Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis

BACKGROUND AND AIM: Hepatocyte apoptosis or necrosis from accumulation of bile salts may play an important role in the disease progression of primary sclerosing cholangitis (PSC). The aim of the current study was to measure serum markers of hepatocyte apoptosis (cytokeratin-18 fragments--K18) and necrosis (high-mobility group protein B1--HMGB1) in adults with PSC and examine the relationship with disease severity. METHODS: We measured serum levels of K18 and HMGB1 in well-phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was assessed biochemically, histologically, and PSC Mayo risk score. Quantification of hepatocyte apoptosis was performed using TUNEL assay. RESULTS: The mean age of the study cohort was 49.7 ± 13.3 years and comprised of 67% men and 93% Caucasian. Serum K18 levels were significantly higher in the PSC patients compared to control (217.4 ± 78.1 vs. 157.0 ± 58.2 U/L, p = 0.001). However, HMGB1 levels were not different between the two groups (5.38 ± 2.99 vs. 6.28 ± 2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total bilirubin (r = 0.61, p ≤ 0.001), and albumin (r = -0.4, p = 0.02). Serum K18 levels also correlated with the level of apoptosis present on the liver biopsy (r = 0.8, p ≤ 0.001) and Mayo risk score (r = 0.4, p = 0.015). CONCLUSION: Serum K18 but not HMGB1 levels were increased in PSC and associated with severity of underlying liver disease and the degree of hepatocyte apoptosis

Electrically pumped continuous-wave III–V quantum dot lasers on silicon

Reliable, efficient electrically pumped silicon-based lasers would enable full integration of photonic and electronic circuits, but have previously only been realized by wafer bonding. Here, we demonstrate continuous-wave InAs/GaAs quantum dot lasers directly grown on silicon substrates with a low threshold current density of 62.5 A cm–2, a room-temperature output power exceeding 105 mW and operation up to 120 °C. Over 3,100 h of continuous-wave operating data have been collected, giving an extrapolated mean time to failure of over 100,158 h. The realization of high-performance quantum dot lasers on silicon is due to the achievement of a low density of threading dislocations on the order of 105 cm−2 in the III–V epilayers by combining a nucleation layer and dislocation filter layers with in situ thermal annealing. These results are a major advance towards reliable and cost-effective silicon-based photonic–electronic integration

Features of Idebenone and Related Short-Chain Quinones that Rescue ATP Levels under Conditions of Impaired Mitochondrial Complex I

Short-chain quinones have been investigated as therapeutic molecules due to their ability to modulate cellular redox reactions, mitochondrial electron transfer and oxidative stress, which are pathologically altered in many mitochondrial and neuromuscular disorders. Recently, we and others described that certain short-chain quinones are able to bypass a deficiency in complex I by shuttling electrons directly from the cytoplasm to complex III of the mitochondrial respiratory chain to produce ATP. Although this energy rescue activity is highly interesting for the therapy of disorders associated with complex I dysfunction, no structure-activity-relationship has been reported for short-chain quinones so far. Using a panel of 70 quinones, we observed that the capacity for this cellular energy rescue as well as their effect on lipid peroxidation was influenced more by the physicochemical properties (in particular logD) of the whole molecule than the quinone moiety itself. Thus, the observed correlations allow us to explain the differential biological activities and therapeutic potential of short-chain quinones for the therapy of disorders associated with mitochondrial complex I dysfunction and/or oxidative stress

Neuromarketing and consumer neuroscience:contributions to neurology

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience.Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research.Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology:. First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained.Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing

Survey on open peer review: Attitudes and experience amongst editors, authors and reviewers.

