High-density lipoprotein (HDL) particles transport (among other molecules) cholesterol (HDL-C). In epidemiological studies, plasma HDL-C levels have an inverse relationship to the risk of ...atherosclerotic cardiovascular disease. It has been assumed that this reflects the protective functions of HDL, which include their ability to promote cholesterol efflux. Yet, several recent pharmacological and genetic studies have failed to demonstrate that increased plasma levels of HDL-C resulted in decreased cardiovascular disease risk, giving rise to a controversy regarding whether plasma levels of HDL-C reflect HDL function, or that HDL is even as protective as assumed. The evidence from preclinical and (limited) clinical studies shows that HDL can promote the regression of atherosclerosis when the levels of functional particles are increased from endogenous or exogenous sources. The data show that regression results from a combination of reduced plaque lipid and macrophage contents, as well as from a reduction in its inflammatory state. Although more research will be needed regarding basic mechanisms and to establish that these changes translate clinically to reduced cardiovascular disease events, that HDL can regress plaques suggests that the recent trial failures do not eliminate HDL from consideration as an atheroprotective agent but rather emphasizes the important distinction between HDL function and plasma levels of HDL-C.
The fossil record and macroevolutionary history of the beetles Smith, Dena M.; Marcot, Jonathan D.
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
04/2015, Letnik:
282, Številka:
1805
Journal Article
Recenzirano
Odprti dostop
Coleoptera (beetles) is the most species-rich metazoan order, with approximately 380 000 species. To understand how they came to be such a diverse group, we compile a database of global fossil beetle ...occurrences to study their macroevolutionary history. Our database includes 5553 beetle occurrences from 221 fossil localities. Amber and lacustrine deposits preserve most of the beetle diversity and abundance. All four extant suborders are found in the fossil record, with 69% of all beetle families and 63% of extant beetle families preserved. Considerable focus has been placed on beetle diversification overall, however, for much of their evolutionary history it is the clade Polyphaga that is most responsible for their taxonomic richness. Polyphaga had an increase in diversification rate in the Early Cretaceous, but instead of being due to the radiation of the angiosperms, this was probably due to the first occurrences of beetle-bearing amber deposits in the record. Perhaps, most significant is that polyphagan beetles had a family-level extinction rate of zero for most of their evolutionary history, including across the Cretaceous–Palaeogene boundary. Therefore, focusing on the factors that have inhibited beetle extinction, as opposed to solely studying mechanisms that may promote speciation, should be examined as important determinants of their great diversity today.
It has been widely observed around the world that the frequency and intensity
of new particle formation (NPF) events are reduced during periods of high
relative humidity (RH). The current study ...focuses on how RH affects the
formation of highly oxidized molecules (HOMs), which are key components of
NPF and initial growth caused by oxidized organics. The ozonolysis of
α-pinene, limonene, and Δ3-carene, with and without OH
scavengers, were carried out under low NOx conditions under
a range of RH (from ∼3 % to ∼92 %) in a
temperature-controlled flow tube to generate secondary organic aerosol (SOA).
A Scanning Mobility Particle Sizer (SMPS) was used to measure the size
distribution of generated particles, and a novel transverse ionization
chemical ionization inlet with a high-resolution time-of-fight mass
spectrometer detected HOMs. A major finding from this work is that neither
the detected HOMs nor their abundance changed significantly with RH, which
indicates that the detected HOMs must be formed from water-independent
pathways. In fact, the distinguished OH- and O3-derived peroxy
radicals (RO2), HOM monomers, and HOM dimers could mostly be
explained by the autoxidation of RO2 followed by bimolecular
reactions with other RO2 or hydroperoxy radicals (HO2),
rather than from a water-influenced pathway like through the formation of a
stabilized Criegee intermediate (sCI). However, as RH increased from ∼3 % to ∼92 %, the total SOA number concentrations decreased by
a factor of 2–3 while SOA mass concentrations remained relatively constant. These observations show that, while
high RH appears to inhibit NPF as evident by the decreasing number
concentration, this reduction is not caused by a decrease in
RO2-derived HOM formation. Possible explanations for these phenomena
were discussed.
