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Madam President : the secret presidency of Edith Wilson
An up-close look at Edith Wilson, a first lady with unequaled responsibilities during her husband's presidency. After President Woodrow Wilson suffered a paralyzing stroke in the fall of 1919, his wife, First Lady Edith Wilson, began to handle the day-to-day responsibilities of the chief executive. Mrs. Wilson had had little formal education and had only been married to President Wilson for four years, yet in the tenuous peace following the end of World War I, she dedicated herself to managing the office of the president, reading all correspondence intended for her bedridden husband. Though her Oval Office authority was acknowledged in Washington circles at the time--one senator called her \"the presidentress who had fulfilled the dream of suffragettes by changing her title from First Lady to Acting First Man\"--Her legacy as the first woman president is now largely forgotten. William Hazelgrove's Madam President is a vivid, engaging portrait of the woman who became the acting president of the United States in 1919, months before women officially won the right to vote.
Book
The international companion to John Galt
John Galt (1779–1839) was a contemporary of Sir Walter Scott and Jane Austen, and a friend and biographer of Lord Byron. Although a prolific writer, and much admired in his own lifetime, Galt has never achieved comparable levels of literary fame, and his works – poised between Enlightenment and Romanticism – are now often overlooked. Yet his reputation has been slowly growing, and he has attracted critical interest as both a political novelist and a chronicler of Scottish life. This International Companion builds on a steady stream of recent scholarship, and examines Galt’s writings in the social, economic, and religious contexts of their time.
eBook
John Galt
This volume offers a revaluation of the work of Romantic-era Scottish writer John Galt. Galt traveled throughout the Mediterranean and Atlantic worlds and founded the Canadian city of Guelph while remaining in touch with local cultures and politics in Scotland and England. He wrote fiction, drama, and biography based on his personal observations of life and in ways that associated him with the “theoretical” or “conjectural” methods of Scottish Enlightenment historiographers. Galt’s insights into the societies he inhabited and visited, his perceptions of political extremism and class conflict, his attitudes toward community building and progress, his convictions about determinism and historical revisionism, his strategies for manipulating literary genres and readers’ responses, and his ambivalence about the value of literature deserve consideration in light of new thinking in our own fields about what constitutes social knowledge and viable ways to represent it. The essays in this volume examine Galt’s work in light of the convergence of literature, history, and social theory in Scottish Enlightenment and Romantic-era culture and in our own interdisciplinary environment. Discussing Galt’s work and significance in the many areas, genres, and contexts in which he figures, they broaden the circle of contacts with whom we associate Galt, moving from expected comparisons with contemporaries Walter Scott and James Hogg to unexpected links with such later authors and social thinkers as George Douglas Brown and Harriet Martineau. Moreover, these essays expand the repertoire of works studied, offering the first extended analyses of Eben Erskine, Rothelan, and the Travels and Observations of Hareach, the Wandering Jew along with new readings of Annals of the Parish, Bogle Corbet, and Ringan Gilhaize. Overall, the essays draw out the implications of Galt’s practices and relations as a journalist, dramatist, critic, biographer, and novelist, developing grounded conjectures about their significance in Galt’s time and our own.
eBook
Dietary mannan oligosaccharides: Counteracting the side effects of soybean oil inclusion on European sea bass (Dicentrarchus labrax) gut health?
