Extracellular Vesicles from Cod (<i>Gadus morhua</i> L.) Mucus contain Innate Immune Factors and Deiminated Protein Cargo

Extracellular vesicles are released from cells and participate in cell communication via transfer of protein and genetic cargo derived from the parent cells. EVs play roles in normal physiology and immunity and are also linked to various pathological processes. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes with physiological and pathophysiological roles. PADs cause post-translational protein deimination, resulting in structural and, in some cases, functional changes in target proteins and are also linked to EV biogenesis. This study describes for the first time EVs isolated from cod mucosa. Mucosal EVs were characterised by electron microscopy, nanoparticle tracking analysis and EV-specific surface markers. Cod mucosal EVs were found to carry PAD, complement component C3 and C-reactive proteins. C3 was found to be deiminated in both whole mucus and mucosal EVs, with some differences, and further 6 deiminated immune and cytoskeletal proteins were identified in EVs by LC-MS/MS analysis. As mucosal surfaces of teleost fish reflect human mucosal surfaces, these findings may provide useful insights into roles of EVs in mucosal immunity throughout phylogeny

„Whose interest matter prevail?“: The lived experience of managers and specialists of the effect of published application lists on applicants in governmental hiring

Birting umsækjendalista í opinberum ráðningum er umræðuefni sem heitar umræður skapast oft um. Grein þessi byggist á niðurstöðum úr rannsókn þar sem skoðuð var reynsla og upplifun stjórnenda og sérfræðinga á áhrifum birtingar lista yfir umsækjendur í opinberum ráðningum. Samkvæmt niðurstöðum rannsóknarinnar er ákveðinn fælingarmáttur fólginn í birtingunni. Tekin voru viðtöl við stjórnendur og sérfræðinga sem hafa reynslu af ráðningum og þekkingu á áhrifum birtingar umsækjendalista á umsækjendur í opinberum ráðningum. Leitast var við að öðlast frekari skilning á ferli opinberra ráðninga og hvort þessir sérfræðingar teldu að birtingin hefði fælingarmátt. Rannsóknargögnin voru túlkuð og greind samkvæmt fyrirbærafræðilegri aðferðafræði. Niðurstöður sýna fram á að þeir stjórnendur og sérfræðingar sem leitað var til í þessari rannsókn telja að fælingarmáttur í birtingu á umsækjendalistum í opinberum ráðningum sé afar mikill. Talið er að um 10-35% umsækjenda dragi umsókn sína til baka. Þetta getur haft mjög neikvæð áhrif á ráðningarferlið í heild. Nafnbirting getur því leitt til þess að hæfasti umsækjandinn sækir ekki um starfið. Í lokin gefa niðurstöður rannsóknarinnar einnig til kynna að kerfisbundin birting á listum yfir umsækjendur þarfnist endurskoðunar. Þannig má auka líkur á því að sá hæfasti verði ráðinn og að fagmennska ráði för í umsóknar- og ráðningarferli í opinberum ráðningum.In this study the researchers set out to gain insight into the experience and attitude of managers and specialists concerning display of applicant lists in governmental hiring. The study focused on whether publication of application lists would have repellent effect on applicants and consequently if public employees had the appropriate qualifications. Information was gathered with semi-structured interviews with managers in organizations, ministries, municipals and experts in recruitment and their experience on publication of applicant lists probed. The data were analyzed and interpreted according to phenomenological methodology. Highlights of the study are that publication of applicants have repellent effects and it is estimated that about 10-35% of applicants withdraw their application when it is clear that a disclosure will occur. The results indicate that the managers and specialists in this study believe that published application list in governmental hiring is very repellent for prospective applicants and that the publications cause them to withdraw their application. As the names of the applicants will be published, the applicants withdraw and as a result of that, the most qualified candidate for the job will not be hired. Therefore the employer will not get the most qualified applicant for the job. Finally, the results of this study indicate that systematic publication of the application lists need to be re-examined in order to increase the possibility that the best and most qualified candidate will be hired and professionalism will prevail in the application and hiring process in governmental hiring.Peer Reviewe

Pentraxins CRP-I and CRP-II are post-translationally deiminated and differ in tissue specificity in cod (Gadus morhua L.) ontogeny

Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin. This indicates differing roles for the two pentraxin types in immune responses and tissue remodelling, also elucidating novel roles for CRP-I in the nervous system. The presence of deimination positive bands for cod CRPs varied somewhat between mucus and serum, possibly facilitating CRP protein moonlighting, allowing the same protein to exhibit a range of biological functions and thus meeting different functional requirements in different tissues. The presented findings may further current understanding of the diverse roles of pentraxins in teleost immune defences and tissue remodelling, as well as in various human pathologies, including autoimmune diseases, amyloidosis and cancer

Post-translational Protein Deimination in Cod (Gadus morhua L.) Ontogeny: Novel Roles in Tissue Remodelling and Mucosal Immune Defences?

