489 research outputs found
Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase
No full texteEF2K [eEF2 (eukaryotic elongation factor 2) kinase] phosphorylates and inactivates the translation elongation factor eEF2. eEF2K is not a member of the main eukaryotic protein kinase superfamily, but instead belongs to a small group of so-called ?-kinases. The activity of eEF2K is normally dependent upon Ca2+ and calmodulin. eEF2K has previously been shown to undergo autophosphorylation, the stoichiometry of which suggested the existence of multiple sites. In the present study we have identified several autophosphorylation sites, including Thr348, Thr353, Ser366 and Ser445, all of which are highly conserved among vertebrate eEF2Ks. We also identified a number of other sites, including Ser78, a known site of phosphorylation, and others, some of which are less well conserved. None of the sites lies in the catalytic domain, but three affect eEF2K activity. Mutation of Ser78, Thr348 and Ser366 to a non-phosphorylatable alanine residue decreased eEF2K activity. Phosphorylation of Thr348 was detected by immunoblotting after transfecting wild-type eEF2K into HEK (human embryonic kidney)-293 cells, but not after transfection with a kinase-inactive construct, confirming that this is indeed a site of autophosphorylation. Thr348 appears to be constitutively autophosphorylated in vitro. Interestingly, other recent data suggest that the corresponding residue in other ?-kinases is also autophosphorylated and contributes to the activation of these enzymes [Crawley, Gharaei, Ye, Yang, Raveh, London, Schueler-Furman, Jia and Cote (2011) J. Biol. Chem. 286, 2607-2616]. Ser366 phosphorylation was also detected in intact cells, but was still observed in the kinase-inactive construct, demonstrating that this site is phosphorylated not only autocatalytically but also in trans by other kinases
NifH-Harboring Bacterial Community Composition across an Alaskan Permafrost Thaw Gradient
No full textabstract: Since nitrogen (N) is often limiting in permafrost soils, we investigated the N[subscript 2]-fixing genetic potential and the inferred taxa harboring those genes by sequencing nifH gene fragments in samples taken along a permafrost thaw gradient in an Alaskan boreal soil. Samples from minimally, moderately and extensively thawed sites were taken to a depth of 79 cm to encompass zones above and below the depth of the water table. NifH reads were translated with frameshift correction and 112,476 sequences were clustered at 5% amino acid dissimilarity resulting in 1,631 OTUs. Sample depth in relation to water table depth was correlated to differences in the NifH sequence classes with those most closely related to group I nifH-harboring Alpha- and Beta-Proteobacteria in higher abundance above water table depth while those related to group III nifH-harboring Delta Proteobacteria more abundant below. The most dominant below water table depth NifH sequences, comprising 1/3 of the total, were distantly related to Verrucomicrobia-Opitutaceae. Overall, these results suggest that permafrost thaw alters the class-level composition of N[subscript 2]-fixing communities in the thawed soil layers and that this distinction corresponds to the depth of the water table. These nifH data were also compared to nifH sequences obtained from a study at an Alaskan taiga site, and to those of other geographically distant, non-permafrost sites. The two Alaska sites were differentiated largely by changes in relative abundances of the same OTUs, whereas the non-Alaska sites were differentiated by the lack of many Alaskan OTUs, and the presence of unique halophilic, sulfate- and iron-reducing taxa in the Alaska sites.View the article as published at http://journal.frontiersin.org/article/10.3389/fmicb.2016.01894/ful
Comparative metagenomics reveals impact of contaminants on groundwater microbiomes
No full textabstract: To understand patterns of geochemical cycling in pristine versus contaminated groundwater ecosystems, pristine shallow groundwater (FW301) and contaminated groundwater (FW106) samples from the Oak Ridge Integrated Field Research Center (OR-IFRC) were sequenced and compared to each other to determine phylogenetic and metabolic difference between the communities. Proteobacteria (e.g., Burkholderia, Pseudomonas) are the most abundant lineages in the pristine community, though a significant proportion ( >55%) of the community is composed of poorly characterized low abundance (individually <1%) lineages. The phylogenetic diversity of the pristine community contributed to a broader diversity of metabolic networks than the contaminated community. In addition, the pristine community encodes redundant and mostly complete geochemical cycles distributed over multiple lineages and appears capable of a wide range of metabolic activities. In contrast, many geochemical cycles in the contaminated community appear truncated or minimized due to decreased biodiversity and dominance by Rhodanobacter populations capable of surviving the combination of stresses at the site. These results indicate that the pristine site contains more robust and encodes more functional redundancy than the stressed community, which contributes to more efficient nutrient cycling and adaptability than the stressed community.View the article as published at http://journal.frontiersin.org/article/10.3389/fmicb.2015.01205/ful
Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area
No full textabstract: Background
HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies.