The main objective of this study was to assess the effects of 4 g·kg-1dietary MOS inclusion in soybean oil (SBO) and fish oil (FO) based diets on the gut health and skin mucosa mucus production of European sea bass juveniles after 8 weeks of feeding. Dietary MOS, regardless of the oil source, promoted growth. The intestinal somatic index was not affected, however SBO reduced the intestinal fold length, while dietary MOS increased it. The dietary oil source fed produced changes on the posterior intestine fatty acid profiles irrespective of MOS dietary supplementation. SBO down-regulated the gene expression of TCRβ, COX2, IL-1β, TNFα, IL-8, IL-6, IL-10, TGFβ and Ig and up-regulated MHCII. MOS up-regulated the expression of MHCI, CD4, COX2, TNFα and Ig when included in FO based diets. However, there was a minor up-regulating effect on these genes when MOS was supplemented in the SBO based diet. Both dietary oil sources and MOS affected mean mucous cell areas within the posterior gut, however the addition of MOS to a SBO diet increased the mucous cell size over the values shown in FO fed fish. Dietary SBO also trends to reduce mucous cell density in the anterior gut relative to FO, suggesting a lower overall mucosal secretion. There are no effects of dietary oil or MOS in the skin mucosal patterns. Complete replacement of FO by SBO, modified the gut fatty acid profile, altered posterior gut GALT-related gene expression and gut mucous cells patterns, induced shorter intestinal folds and tended to reduce European sea bass growth. However, when combined with MOS, the harmful effects of SBO appear to be partially balanced by moderating the down-regulation of certain GALT-related genes involved in the functioning of gut mucous barrier and increasing posterior gut mucous cell diffusion rates, thus helping to preserve immune homeostasis. This denotes the importance of a balanced dietary n3/n6 ratio for an appropriate GALT-immune response against MOS in European sea bass.
Journal Article
Galactose-1-phosphate uridylyltransferase GalT promotes biofilm formation and enhances UV-B resistance of Bacillus thuringiensis
Ultraviolet radiation (UV) is a major abiotic stress resulting in relative short duration of
Bacillus thuringiensis
(Bt) biopesticides in the field, which is expected to be solved by formation of Bt biofilm with higher UV resistance. Therefore, one of the important prerequisite works is to clarify the functions of biofilm-associated genes on biofilm formation and UV resistance of Bt. In this study, comparative genomics and bioinformatic analysis indicated that BTXL6_19475 gene involved in biofilm formation of Bt XL6 was likely to encode a galactose-1-phosphate uridylyltransferase (GalT, E.C. 2.7.7.12). Heterologous expression of the BTXL6_19475 gene in
Escherichia coli
and detection of its GalT enzyme activity in vitro proved that the gene did encode GalT. Comparing the wild type Bt strain XL6 with
galT
gene knockout mutant Bt XL6ΔgalT and its complementary strain Bt XL6ΔgalT::19,475, GalT promoted the biofilm formation and enhanced the UV-B resistance of Bt XL6 likely by increasing its D-ribose production and reducing its alanine aryldamidase activity. GalT did not affect the growth and the cell motility of Bt XL6. A regulation map had been proposed to elucidate how GalT promoted biofilm formation and enhanced UV-B resistance of Bt XL6 by the cross-talk between Leloir pathway, Embden-Meyerhof glycolysis pathway and pentose phosphate pathway. Our finding provides a theoretical basis for the efficient use of biofilm genes to improve the UV resistance of Bt biofilms and thus extend field duration of Bt formulations based on biofilm engineering.
Journal Article
The natural history of classic galactosemia: lessons from the GalNet registry
Background
Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients.
Methods
Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018.
Results
Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome.
Conclusion
This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Journal Article
The Influence of Nutritional Factors on Immunological Outcomes
Through food intake, humans obtain a variety of nutrients that are essential for growth, cellular function, tissue development, energy, and immune defense. A special interaction between nutrients and gut-associated lymphoid tissue occurs in the intestinal tract. Enterocytes of the intestinal barrier act as sensors for antigens from nutrients and the intestinal microbiota, which they deliver to the underlying immune system of the lamina propria, triggering an immune response. Studies investigating the mechanism of influence of nutrition on immunological outcomes have highlighted an important role of macronutrients (proteins, carbohydrates, fatty acids) and micronutrients (vitamins, minerals, phytochemicals, antioxidants, probiotics) in modulating immune homeostasis. Nutrients exert their role in innate immunity and inflammation by regulating the expression of TLRs, pro- and anti-inflammatory cytokines, thus interfering with immune cell crosstalk and signaling. Chemical substrates derived from nutrient metabolism may act as cofactors or blockers of enzymatic activity, influencing molecular pathways and chemical reactions associated with microbial killing, inflammation, and oxidative stress. Immune cell function appears to be influenced by certain nutrients that form parts of the cell membrane structure and are involved in energy production and prevention of cytotoxicity. Nutrients also contribute to the initiation and regulation of adaptive immune responses by modulating B and T lymphocyte differentiation, proliferation and activation, and antibody production. The purpose of this review is to present the available data from the field of nutritional immunology to elucidate the complex and dynamic relationship between nutrients and the immune system, the delineation of which will lead to optimized nutritional regimens for disease prevention and patient care.