We present a detailed analysis of the picosecond-to-nanosecond motions of green fluorescent protein (GFP) and its hydration water using neutron scattering spectroscopy and hydrogen/deuterium ...contrast. The analysis reveals that hydration water suppresses protein motions at lower temperatures (<∼200 K), and facilitates protein dynamics at high temperatures. Experimental data demonstrate that the hydration water is harmonic at temperatures <∼180–190 K and is not affected by the proteins’ methyl group rotations. The dynamics of the hydration water exhibits changes at ∼180–190 K that we ascribe to the glass transition in the hydrated protein. Our results confirm significant differences in the dynamics of protein and its hydration water at high temperatures: on the picosecond-to-nanosecond timescale, the hydration water exhibits diffusive dynamics, while the protein motions are localized to <∼3 Å. The diffusion of the GFP hydration water is similar to the behavior of hydration water previously observed for other proteins. Comparison with other globular proteins (e.g., lysozyme) reveals that on the timescale of 1 ns and at equivalent hydration level, GFP dynamics (mean-square displacements and quasielastic intensity) are of much smaller amplitude. Moreover, the suppression of the protein dynamics by the hydration water at low temperatures appears to be stronger in GFP than in other globular proteins. We ascribe this observation to the barrellike structure of GFP.
•Diagnoses causes of the difficult relationship between missionaries and development.•Reviews 48 sources proposing and critiquing typologies of faith-based organizations (FBOs).•Finds that FBO ...typologies are based on outdated assumptions separating religious and secular actors.•Proposes a framework to analyze links between beliefs and practices of development for all religious and secular actors.
This article diagnoses major causes of the uncomfortable relationship between missionaries and development scholars and practitioners, and it proposes new ways to clarify the relationship through shared reflection on sacred influences that shape global development. In the past fifteen years the turn to religion in development studies has altered how development scholars and practitioners perceive religious actors, opening up possibilities for renewed partnership. Yet the turn to religion in development has mostly disregarded missionaries. This oversight is partly due to the complicated historical relationship between Western Christian missionaries and development workers. Although missionaries have long participated in the work of development, present-day missionaries remain associated with coercive proselytization, or they are overlooked in literature on religion and development.
In order to understand the challenges of positioning missionaries in development, I review 48 sources which create, apply, or critique typologies of faith-based organizations (FBOs). FBO typologies of the past fifteen years have broken new ground in exploring the links between beliefs and practices of religious actors doing development work. Yet these typologies struggle to position missionaries due to (1) simplistic categorization of FBOs, (2) unhelpful scales of religiosity, and (3) a basis in outdated assumptions of separate spheres of religious and secular actors, and separate worlds of religion and development. Based on shared critiques of FBO typologies, I propose a new framework for positioning missionaries. The framework provides a shared space to explore how all development actors, both religious and secular, are shaped by the interaction between sacred and material influences. The framework offers a way to move beyond circular arguments about comparative advantage of religious or secular approaches toward an appreciation of the complementarity of different approaches to development. The article concludes with a shared critique of missionaries and development workers who impose their beliefs and values on others.
OBJECTIVE—Sphingomyelin deposition and metabolism occurs in the atherosclerotic plaque, leading to the formation of sphingosine-1-phosphate (S1P), which activates G protein–coupled receptors to ...regulate vascular and immune cells. The role of S1P receptors in atherosclerosis has not been examined.
