1,750 research outputs found
Review of David Adams, Colonial Odysseys: Empire and Epic in the Modernist Novel.
David Adams, Colonial Odysseys: Empire and Epic in the Modernist Novel. Ithaca: Cornell University Press, 2003. 249 pp. (+ xi) ISBN 0801441617 (paper)
Evaluating Historical Paradigms Of Sterility In Perinatal Microbiology And Ramifications For Pregnancy Outcomes
Next-generation sequencing technologies, especially 16S rRNA gene and metagenomic sequencing have allowed investigations of low microbial biomass tissues of the human body. While these sequencing methodologies have provided large amounts of reliable data for higher microbial biomass sites, such as the mouth, intestine, and vagina, tissues of low microbial biomass sites are subject to specific caveats that were not appropriately considered in early investigations of these sites. Low microbial biomass sites of particular interest have included those of the reproductive and urinary systems. Utilization of DNA sequencing methodologies have allowed researchers to challenge existing paradigms of sterility around these sites that were historically considered sterile, including but not limited to the placenta, the endometrium, and the bladder. While a thorough and complete understanding of the microbial signals in urogenital compartments is necessary for the best patient care and treatment, premature conclusions that redefine historical paradigms can have harmful consequences on patient health, especially for pregnant women with whom microorganisms have been associated with multiple adverse pregnancy outcomes.
In this dissertation, I present a lack of evidence for a placental microbiota in humans using multiple modes of microbiological inquiry. Through culture, quantitative real-time PCR (qPCR), 16S rRNA gene sequencing, and metagenomics we found no evidence of bacterial signals beyond those also present in background technical controls. This work with human subjects was subsequently complemented by work in mice, in which we investigated the bacterial signals in the murine placenta and fetus, as well as multiple murine tissue control sites; we again found no consistent evidence of a placental microbiota or in utero colonization through multiple microbiological methodologies. Conversely, investigations of the urine of pregnant women revealed evidence of a low abundance bladder microbiota. We found bacterial signals that clearly exceeded those of technical controls, suggesting that a shift in sterility paradigm for the upper urinary tract may be warranted. Specifically, through bacterial culture, qPCR, and 16S rRNA gene sequencing we found evidence of a bladder microbiota in pregnant women that showed strong variation among individuals and consisted of Ureaplasma urealyticum and Gram-positive anaerobic cocci. A more thorough understanding of the bladder microbiota in pregnant women across gestation will allow healthcare professionals to address urinary and bladder symptoms in a way that alleviates or prevents pregnancy complications.
This body of work provides strategies for the thorough investigation of low microbial biomass sites and demonstrates the high degree of evidence necessary to overturn classic paradigms of sterility in perinatal medicine and host biology in general
Review of Edward P. Comentale, Modernism, Cultural Production, and the British Avant-Garde.
Edward P. Comentale, Modernism, Cultural Production, and the British Avant-Garde. New York and Cambridge: Cambridge University Press, 2004. 261 pp. (+x) ISBN 0521835895
Review of Edward P. Comentale, Modernism, Cultural Production, and the British Avant-Garde.
Edward P. Comentale, Modernism, Cultural Production, and the British Avant-Garde. New York and Cambridge: Cambridge University Press, 2004. 261 pp. (+x) ISBN 0521835895
The Arctic in World Environmental History
For millions of years, the Arctic has been the world\u27s most important barometer of global change and amplifier of global warming. For twenty thousand years, the Arctic has been the homeland of modern human settlement, and it has played a central role in the interplay between global climate change and human migration throughout Eurasia and the Americas. Since the late fifteenth century, Arctic aboriginal peoples, lands, and seas have been thoroughly integrated into the international history of European trade, capitalism, and colonization; the territorial expansion of modern nation states; and the transnational strategic history since the outset of the Cold War, including the continued basing of nuclear-armed missiles, bombers, and submarines throughout the Arctic region.
Appreciation of this international history can provide lessons for contemporary policymakers to help mitigate grave risks to human life and biodiversity in the Arctic and sub-Arctic. For example, this Article calls for negotiations between the U.S., NATO, and the Russian Federation on the basis of Russian President Mikhail Gorbachev\u27s 1987 proposal to transform the Arctic into a zone of peace and, specifically, to establish a nuclear free-zone in northern Europe.
In conclusion, this Article identifies how deeply embedded global systems of political economy and international relations continue to shape recent developments in the Arctic at this time of exacerbated climate change and resulting ecological crisis. Appreciation of the Arctic\u27s environmental history can help decision-makers to more knowledgeably and effectively support indigenous self-determination, resource conservation, and environmental stewardship throughout the circumpolar bioregion
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Modeling Intracerebral Hemorrhage Growth and Response to Anticoagulation
The mechanism for hemorrhage enlargement in the brain, a key determinant of patient outcome following hemorrhagic stroke, is unknown. We performed computer-based stochastic simulation of one proposed mechanism, in which hemorrhages grow in “domino” fashion via secondary shearing of neighboring vessel segments. Hemorrhages were simulated by creating an initial site of primary bleeding and an associated risk of secondary rupture at adjacent sites that decayed over time. Under particular combinations of parameters for likelihood of secondary rupture and time-dependent decay, a subset of lesions expanded, creating a bimodal distribution of microbleeds and macrobleeds. Systematic variation of the model to simulate anticoagulation yielded increases in both macrobleed occurrence (26.9%, 53.2%, and 70.0% of all hemorrhagic events under conditions simulating no, low-level, and high-level anticoagulation) and final hemorrhage size (median volumes 111, 276, and 412 under the same three conditions), consistent with data from patients with anticoagulant-related brain hemorrhages. Reversal from simulated high-level anticoagulation to normal coagulation was able to reduce final hemorrhage size only if applied relatively early in the course of hemorrhage expansion. These findings suggest that a model based on a secondary shearing mechanism can account for some of the clinically observed properties of intracerebral hemorrhage, including the bimodal distribution of volumes and the enhanced hemorrhage growth seen with anticoagulation. Future iterations of this model may be useful for elucidating the effects of hemorrhage growth of factors related to secondary shearing (such as small vessel pathology) or time-dependent decay (such as hemostatic agents)
ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition
SummaryResolution of DNA double-strand breaks (DSBs) is essential for the suppression of genome instability. DSB repair in transcriptionally active genomic regions represents a unique challenge that is associated with ataxia telangiectasia mutated (ATM) kinase-mediated transcriptional silencing. Despite emerging insights into the underlying mechanisms, how DSB silencing connects to DNA repair remains undefined. We observe that silencing within the rDNA depends on persistent DSBs. Non-homologous end-joining was the predominant mode of DSB repair allowing transcription to resume. ATM-dependent rDNA silencing in the presence of persistent DSBs led to the large-scale reorganization of nucleolar architecture, with movement of damaged chromatin to nucleolar cap regions. These findings identify ATM-dependent temporal and spatial control of DNA repair and provide insights into how communication between DSB signaling and ongoing transcription promotes genome integrity
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