Still a house divided King, Desmond S; Smith, Rogers M
2011., 20110822, 2011, 2011-08-22, Volume:
125
eBook
Why have American policies failed to reduce the racial inequalities still pervasive throughout the nation? Has President Barack Obama defined new political approaches to race that might spur unity ...and progress? Still a House Divided examines the enduring divisions of American racial politics and how these conflicts have been shaped by distinct political alliances and their competing race policies. Combining deep historical knowledge with a detailed exploration of such issues as housing, employment, criminal justice, multiracial census categories, immigration, voting in majority-minority districts, and school vouchers, Desmond King and Rogers Smith assess the significance of President Obama's election to the White House and the prospects for achieving constructive racial policies for America's future.
Hydrogen sulfide, an important gaseous signaling agent generated in numerous biological tissues, influences many physiological processes. This biological profile seems reminiscent of nitric oxide, ...another important endogenously synthesized gaseous signaling molecule. Hydrogen sulfide reacts with nitric oxide or oxidized forms of nitric oxide and nitric oxide donors in vitro to form species that display distinct biology compared to both hydrogen sulfide and NO. The products of these interesting reactions may include small-molecule S-nitrosothiols or nitroxyl, the one-electron-reduced form of nitric oxide. In addition, thionitrous acid or thionitrite, compounds structurally analogous to nitrous acid and nitrite, may constitute a portion of the reaction products. Both the chemistry and the biology of thionitrous acid and thionitrite, compared to nitric oxide or hydrogen sulfide, remain poorly defined. General mechanisms for the formation of S-nitrosothiols, nitroxyl, and thionitrous acid based upon the ability of hydrogen sulfide to act as a nucleophile and a reducing agent with reactive nitric oxide-based intermediates are proposed. Hydrogen sulfide reactivity seems extensive and could have an impact on numerous areas of redox-controlled biology and chemistry, warranting more work in this exciting and developing area.
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► Hydrogen sulfide behaves as a nucleophile and a reducing agent. ► Hydrogen sulfide decreases the amount of nitric oxide released by NO donors. ► Hydrogen sulfide alters the normally observed biological response of nitric oxide. ► S-nitrosothiols and nitroxyl probably form from hydrogen sulfide and nitric oxide. ► Hydrogen sulfide reacts with S-nitrosothiols by trans-nitrosation or displacement.
The origins and evolution of macropinocytosis King, Jason S; Kay, Robert R
Philosophical transactions - Royal Society. Biological sciences,
02/2019, Volume:
374, Issue:
1765
Journal Article
Peer reviewed
Open access
In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds ...extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
We study an extended 2 Higgs doublet model (2HDM) in which the Standard Model (SM) Yukawa interactions are forbidden due to a global U(1)' symmetry, but may arise via mixing with vectorlike families. ...In this model, the hierarchical structure of Yukawa couplings of quarks and leptons in the SM arises from the heavy masses of the fourth and fifth vectorlike families. Within this model, we consider various nonstandard contributions to the electron and muon anomalous magnetic moments. We first consider the W exchange at one-loop level, consistent with the μ → eγ constraint, and show that it yields a negligible contribution to both electron and muon anomalous magnetic moments. We then consider Higgs scalar exchange, together with vectorlike leptons, at one-loop level and show that it is possible to have nonstandard contributions to the electron and muon anomalous magnetic moments within the 1σ constraint of certain experiments. We present some benchmark points for both the muon and the electron anomalies, together with some numerical scans around these points, which indicate the mass regions of the Higgs scalars of the 2HDM in this scenario.
Acute respiratory distress syndrome (ARDS) is a devastating disease with distinct pathological stages. Fundamental to ARDS is the acute onset of lung inflammation as a part of the body's immune ...response to a variety of local and systemic stimuli. In patients surviving the inflammatory and subsequent fibroproliferative stages, transition from injury to resolution and recovery is an active process dependent on a series of highly coordinated events regulated by the immune system. Experimental animal models of acute lung injury (ALI) reproduce key components of the injury and resolution phases of human ARDS and provide a methodology to explore mechanisms and potential new therapies. Macrophages are essential to innate immunity and host defense, playing a featured role in the lung and alveolar space. Key aspects of their biological response, including differentiation, phenotype, function, and cellular interactions, are determined in large part by the presence, severity, and chronicity of local inflammation. Studies support the importance of macrophages to initiate and maintain the inflammatory response, as well as a determinant of resolution of lung inflammation and repair. We will discuss distinct roles for lung macrophages during early inflammatory and late resolution phases of ARDS using experimental animal models. In addition, each section will highlight human studies that relate to the diverse role of macrophages in initiation and resolution of ALI and ARDS.