METHODS AND RESULTS—We tested the hypothesis that S1P receptor-2 (S1PR2) regulates atherosclerosis. Apoe S1pr2 mice showed greatly attenuated atherosclerosis compared with the Apoe mice. Bone marrow transplant experiments indicate that S1PR2 function in the hematopoietic compartment is critical. S1PR2 is expressed in bone marrow–derived macrophages and in macrophage-like foam cells in atherosclerotic plaques. Reduced macrophage-like foam cells were found in the atherosclerotic plaques of ApoeS1pr2 mice, suggesting that S1PR2 retains macrophages in atherosclerotic plaques. Lipoprotein profiles, plasma lipids, and oxidized low-density lipoprotein uptake by bone marrow–derived macrophages were not altered by the S1pr2 genotype. In contrast, endotoxin-induced inflammatory cytokine (interleukin IL-1β, IL-18) levels in the serum of S1PR2 knockout mice were significantly reduced. Furthermore, treatment of wild-type mice with S1PR2 antagonist JTE-013 suppressed IL-1β and IL-18 levels in plasma.
CONCLUSION—These data suggest that S1PR2 signaling in the plaque macrophage regulates macrophage retention and inflammatory cytokine secretion, thereby promoting atherosclerosis.
The mixed morphology class of supernova remnants has centrally peaked X-ray emission along with a shell-like morphology in radio emission. White & Long proposed that these remnants are evolving in a ...cloudy medium wherein the clouds are evaporated via thermal conduction once being overrun by the expanding shock. Their analytical model made detailed predictions regarding temperature, density, and emission profiles as well as shock evolution. We present numerical hydrodynamical models in 2D and 3D including thermal conduction, testing the White & Long model and presenting results for the evolution and emission from remnants evolving in a cloudy medium. We find that, while certain general results of the White & Long model hold, such as the way the remnants expand and the flattening of the X-ray surface brightness distribution, in detail there are substantial differences. In particular we find that the X-ray luminosity is dominated by emission from shocked cloud gas early on, leading to a bright peak, which then declines and flattens as evaporation becomes more important. In addition, the effects of thermal conduction on the intercloud gas, which is not included in the White & Long model, are important and lead to further flattening of the X-ray brightness profile as well as lower X-ray emission temperatures.
The sphingosine 1-phosphate receptor 1 (S1P1) is abundant in endothelial cells, where it regulates vascular development and microvascular barrier function. In investigating the role of endothelial ...cell S1P1 in adult mice, we found that the endothelial S1P1 signal was enhanced in regions of the arterial vasculature experiencing inflammation. The abundance of proinflammatory adhesion proteins, such as ICAM-1, was enhanced in mice with endothelial cell-specific deletion of S1pr1 and suppressed in mice with endothelial cell-specific overexpression of S1pr1, suggesting a protective function of S1P1 in vascular disease. The chaperones ApoM(+)HDL (HDL) or albumin bind to sphingosine 1-phosphate (S1P) in the circulation; therefore, we tested the effects of S1P bound to each chaperone on S1P1 signaling in cultured human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to ApoM(+)HDL-S1P, but not to albumin-S1P, promoted the formation of a cell surface S1P1-β-arrestin 2 complex and attenuated the ability of the proinflammatory cytokine TNFα to activate NF-κB and increase ICAM-1 abundance. Although S1P bound to either chaperone induced MAPK activation, albumin-S1P triggered greater Gi activation and receptor endocytosis. Endothelial cell-specific deletion of S1pr1 in the hypercholesterolemic Apoe(-/-) mouse model of atherosclerosis enhanced atherosclerotic lesion formation in the descending aorta. We propose that the ability of ApoM(+)HDL to act as a biased agonist on S1P1 inhibits vascular inflammation, which may partially explain the cardiovascular protective functions of HDL.
It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus ...disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens.
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•T cells with a unique metabolic profile are expanded in acute COVID-19•These T cells are prone to mitochondrial apoptosis, correlating with lymphopenia•Metabolically distinct myeloid-derived suppressor cells increase in acute COVID-19•The presence of these M-MDSCs in acute COVID-19 correlates with disease severity
The precise immunological defects that correlate with disease severity in COVID-19 have yet to be determined. Based on immune-metabolic profiling, Thompson et al. identify unique populations of T cells and myeloid cells that correlate with disease severity. These findings highlight metabolic pathways as possible therapeutic targets for COVID-19.
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