A wide-ranging study that illuminates the connection between epidemic diseases and societal change, from the Black Death to Ebola This sweeping exploration of the impact of epidemic diseases looks at ...how mass infectious outbreaks have shaped society, from the Black Death to today. In a clear and accessible style, Frank M. Snowden reveals the ways that diseases have not only influenced medical science and public health, but also transformed the arts, religion, intellectual history, and warfare. A multidisciplinary and comparative investigation of the medical and social history of the major epidemics, this volume touches on themes such as the evolution of medical therapy, plague literature, poverty, the environment, and mass hysteria. In addition to providing historical perspective on diseases such as smallpox, cholera, and tuberculosis, Snowden examines the fallout from recent epidemics such as HIV/AIDS, SARS, and Ebola and the question of the world's preparedness for the next generation of diseases.
Informal entrepreneurship (IE) has received increased recognition because of its theoretical distinctiveness and practical relevance. However, the burgeoning literature on IE is difficult to ...navigate, due to its rapid growth across different disciplines. Through an integrative review, we introduce a novel typology of informal entrepreneurs that captures their heterogeneity across various contexts. We point out a dynamic perspective of IE, consisting of three pathways—the reactive formalizing, the proactive formalizing, and the informalizing pathways—along which informal entrepreneurs move, acquiring or foregoing regulative legitimacy. Our review extends the theory on IE, outlines promising research avenues, and suggests relevant practical implications.
At the outset of the twentieth century, malaria was Italy's major public health problem. It was the cause of low productivity, poverty, and economic backwardness, while it also stunted literacy, ...limited political participation, and undermined the army. In this book Frank Snowden recounts how Italy became the world center for the development of malariology as a medical discipline and launched the first national campaign to eradicate the disease.
Snowden traces the early advances, the setbacks of world wars and Fascist dictatorship, and the final victory against malaria after World War II. He shows how the medical and teaching professions helped educate people in their own self-defense and in the process expanded trade unionism, women's consciousness, and civil liberties. He also discusses the antimalarial effort under Mussolini's regime and reveals the shocking details of the German army's intentional release of malaria among Italian civilians-the first and only known example of bioterror in twentieth-century Europe. Comprehensive and enlightening, this history offers important lessons for today's global malaria emergency.
Renal tumors comprise ~7% of all malignant pediatric tumors. Approximately 90% of pediatric kidney tumors comprise Wilms tumors, and the remaining 10% include clear cell sarcoma of the kidney, ...malignant rhabdoid tumor of the kidney, renal cell carcinoma and other rare renal tumors. Over the last 30 years, the role of cytokines and their receptors has been considerably investigated in both cancer progression and anti-cancer therapy. However, more effective immunotherapies require the cytokine profiling of each tumor type and comprehensive understanding of tumor biology. In this study, we aimed to investigate the activation of signaling pathways in response to cytokines in three pediatric kidney tumor cell lines, in WT-CLS1 and WT-3ab cells (both are Wilms tumors), and in G-401 cells (a rhabdoid kidney tumor, formerly classified as Wilms tumor). We observed that interferon-alpha (IFN-α) and interferon-gamma (IFN-γ) very strongly induced the activation of the STAT1 protein, whereas IL-6 and IFN-α activated STAT3 and IL-4 activated STAT6 in all examined tumor cell lines. STAT protein activation was examined by flow cytometry and Western blot using phospho-specific anti-STAT antibodies which recognize only activated (phosphorylated) STAT proteins. Nuclear translocation of phospho-STAT proteins upon activation with specific cytokines was furthermore confirmed by immunofluorescence. Our results also showed that both IFN-α and IFN-γ caused upregulation of major histocompatibility complex (MHC) class I proteins, however, these cytokines did not have any effect on the expression of MHC class II proteins. We also observed that pediatric kidney tumor cell lines exhibit the functional expression of an additional cytokine signaling pathway, the tumor necrosis factor (TNF)-α-mediated activation of nuclear factor kappa B (NF-κB). In summary, our data show that human pediatric renal tumor cell lines are responsive to stimulation with various human cytokines and could be used as in vitro models for profiling cytokine signaling pathways.
The Tethys Ocean was compartmentalized into the Mediterranean Sea and Indian Ocean during the early Miocene, yet the exact nature and timing of this disconnection are not well understood. Here we ...present two new neodymium isotope records from isolated carbonate platforms on both sides of the closing seaway, Malta (outcrop sampling) and the Maldives (IODP Site U1468), to constrain the evolution of past water mass exchange between the present day Mediterranean Sea and Indian Ocean via the Mesopotamian Seaway. Combining these data with box modeling results indicates that water mass exchange was reduced by ~90% in a first step at ca. 20 Ma. The terminal closure of the seaway then coincided with the sea level drop caused by the onset of permanent glaciation of Antarctica at ca. 13.8 Ma. The termination of meridional water mass exchange through the Tethyan Seaway resulted in a global reorganization of currents, paved the way to the development of upwelling in the Arabian Sea and possibly led to a strengthening of South Asian Monsoon.