Open peer review (OPR) is a cornerstone of the emergent Open Science agenda. Yet to date no large-scale survey of attitudes towards OPR amongst academic editors, authors, reviewers and publishers has been undertaken. This paper presents the findings of an online survey, conducted for the OpenAIRE2020 project during September and October 2016, that sought to bridge this information gap in order to aid the development of appropriate OPR approaches by providing evidence about attitudes towards and levels of experience with OPR. The results of this cross-disciplinary survey, which received 3,062 full responses, show the majority (60.3%) of respondents to be believe that OPR as a general concept should be mainstream scholarly practice (although attitudes to individual traits varied, and open identities peer review was not generally favoured). Respondents were also in favour of other areas of Open Science, like Open Access (88.2%) and Open Data (80.3%). Among respondents we observed high levels of experience with OPR, with three out of four (76.2%) reporting having taken part in an OPR process as author, reviewer or editor. There were also high levels of support for most of the traits of OPR, particularly open interaction, open reports and final-version commenting. Respondents were against opening reviewer identities to authors, however, with more than half believing it would make peer review worse. Overall satisfaction with the peer review system used by scholarly journals seems to strongly vary across disciplines. Taken together, these findings are very encouraging for OPR's prospects for moving mainstream but indicate that due care must be taken to avoid a "one-size fits all" solution and to tailor such systems to differing (especially disciplinary) contexts. OPR is an evolving phenomenon and hence future studies are to be encouraged, especially to further explore differences between disciplines and monitor the evolution of attitudes

Attitudes and experience amongst editors, authors and reviewers

This work was funded by the European Commission H2020 project OpenAIRE2020 (Grant agreement: 643410, Call: H2020-EINFRA-2014-1). The funder provided support in the form of salaries for authors [TRH, AD, BS], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the `author contributions' section. Please note that the author contributions as listed in the paper are incomplete, owing to a data entry error. The correct information regarding contributions is as follows: - Tony Ross-Hellauer (ORCID 0000-0003-4470-7027): Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project Administration, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing - Arvid Deppe (ORCID 0000-0001-7190-9535): Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Writing – review & editing - Birgit Schmidt (ORCID 0000-0001-8036-5859): Conceptualization, Data curation, Formal analysis, Funding acquisition, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing Competing interests: This work was conducted as part of the OpenAIRE2020 project, an EC-funded initiative to implement and monitor Open Access and Open Science policies in Europe and beyond. The lead author recently joined Know-Center GmbH, Graz, Austria. The Know-Center is funded within the Austrian COMET program – Competence Centers for Excellent Technologies - under the auspices of the Austrian Federal Ministry of Transport, Innovation and Technology, the Austrian Federal Ministry of Economy, Family and Youth, and the State of Styria. COMET is managed by the Austrian Research Promotion Agency FFG. This new commercial affiliation does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.European Commission H2020 - OpenAIRE2020 - Open Access Infrastructure for Research in Europe 2020 (Grant agreement: 643410

OpenAIRE Open Peer Review Survey 2016

This data set contains: - Full data files of a 2016 survey of attitudes to Open Peer Review in xls and csv formats - Survey questions (pdf) - Readme file (txt) Between 8 September and 7 October 2016, OpenAIRE held a survey designed to aid the development of appropriate OPR approaches by providing evidence about the attitudes of authors, editors and reviewers towards OPR, their reservations and needs, as well as to gauging current levels of experience and reservation with different types of OPR. A supplementary aim was to collect feedback on a provisional definition of OPR as created during another strand of work. The survey aimed to aid the development of appropriate OPR approaches by providing evidence about the attitudes of authors, editors and reviewers towards OPR, their reservations and needs, as well as to gauge current levels of experience and reservations with different types of OPR. The survey was conducted via an openly accessible online questionnaire (using the scientific survey platform SoSci, www.soscisurvey.de). It received a total of 3062 complete responses (a further 635 responses were discarded as incomplete). The survey was open to all wishing to take part and distributed via social media, scholarly communications mailing lists, publisher newsletters and, in one case, a publisher internal mailing list (Copernicus Publications). Acknowledgement: This work is funded by the European Commission H2020 project OpenAIRE2020 (Grant agreement: 643410, Call: H2020-EINFRA-2014-1) Contact: Dr Tony Ross-Hellauer, University of Göttingen, State and University Library, [email protected]

Contingency table of attitudes to open access to publications vs. OPR.

<p>Contingency table of attitudes to open access to publications vs. OPR.</p

Views on OPR by scientific discipline.

<p>Views on OPR by scientific discipline.</p

General attitudes towards aspects of open science.

<p>General attitudes towards aspects of open science.</p