Methods
This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis.
Results
Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3–96.5) and 66.7% (34.9–90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7–95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4–92.9) and 80.0% (67.3–88.8) of all 60 TB cases.
Conclusions
Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0952-
The Role of Foreign Direct Investment in East Asian Economic Development, NBER-EASE Volume 9
No full textSarah Fielding: Satire and Subversion in the Eighteenth-Century Novel
No full textThis study of Sarah Fielding (1710―68) is an original contribution to Fielding scholarship that has a dual purpose: to support those who are striving to re-introduce her to the modern literary landscape in an effort to restore her eighteenth-century literary standing, and to firmly establish Fielding as an early feminist writer. It is argued here that throughout her oeuvre Fielding challenged prevailing traditions that denied women a choice, particularly in education, employment and marriage. These themes are also considered in the political treatises of Mary Astell (1666―1731) and Mary Wollstonecraft (1759―97), who are now widely recognised as feminist writers.
It is further argued that Fielding’s subversion in fiction of the English patriarchal system is underscored by her unorthodox performance in the literary arena. This is fully explored alongside her use of sentimentalism as a literary tool with which she challenges her seemingly inhumane society. Fielding’s interest in ‘the Labyrinths of the Mind’ (in modern terms, human psychology) will also be addressed as will her placement in the history of feminism and her placement in the sentimental novel tradition. Fielding’s performance as a literary critic will be compared with the few female authors who, like her, dared to publish literary criticism during her writing career. Accordingly, extracts from Fielding’s novels and her two critical pamphlets will be thoroughly examined.
An updated biography of Fielding that is also included here will provide evidence for a further claim, that her fiction is autobiographical in part. A comprehensive account of Fielding’s performance as a literary critic forms the final chapter of this work. It is the first full-length examination of her contribution to the genre and includes an appraisal of her recently unearthed critical pamphlet entitled A Comparison Between the Horace of Corneille and The Roman Father of Mr. Whitehead (1750) that is yet to be formerly attributed to her. Ultimately this study of Fielding will go far beyond what has previously been written about this remarkable eighteenth-century author, particularly regarding her feminist activity
Forward-scatter and side-scatter dataset for epithelial cells from touch samples analyzed by flow cytometry
No full textAbstract‘Touch’ or trace biological samples submitted to caseworking labs as evidence often contain biological material from multiple individuals which can result in mixed DNA profiles. These mixture profiles are difficult to interpret and may cause analytical bottlenecks for forensic laboratories. The data in this brief reports the variation in the relative abundance of intact epithelial cells deposited by four different donors across nine days. Touch samples were generated each day by rubbing a polypropylene tube with both hands for five minutes. Forward-scatter area (FSC-A) and side-scatter area (SSC-A) data was acquired with the BD FACSCanto™ II Analyzer. The relative abundance of different sub-populations within the FSC-A and SSC-A plots was calculated against the total number of events analyzed in each sample. Mean and standard deviation values were calculated for each donor
Private devotion in England on the eve of the Reformation illustrated from works printed or reprinted in the period 1530-40
No full textThis is the first attempt to provide a detailed description of the different types of devotional literature (excluding all liturgical books, biblical translations, doctrinal and polemic works, saintS lives and sermons) available in print to English readers in the years immediately preceding England's break with Rome. It shows that there were far more Catholic works of devotion, many of them written or printed for the first time 1520 - 35, than has previously been recognized. It is also clear that this flourishing literature came to a sudden and decisive end in 1535, although the tradition lived on unofficially to be taken up by the English Recusants. The leading themes of this traditional literature are indicated in chapters on treatises about confession and prayer, the mass, the life and Passion of Christ, on tribulation, death and the Last Things, while more general teaching about the Christian life addressed to religious, contemplatives and lay people, and the humanist and Protestant contribution to this literature is also discussed. The treatises