaggerated. This ...topical and timely book takes a critical look at contemporary governance theory, elaborating a Gramscian alternative. It argues that, although the ideology of networks has been a vital element in the neoliberal hegemonic project, there are major structural impediments to accomplishing it. While networking remains important, the hierarchical and coercive state is vital for the maintenance of social order and integral to the institutions of contemporary governance. Reconsidering it from Marxist and Gramscian perspectives, the book argues that the hegemonic ideology of networks is utopian and rejects the claim that there has been a transformation from 'government' to 'governance'. This important book has international appeal and will be essential reading for scholars and students of governance, public policy, human geography, public management, social policy and sociology.
The worldwide advanced gravitational-wave (GW) detector network has so far primarily consisted of the two Advanced LIGO observatories at Hanford and Livingston, with Advanced Virgo joining the 2016-7 ...O2 observation run at a relatively late stage. However Virgo has been observing alongside the LIGO detectors since the start of the O3 run; in the near future, the KAGRA detector will join the global network and a further LIGO detector in India is under construction. Gravitational-wave search methods would therefore benefit from the ability to analyse data from an arbitrary network of detectors. In this paper, we extend the PyCBC offline compact binary coalescence (CBC) search analysis to three or more detectors, and describe resulting updates to the coincident search and event ranking statistic. For a three-detector network, our improved multi-detector search finds 23% more simulated signals at fixed false alarm rate in idealized colored Gaussian noise, and up to 40% more in real data, compared to the two-detector analysis previously used during O2.
Stable isotopes have been used as tracers in human nutritional studies for many years. A number of isotopes have been used frequently to assess body composition, energy expenditure, protein turnover ...and metabolic studies in general, such as deuterium (
Hydrogen),
Oxygen,
Carbon and
Nitrogen. Nevertheless, there is still occasional confusion and concern over their safety, which can hinder the appropriate use of these isotopes in human studies. This mini review aims, therefore, to consider the safety of the four stable isotopes mentioned above, and to reiterate and reaffirm their safety once again. It is hoped that these data will be of use to new researchers in the field, as well as those considering the ethical or other implications of using these stable isotopes in nutritional research. Undoubtedly some of the confusion arises as deuterium, especially, is associated with the nuclear industry. However, as their name implies, of course, none of these stable isotopes are radioactive, and no adverse biological or physiological effects have been reported at the very low levels of enrichment that are used in human studies. There are ample data to reaffirm the safety of stable isotopes at the levels used in nutritional research, and unnecessary concerns and/or confusion should not be a block to continued use of these important tracers.
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