In order to address this question, we consider a simple renormalizable and gauge invariant model in which the Z′ only has couplings to the electron and muon and their associated neutrinos, arising ...from mixing with a heavy vectorlike fourth family of leptons. Within this model we discuss the contributions to the electron and muon anomalous magnetic moments from Z′ exchange, subject to the constraints from μ → e γ and neutrino trident production. Using analytic and numerical arguments, we find that such a Z′ model can account for either the electron or the muon g − 2 anomalies, but not both, while remaining consistent with the experimental constraints from μ → eγ and neutrino trident production.
Macropinocytosis is a mechanism for the nonspecific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic ...cells and neurons, by allowing cells to sample their environment, extract extracellular nutrients and regulate plasma membrane turnover. Macropinocytosis has recently been implicated in several diseases including cancer, neurodegenerative diseases and atherosclerosis. Uptake by macropinocytosis is also exploited by several intracellular pathogens to gain entry into host cells. Both capturing and subsequently processing large volumes of extracellular fluid poses a number of unique challenges for the cell. Macropinosome formation requires coordinated three‐dimensional manipulation of the cytoskeleton to form shaped protrusions able to entrap extracellular fluid. The following maturation of these large vesicles then involves a complex series of membrane rearrangements to shrink and concentrate their contents, while delivering components required for digestion and recycling. Recognition of the diverse importance of macropinocytosis in physiology and disease has prompted a number of recent studies. In this article, we summarise advances in our understanding of both macropinosome formation and maturation, and seek to highlight the important unanswered questions.
The bulk ingestion of extracellular fluid by macropinocytosis serves many functions in both normal physiology and disease. Here we describe recent advances in our understanding of how the protrusions required to capture the fluid are generated, as well as how cells process these large aqueous vesicles after internalisation.
We present monthly maps and derived statistics to describe the large-area distribution of Sargassum in the equatorial Atlantic, Caribbean, and Gulf of Mexico, using image data from the OLCI (Ocean ...and Land Colour Instrument) on the Sentinel 3a satellite. OLCI has provided image data since October 2016 which can be compared with images produced by MERIS (Medium Resolution Imaging Spectrometer) in the period 2002 to 2012. Results show a significant and continuing increase of the area covered by pelagic Sargassum, starting from a first expansion into the Caribbean and equatorial Atlantic in 2011. We use results from a global detection scheme based on the MCI (Maximum Chlorophyll Index) derived from MERIS and OLCI and implemented by ESA's Grid Processing on Demand (GPOD) project. The scheme uses the OLCI image data set at the reduced resolution of 1200m to give monthly global composite images at 5km spatial resolution, designed to record location, extent and intensity of intense plankton blooms and floating vegetation. In the present study area, images are dominated by a growing and spreading distribution of pelagic Sargassum, whose origin and annual cycle remain unexplained. The composite images give no indication of similar populations in other parts of the global ocean. Results derived from MERIS and OLCI are consistent with those derived from MODIS and VIIRS.
Despite the development of pharmacological therapies that are effective in slowing the progression of idiopathic pulmonary fibrosis (IPF), it remains a debilitating and lethal condition. In addition ...to the adverse effects caused by pulmonary fibrosis, most patients with IPF have associated comorbid conditions, which might negatively affect functional status, quality of life, and survival. Comorbid conditions can be pulmonary or extrapulmonary. Pulmonary comorbidities include pulmonary hypertension, emphysema, and lung cancer, while non-pulmonary conditions include venous thromboembolism, coronary artery disease, congestive heart failure, sleep-disordered breathing, gastro-oesophageal reflux disease, and anxiety or depression. Although some of these comorbid conditions share risk factors with IPF, the likelihood for their presence or development in patients with IPF is still greater than expected. This might indicate that IPF fosters an environment for the development or perpetuation of comorbid conditions, or alternatively that they share causative factors. Optimal management of IPF therefore requires a comprehensive approach, which includes the identification and treatment of comorbid conditions to optimise patient outcomes.
Phagocytic cells capture and kill most invader microbes within the bactericidal phagosome, but some pathogens subvert killing by damaging the compartment and escaping to the cytosol. To prevent the ...leakage of pathogen virulence and host defence factors, as well as bacteria escape, host cells have to contain and repair the membrane damage, or finally eliminate the cytosolic bacteria. All eukaryotic cells engage various repair mechanisms to ensure plasma membrane integrity and proper compartmentalization of organelles, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. We show that during infection of Dictyostelium discoideum with Mycobacterium marinum, the ESCRT-I component Tsg101, the ESCRT-III protein Snf7/Chmp4/Vps32 and the AAA-ATPase Vps4 are recruited to sites of damage at the Mycobacterium-containing vacuole. Interestingly, damage separately recruits the ESCRT and the autophagy machineries. In addition, the recruitment of Vps32 and Vps4 to repair sterile membrane damage depends on Tsg101 but appears independent of Ca2+. Finally, in absence of Tsg101, M. marinum accesses prematurely the cytosol, where the autophagy machinery restricts its growth. We propose that ESCRT has an evolutionary conserved function to repair small membrane damage and to contain intracellular pathogens in intact compartments.
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