Journal Article
Single-cell transcriptomics reveals mechanisms of Galt gene editing–induced liver injury involving HGF–VEGF–mediated intercellular signaling in mice
Galactosemia, a genetic disorder caused by mutations in the human GALT gene, often leads to multi-organ damage, with liver injury being particularly prominent. To elucidate the molecular mechanisms of Galt in liver injury, this study employed the CRISPR/Cas9 system to construct a Galt (c.847 + 1G > T) gene-edited mouse (GAL mouse) model. Quantitative Real-time PCR and Western blotting revealed a significant reduction of Galt gene in GAL mice. Elevated liver index, serum ALT and AST levels, and H&E staining results indicated significant hepatocyte edema in GAL mice, suggesting a pronounced liver injury phenotype. Single-cell transcriptomics further unveiled significant changes in hepatocyte subtype proportions, with downregulation of metabolism-related genes and upregulation of immune-related genes. Cell communication analysis demonstrated that the communication of HGF and VEGF signaling pathways was significantly enhanced following Galt gene editing. The enhancement of HGF and VEGF signaling pathways may lead to hepatocyte edema, thereby causing liver injury. The GAL mouse model constructed in this study not only revealed the crucial roles of the Galt gene in liver metabolism, immune regulation, and cell communication, but also provided new insights into the pathogenesis of galactosemia and potential therapeutic targets.
Journal Article
integrin α₄β₇ forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1
Both activated and resting CD4⁺ T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin α₄β₇ (α₄β₇), the gut mucosal homing receptor. We find that α₄β₇high CD4⁺ T cells are more susceptible to productive infection than are α₄β₇low⁻neg CD4⁺ T cells in part because this cellular subset is enriched with metabolically active CD4⁺ T cells. α₄β₇high CD4⁺ T cells are CCR5high and CXCR4low; on these cells, α₄β₇ appears in a complex with CD4. The specific affinity of gp120 for α₄β₇ provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.
Journal Article
Gut Immune System and the Implications of Oral-Administered Immunoprophylaxis in Finfish Aquaculture
The gastrointestinal immune system plays an important role in immune homeostasis regulation. It regulates the symbiotic host-microbiome interactions by training and developing the host’s innate and adaptive immunity. This interaction plays a vital role in host defence mechanisms and at the same time, balancing the endogenous perturbations of the host immune homeostasis. The fish gastrointestinal immune system is armed with intricate diffused gut-associated lymphoid tissues (GALTs) that establish tolerance toward the enormous commensal gut microbiome while preserving immune responses against the intrusion of enteric pathogens. A comprehensive understanding of the intestinal immune system is a prerequisite for developing an oral vaccine and immunostimulants in aquaculture, particularly in cultured fish species. In this review, we outline the remarkable features of gut immunity and the essential components of gut-associated lymphoid tissue. The mechanistic principles underlying the antigen absorption and uptake through the intestinal epithelial, and the subsequent immune activation through a series of molecular events are reviewed. The emphasis is on the significance of gut immunity in oral administration of immunoprophylactics, and the different potential adjuvants that circumvent intestinal immune tolerance. Comprehension of the intestinal immune system is pivotal for developing effective fish vaccines that can be delivered orally, which is less labour-intensive and could improve fish health and facilitate disease management in the aquaculture industry.
Journal Article