11 research outputs found

    The Effects of a-Helical Structure and Cyanylated Cysteine on Each Other

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    A systematic investigation of the artificial amino acid cyanylated cysteine in a model helical peptide, to show both the non-perturbing nature of the amino acid and its ability to report on local structure formation. --author-supplied descriptio

    The effect of age and gender on anti-saccade performance: Results from a large cohort of healthy aging individuals

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    By 2050, the global population of people aged 65 years or older will triple. While this is accompanied with an increasing burden of age-associated diseases, it also emphasizes the need to understand the effects of healthy aging on cognitive processes. One such effect is a general slowing of processing speed, which is well documented in many domains. The execution of anti-saccades depends on a well-established brain-wide network ranging from various cortical areas and basal ganglia through the superior colliculus down to the brainstem saccade generators. To clarify the consequences of healthy aging as well as gender on the execution of reflexive and voluntary saccades, we measured a large sample of healthy, non-demented individuals (n = 731, aged 51–84 years) in the anti-saccade task. Age affected various aspects of saccade performance: The number of valid trials decreased with age. Error rate, saccadic reaction times (SRTs), and variability in saccade accuracy increased with age, whereas anti-saccade costs, accuracy, and peak velocity of anti-saccades and direction errors were not affected by age. Gender affected SRTs independent of age and saccade type with male participants having overall shorter SRTs. Our rigid and solid statistical testing using linear mixed-effect models provide evidence for a uniform slowing of processing speed independent of the actually performed eye movement. Our data do not support the assumption of a specific deterioration of frontal lobe functions with aging

    The Age of Decadence

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    This review essay was originally published in Victorian Literature and Culture. The version of record is available at: https://doi.org/10.1017/S1060150322000018. © The Author(s), 2022. Published by Cambridge University Press.What does “decadence” mean? Does it mean anything at all? Is it sinister or irresistibly appealing? Regardless of the ambiguity that surrounds the word “decadence” (often with a small “d”), no one can deny that decadence (frequently with a capital “D,” especially when it alludes to the late nineteenth-century European cultural movement) has been sweeping the world of academic publishing. Seen from the perspective of 2022, the past few years appear to have been, at least among scholars, a decade of decadence. Joseph Bristow opens his chapter on “Female Decadence” for the 2016 volume The History of British Women's Writing, 1880–1920 by saying, “There is no question that by the mid-1890s one word had come to define avant-garde art and literature in Britain,” and that word was decadence. Judging by the recent proliferation of books and art exhibitions on both sides of the Atlantic, history appears to be repeating itself and on a broader scale. Decadence is now defining, or at least preoccupying, many of us

    Netta Syrett’s Afterlife: From London to Hollywood

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    Although the words above, spoken by the actor Katharine Hepburn in A Woman Rebels, were the creation of two male screenwriters – Anthony Veiller (1903-1965), an American, and Ernest Vajda (1886-1954), a Hungarian emigré to America – the source text for this 1936 film was a 1929 novel by a British woman writer. That the novel in question, Portrait of a Rebel, proved popular and successful enough on both sides of the Atlantic to be of interest to RKO Radio Pictures, a Hollywood studio, seems astonishing now. Its author, Netta Syrett, was a member neither of the current generation nor even of the Edwardian or Georgian ones immediately preceding it, for she had been born in 1865 – thus, in the middle of the previous century – and was nearing the end of a long career. Her literary fame had been achieved first in The Yellow Book with her short story ‘Thy Heart’s Desire’ for the July 1894 issue (Volume II), followed by further contributions in October 1895 (Volume VII) and January 1897 (Volume XII). She had, nonetheless, remained both relevant and appealing to a wide swathe of the reading public. Just how she accomplished what so many of her contemporaries did not can only be a matter for speculation. One possibility, however, was through her close attention to expressions of taste communicated via the medium of reviews, as these became more readily available to authors at the turn of the twentieth century thanks to the rise of professional press-cutting services, to which she herself was a subscriber, as evidenced by the collection of materials sent to her by Romeike and Curtice

    Hypersensitivity of BRCA1 heterozygote lymphoblastoid cells to gamma radiation and PARP inhibitors

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    This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Bourton EC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.Vidal Sassoon Foundation of America and “The Balls to Cancer” Charity, Coventry, U

    The Effects of α-Helical Structure and Cyanylated Cysteine on Each Other

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    β-Thiocyanatoalanine, or cyanylated cysteine, is an artificial amino acid that can be introduced at solvent-exposed cysteine residues in proteins via chemical modification. Its facile post-translational synthesis means that it may find broad use in large protein systems as a probe of site-specific structure and dynamics. The CN stretching vibration of this artificial side chain provides an isolated infrared chromophore. To test both the perturbative effect of this side chain on local secondary structure and its sensitivity to structural changes, three variants of a model water-soluble alanine-repeat helix were synthesized containing cyanylated cysteine at different sites. The cyanylated cysteine side chain is shown to destabilize, but not completely disrupt, the helical structure of the folded peptide when substituted for alanine. In addition, the CN stretching bandwidth of the artificial side chain is sensitive to the helix−coil structural transition. These model system results indicate that cyanylated cysteine can be placed into protein sequences with a native helical propensity without destroying the helix, and further that the CN probe may be able to report local helix formation events even when it is water-exposed in both the ordered and disordered conformational states. These results indicate that cyanylated cysteine could be a widely useful probe of structure-forming events in proteins with large in vitro structural distributions

    Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study

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    Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide

    Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial

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    Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. Results: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors
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