are doctrinally sound and on the whole advocate moderation and common-sense; they avoid many of the weaknesses of popular non-literary devotion, including the Marioleatry and excessive morbidity for which the late middle ages are often condemned. Some of the weaknesses of the Catholic tradition are suggested by comparison with the more rational and secular attitudes of Christian humanist , authors, notably Erasmus, available during the 1530s. The Protestants, whose treatises become increasingly common, despite official censorship, during the decade until they dominate its second half, carry the humanist~ reform much further, and break with the Catholic Church. Traditional devotional topics and audiences are displaced by doctrinal and biblical teaching addressed to lay people. The Bible replaces the Church's authority and there is more emphasis on the spiritual and social dimensions of religion
The geographic diversity of authorship in leading general surgery journals; A study of 24,332 authors
No full textBackground: Research guides evidence-based general surgery practice, advocacy, policy and resource allocation, but is seemingly lacking representation from those countries with greatest disease burden and mortality. Accordingly, we conducted a geographic study of publications in the most impactful general surgery journals worldwide. Methods: The six general surgery journals with the highest 2020 impact factors were selected. Only journals specific to general surgery were included. For all original articles over the past five years, the affiliated country and city were extracted for the first, second and last author. Number of publications were adjusted per capita, and compared to Human Development Index (HDI) using logistic regression. Results: 8274 original articles were published in the top six ranked general surgery journals over 2016e2020, with 24,332 affiliated authors. Authors were most commonly associated with the US (27.88%), Japan (9.09%) and China (8.46%), or per capita, The Netherlands, Sweden and Singapore. There is a linear association between publishing in a top six journal and HDI of country of affiliation. Just four publications were from medium or low HDI countries over the period. Conclusion: Authorship in leading general surgery journals is predominantly from wealthy, Western countries. Authorship is associated with affiliation with a high HDI country, with few authors from medium or low HDI countries. There is a lack of representation in literature from Africa, Russia, and parts of Southeast Asia, and thus a lack of locally relevant evidence to guide surgical practice in these areas of high disease burden and low life expectancy.Jed O. Campbell, Aashray K. Gupta, Amy Lu, Ye Fang Lim, Neel Mishra, Joseph N. Hewitt, Christopher D. Ovenden, Joshua G. Kovoor, Stephen Bacchi, Markus Trochsler, Adam Well
National Trends in Racial and Ethnic Disparities in Mortality from Mechanical Complications of Cardiac Valves and Grafts (1999–2020)
No full textBackground: The volume of cardiac valve and coronary artery revascularization procedures is rising in the United States. This cross-sectional study explores ethnic disparities in mortality in cardiac surgery attributed to mechanical failures of implantable heart valves and coronary artery grafts. Methods: We used the CDC Wide-Ranging Online Data for Epidemiologic Research Multiple Causes of Death database to identify patients whose single cause of death was categorized by complications of cardiovascular prosthetic devices, implants, and grafts (ICD-10 code T82) between 1999 and 2020. The Joinpoint software (version 5.2.0, National Cancer Institute) was used to construct log-linear regression models to estimate the average annual percent changes in age-adjusted mortality (per 100,000). These patterns were compared and stratified by sex, age (0–44, 44–64, and 65 years or older), and US census regions between White, Black, Hispanic, non-Hispanic, American Indian, Alaskan Native, Asian American, and Pacific Islanders. Results: Age-adjusted mortality due to mechanical failures of cardiac implants and grafts declined across ethnicities from 2.21 (95% CI 2.16–2.27) in 1999 to 0.88 (95% CI 0.85–0.91) in 2020. Black populations (1.31 [95% CI 1.20–1.42]), both men (1.56 [95% CI 1.37–1.74]) and women (1.02 [95% CI 0.90–1.15]) experienced higher mortality in 2020 compared to all other ethnicities. This disparity was pronounced in younger groups (age 0–64), wherein age-adjusted mortality among Black populations (0.18 [95% CI 0.13–0.25]) more than doubled that of White populations (0.08 [95% CI 0.06–0.10]). Conclusions: Over the last two decades, age-adjusted mortality due to mechanical complications of cardiovascular implants has declined significantly. However, Black men and women, particularly younger patients, continue to experience higher death rates compared to other ethnicities
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