The concentration and isotope composition of molybdenum (Mo) in sediments and sedimentary rocks are widely used proxies for anoxic conditions in the water column of paleo-marine systems. While the ...mechanisms leading to Mo fixation in modern restricted basins with anoxic and sulfidic (euxinic) conditions are reasonably well constrained, few studies have focused on Mo cycling in the context of open-marine anoxia. Here we present Mo data for water column particulate matter, modern surface sediments and a paleo-record covering the last 140,000years from the Peruvian continental margin. Mo concentrations in late Holocene and Eemian (penultimate interglacial) shelf sediments off Peru range from ∼70 to 100µgg−1, an extent of Mo enrichment that is thought to be indicative of (and limited to) euxinic systems. To investigate if this putative anomaly could be related to the occasional occurrence of sulfidic conditions in the water column overlying the Peruvian shelf, we compared trace metal (Mo, vanadium, uranium) enrichments in particulate matter from oxic, nitrate-reducing (nitrogenous) and sulfidic water masses. Coincident enrichments of iron (Fe) (oxyhydr)oxides and Mo in the nitrogenous water column as well as co-variation of dissolved Fe and Mo in the sediment pore water suggest that Mo is delivered to the sediment surface by Fe (oxyhydr)oxides. Most of these precipitate in the anoxic-nitrogenous water column due to oxidation of sediment-derived dissolved Fe with nitrate as a terminal electron acceptor. Upon reductive dissolution in the surface sediment, a fraction of the Fe and Mo is re-precipitated through interaction with pore water sulfide. The Fe- and nitrate-dependent mechanism of Mo accumulation proposed here is supported by the sedimentary Mo isotope composition, which is consistent with Mo adsorption onto Fe (oxyhydr)oxides. Trace metal co-variation patterns as well as Mo and nitrogen isotope systematics suggest that the same mechanism of Mo delivery caused the ‘anomalously’ high interglacial Mo accumulation rates in the paleo-record. Our findings suggest that Fe- and nitrate-dependent Mo shuttling under nitrogenous conditions needs to be considered a possible reason for sedimentary Mo enrichments during past periods of widespread anoxia in the open ocean.
Epitaxial growth of SrTiO₃ on silicon by molecular beam epitaxy has opened up the route to the integration of functional complex oxides on a silicon platform. Chief among them is ferroelectric ...functionality using perovskite oxides such as BaTiO₃. However, it has remained a challenge to achieve ferroelectricity in epitaxial BaTiO₃ films with a polarization pointing perpendicular to the silicon substrate without a conducting bottom electrode. Here, we demonstrate ferroelectricity in such stacks. Synchrotron X-ray diffraction and high-resolution scanning transmission electron microscopy reveal the presence of crystalline domains with the long axis of the tetragonal structure oriented perpendicular to the substrate. Using piezoforce microscopy, polar domains can be written and read and are reversibly switched with a phase change of 180°. Open, saturated hysteresis loops are recorded. Thus, ferroelectric switching of 8- to 40-nm-thick BaTiO₃ films in metal-ferroelectric-semiconductor structures is realized, and field-effect devices using this epitaxial oxide stack can be envisaged.
SUMMARY
Chloroplasts possess a considerably reduced genome that is decoded via an almost minimal set of tRNAs. These features make an excellent platform for gaining insights into fundamental ...mechanisms that govern protein expression. Here, we present a comprehensive and revised perspective of the mechanisms that drive codon selection in the chloroplast of Chlamydomonas reinhardtii and the functional consequences for protein expression. In order to extract this information, we applied several codon usage descriptors to genes with different expression levels. We show that highly expressed genes strongly favor translationally optimal codons, while genes with lower functional importance are rather affected by directional mutational bias. We demonstrate that codon optimality can be deduced from codon–anticodon pairing affinity and, for a small number of amino acids (leucine, arginine, serine, and isoleucine), tRNA concentrations. Finally, we review, analyze, and expand on the impact of codon usage on protein yield, secondary structures of mRNA, translation initiation and termination, and amino acid composition of proteins, as well as cotranslational protein folding. The comprehensive analysis of codon choice provides crucial insights into heterologous gene expression in the chloroplast of C. reinhardtii, which may also be applicable to other chloroplast‐containing organisms and bacteria.
Significance Statement
This work provides new insights into codon usage bias in chloroplasts. It is crucial for codon optimization of heterologous genes and to understand gene regulation in chloroplasts.
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