Demokratia Josiah Ober, Charles Hedrick / Josiah Ober, Charles Hedrick
2021, 1996, 2021-03-09
eBook
This book is the result of a long and fruitful conversation among practitioners of two very different fields: ancient history and political theory. The topic of the conversation is classical Greek ...democracy and its contemporary relevance. The nineteen contributors remain diverse in their political commitments and in their analytic approaches, but all have engaged deeply with Greek texts, with normative and historical concerns, and with each others' arguments. The issues and tensions examined here are basic to both history and political theory: revolution versus stability, freedom and equality, law and popular sovereignty, cultural ideals and social practice. While the authors are sharply critical of many aspects of Athenian society, culture, and government, they are united by a conviction that classical Athenian democracy has once again become a centrally important subject for political debate. The contributors are Benjamin R. Barber, Alan Boegehold, Paul Cartledge, Susan Guettel Cole, W. Robert Connor, Carol Dougherty, J. Peter Euben, Mogens H. Hansen, Victor D. Hanson, Carnes Lord, Philip Brook Manville, Ian Morris, Martin Ostwald, Kurt Raaflaub, Jennifer Tolbert Roberts, Barry S. Strauss, Robert W. Wallace, Sheldon S. Wolin, and Ellen Meiksins Wood.
Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it ...challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.
Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, ...including the ceca. We have carried out deep microbial community profiling of the microbiota in twenty cecal samples via 16S rRNA gene sequences and an in-depth metagenomics analysis of a single cecal microbiota. We recovered 699 phylotypes, over half of which appear to represent previously unknown species. We obtained 648,251 environmental gene tags (EGTs), the majority of which represent new species. These were binned into over two-dozen draft genomes, which included Campylobacter jejuni and Helicobacter pullorum. We found numerous polysaccharide- and oligosaccharide-degrading enzymes encoding within the metagenome, some of which appeared to be part of polysaccharide utilization systems with genetic evidence for the co-ordination of polysaccharide degradation with sugar transport and utilization. The cecal metagenome encodes several fermentation pathways leading to the production of short-chain fatty acids, including some with novel features. We found a dozen uptake hydrogenases encoded in the metagenome and speculate that these provide major hydrogen sinks within this microbial community and might explain the high abundance of several genera within this microbiome, including Campylobacter, Helicobacter and Megamonas.
Animal models of acute lung injury Matute-Bello, Gustavo; Frevert, Charles W; Martin, Thomas R
American journal of physiology. Lung cellular and molecular physiology,
09/2008, Letnik:
295, Številka:
3
Journal Article
Recenzirano
Odprti dostop
1 Medical Research Service of the Veterans Affairs/Puget Sound Health Care System and 2 Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, and 3 ...Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington
ABSTRACT
Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.
acute respiratory distress syndrome; human lung injury
Address for reprint requests and other correspondence: G. Matute-Bello, 815 Mercer St., Seattle, WA 98109
Globally, rising temperatures have resulted in numerous examples of poleward shifts in species distribution patterns with accompanying changes in community structure and ecosystem processes. In the ...Gulf of Mexico, higher mean temperatures and less frequent winter freezes have led to the expansion of tropics-associated marine organisms. Our objectives were to quantify changing environmental conditions and the poleward expansion of the common snook Centropomus undecimalis into the Cedar Keys area of Florida, USA (29 deg N). The snook is an economically and recreationally important sport fish found from southern Brazil to south Florida. Cedar Key and the Lower Suwannee River are north of the snook's historically documented range, likely due to lethal water temperatures during winter. Using data from a long-term monitoring program, we report an increase in catches of snook in this area since 2007. The spatial and temporal expansion of the species began with adult fish in 2007. By 2018, snook of all sizes were found in the region, and we found strong evidence of local reproduction during 2016-2018. The locations of nursery habitat and winter thermal refuges (e.g., freshwater springs) need to be identified and have implications for land-use policy and minimum-flow regulations for rivers. The arrival of the snook in the northern Gulf of Mexico could affect food web ecology and habitat interactions among estuarine predators, and future studies should evaluate snook's food habits and competitive interactions with resident fishes in this expanded range. Our study provides an example of how species range expansions due to changing temperatures should result in new research priorities to evaluate impacts of climate change on coastal systems.
Here, we take a snapshot of the high-throughput sequencing platforms, together with the relevant analytical tools, that are available to microbiologists in 2012, and evaluate the strengths and ...weaknesses of these platforms in obtaining bacterial genome sequences. We also scan the horizon of future possibilities, speculating on how the availability of sequencing that is 'too cheap to metre' might change the face of microbiology forever.
Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total ...25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD.
Adult subjects (n = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio.
Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively "safety parameters") did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3).
ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.
Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (almost ...equal to22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, ...placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (E
) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p < 0.001) lower Drug Liking VAS E
compared with the positive control. Results were consistent for all secondary endpoints in both studies. In both studies, all doses of esmethadone were statistically equivalent to placebo on Drug Liking VAS E
(p < 0.05). In the Ketamine Study, Drug Liking VAS E
scores for esmethadone at all tested doses were significantly lower vs. dextromethorphan (p < 0.05) (exploratory endpoint). These studies indicate no meaningful abuse potential for esmethadone at all tested doses.
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