Peptidylarginine deiminases (PADs) are calcium dependent enzymes with physiological and pathophysiological roles conserved throughout phylogeny. PADs promote post-translational deimination of protein arginine to citrulline, altering the structure and function of target proteins. Deiminated proteins were detected in the early developmental stages of cod from 11 days post fertilisation to 70 days post hatching. Deiminated proteins were present in mucosal surfaces and in liver, pancreas, spleen, gut, muscle, brain and eye during early cod larval development. Deiminated protein targets identified in skin mucosa included nuclear histones; cytoskeletal proteins such as tubulin and beta-actin; metabolic and immune related proteins such as galectin, mannan-binding lectin, toll-like receptor, kininogen, Beta2-microglobulin, aldehyde dehydrogenase, bloodthirsty and preproapolipoprotein A-I. Deiminated histone H3, a marker for anti-pathogenic neutrophil extracellular traps, was particularly elevated in mucosal tissues in immunostimulated cod larvae. PAD-mediated protein deimination may facilitate protein moonlighting, allowing the same protein to exhibit a range of biological functions, in tissue remodelling and mucosal immune defences in teleost ontogeny

Neurocognitive enhancement or impairment? A systematic meta-analysis of prescription stimulant effects on processing speed, decision-making, planning, and cognitive perseveration

Increasing numbers of adults, particularly college students, are misusing prescription stimulants primarily for cognitive/academic enhancement, so it is critical to explore whether empirical findings support neurocognitive benefits of prescription stimulants. Previous meta-analytic studies have supported small benefits from prescription stimulants for the cognitive domains of inhibitory control and memory; however, no meta-analytic studies have examined the effects on processing speed or the potential impairment on other domains of cognition, including planning, decision-making, and cognitive perseveration. Therefore, the present study conducted a meta-analysis of the available literature examining the effects of prescription stimulants on specific measures of processing speed, planning, decision-making, and cognitive perseveration among healthy adult populations. The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI [0.077, 0.488]; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however, findings are limited by the small number of studies examining these outcomes. Findings support that prescription stimulant medication may indeed act as a neurocognitive enhancer for accuracy measures of processing speed without impeding other areas of cognition. Considering that adults are already engaging in illegal use of prescription stimulants for academic enhancement, as well as the potential for stimulant misuse to have serious side effects, the establishment of public policies informed by interdisciplinary research surrounding this issue, whether restrictive or liberal, is of critical importance

Peptidylarginine deiminase and deiminated proteins are detected throughout early halibut ontogeny - Complement components C3 and C4 are post-translationally deiminated in halibut (Hippoglossus hippoglossus L.)

Post-translational protein deimination is mediated by peptidylarginine deiminases (PADs), which are calcium dependent enzymes conserved throughout phylogeny with physiological and pathophysiological roles. Protein deimination occurs via the conversion of protein arginine into citrulline, leading to structural and functional changes in target proteins. In a continuous series of early halibut development from 37 to 1050° d, PAD, total deiminated proteins and deiminated histone H3 showed variation in temporal and spatial detection in various organs including yolksac, muscle, skin, liver, brain, eye, spinal cord, chondrocytes, heart, intestines, kidney and pancreas throughout early ontogeny. For the first time in any species, deimination of complement components C3 and C4 is shown in halibut serum, indicating a novel mechanism of complement regulation in immune responses and homeostasis. Proteomic analysis of deiminated target proteins in halibut serum further identified complement components C5, C7, C8 C9 and C1 inhibitor, as well as various other immunogenic, metabolic, cytoskeletal and nuclear proteins. Post-translational deimination may facilitate protein moonlighting, an evolutionary conserved phenomenon, allowing one polypeptide chain to carry out various functions to meet functional requirements for diverse roles in immune defences and tissue remodelling

Coherent electronic transport in a multimode quantum channel with Gaussian-type scatterers

Coherent electron transport through a quantum channel in the presence of a general extended scattering potential is investigated using a T-matrix Lippmann-Schwinger approach. The formalism is applied to a quantum wire with Gaussian type scattering potentials, which can be used to model a single impurity, a quantum dot or more complicated structures in the wire. The well known dips in the conductance in the presence of attractive impurities is reproduced. A resonant transmission peak in the conductance is seen as the energy of the incident electron coincides with an energy level in the quantum dot. The conductance through a quantum wire in the presence of an asymmetric potential are also shown. In the case of a narrow potential parallel to the wire we find that two dips appear in the same subband which we ascribe to two quasi bound states originating from the next evanescent mode.Comment: RevTeX with 14 postscript figures include

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world

CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldA T-C polymorphism in the promoter region of the CYP17 gene has been associated with male and female breast cancer risk as well as early-onset familial breast cancer. The potential role of this polymorphism was investigated in relation to breast cancer risk in Icelandic male and female carriers and noncarriers of a BRCA2 mutation. The study population consisted of 39 male and 523 female breast cancer cases and 309 male and 395 female controls. Of the cases, 15 males and 55 females carried a BRCA2 mutation. We did not find a significant association between male breast cancer risk and CYP17 genotypes. Among male breast cancer cases, the frequency of the CC genotype was higher among carriers of the 999del5 mutation (33.3%) than noncarriers (16.7%), although this difference also did not reach a statistical significance. No association was observed with breast cancer risk among females irrespective of menopausal status, stage of the disease or BRCA2 status. Our findings do not indicate a role for the CYP17 T-C polymorphism in female breast cancer, but a role in male carriers of a BRCA2 mutation could not be excluded because of the small sample size