Megalin in normal tissues and carcinoma cells carries oligo/poly α2,8 deaminoneuraminic acid as a unique posttranslational modification

In rat kidney, megalin, a member of the low density lipoprotein receptor gene family, is the sole glycoprotein which carries oligo/poly α2,8 deaminoneuraminic acid (KDN) as a posttranslational modification. We have investigated immunoprecipitated megalin from rat brain, lung and placenta, mouse yolk sac carcinoma and megalin synthesizing carcinoma cell lines, for presence of this unique glycan structure. Our immunoblot analysis revealed the presence of oligo/poly α2,8 KDN on megalin in all the studied normal tissues and carcinoma cells. Furthermore, it is demonstrated that to be part of oligosaccharides O-glycosidically linked to megali

Two Forms of Activation-Induced Cytidine Deaminase Differing in Their Ability to Bind Agarose

Background: Activation-induced cytidine deaminase (AID) is a B-cell-specific DNA mutator that plays a key role in the formation of the secondary antibody repertoire in germinal center B cells. In the search for binding partners, protein coimmunoprecipitation assays are often performed, generally with agarose beads. Methodology/Principal Findings: We found that, regardless of whether cell lysates containing exogenous or endogenous AID were examined, one of two mouse AID forms bound to agarose alone. Conclusions/Significance: These binding characteristics may be due to the known post-translational modifications of AID; they may also need to be considered in coimmunoprecipitation experiments to avoid false-positive results

Survey among FELASA members about rehoming of animals used for scientific and educational purposes

Rehoming is an important fate, which should be considered for animals used for scientific and educational purposes, and which is highlighted in the European Directive 2010/63 EU. In 2018, the Federation of European Laboratory Animal Science Associations (FELASA) convened a working group to review current literature and identify existing practices with the aim of issuing general recommendations on the rehoming of research animals. In order to understand the number and species of animals being rehomed and which species and information to include in the recommendations, the working group launched a survey that was distributed among FELASA members, yielding 97 valid records for analysis. Most respondents of the survey considered the rehoming of cats, dogs, mice, rats, rabbits, pigs and minipigs. The most important issues reported by the respondents were related to availability/suitability of animals, availability of adopters and legal issues. Based on the data and information collected in this survey, the working group decided on the format and content of the future recommendations: a first section containing a general protocol for rehoming, addressing the issues raised by the respondents, and a second section containing species-specific information and advice about cats, dogs, small prey mammals, equines, primates, camelids and minipigs

FELASA recommendations for the rehoming of animals used for scientific and educational purposes

Directive 2010/63/EU of the European Parliament and the Council of 22 September 2010 states that at the end of a procedure, the most appropriate decision on the future of an animal previously used or intended for use in scientific procedures should be taken on the basis of animal welfare and potential risks to the environment. Member States may allow animals to be rehomed provided the health of the animal allows it, there is no danger to public health, animal health or the environment and if appropriate measures have been taken to safeguard the wellbeing of the animal. In countries where rehoming is permitted, it is the responsibility of the Animal Welfare Body to advise on a rehoming scheme which must include appropriate socialization in order to help facilitate successful rehoming, avoid unnecessary distress to the animals and guarantee public safety. This paper reviews the EU legislation, existing guidance, current literature and best practice to define rehoming, sets out general considerations for rehoming laboratory animals including socialization and provides practical advice on the steps required in a rehoming scheme. For those species most frequently rehomed, more detailed species-specific sections are included

Forging connections, pursuing social justice: a tribute to Maarten Bavinck’s conceptual and institution-building contributions to maritime studies

This paper is written in recognition of the contributions that Maarten Bavinck has made to the field of maritime studies and for the inspiration that he has been for many. It is hard to separate Maarten’s academic and institution-building contributions from his personal qualities, particularly his interest in human relationships. Maarten’s aptitude for building bridges between people, ideas, and institutions has allowed him to connect people in larger knowledge generation and action projects and forge new conceptual bridges. In addition to reflecting shortly on Maarten's key role in establishing the Centre for Maritime Research (MARE) as a institutional anchor in maritime studies, this paper reviews on some of his important and original contributions to four academic domains: legal pluralism, interactive governance, the study of fisheries conflicts, and the environment-development interface. Common threads across these domains include his long-term commitment to meticulous fieldwork in South Asia that grounds his work so firmly, his focus on achieving a more socially just use of marine and coastal resources, and his pragmatic approach that has led to original connections across distinct conceptual and institutional fields

The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

Background A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done. Methods In this systematic review and meta-analysis, we searched five electronic databases for cross-sectional, case-control, or cohort studies published up to May 6, 2016, reporting risks of health outcomes, consisting of substance use, sexual health, mental health, weight and physical exercise, violence, and physical health status and conditions, associated with multiple ACEs. We selected articles that presented risk estimates for individuals with at least four ACEs compared with those with none for outcomes with sufficient data for meta-analysis (at least four populations). Included studies also focused on adults aged at least 18 years with a sample size of at least 100. We excluded studies based on high-risk or clinical populations. We extracted data from published reports. We calculated pooled odds ratios (ORs) using a random-effects model. Findings Of 11 621 references identified by the search, 37 included studies provided risk estimates for 23 outcomes, with a total of 253 719 participants. Individuals with at least four ACEs were at increased risk of all health outcomes compared with individuals with no ACEs. Associations were weak or modest for physical inactivity, overweight or obesity, and diabetes (ORs of less than two); moderate for smoking, heavy alcohol use, poor self-rated health, cancer, heart disease, and respiratory disease (ORs of two to three), strong for sexual risk taking, mental ill health, and problematic alcohol use (ORs of more than three to six), and strongest for problematic drug use and interpersonal and self-directed violence (ORs of more than seven). We identified considerable heterogeneity (I 2 of > 75%) between estimates for almost half of the outcomes. Interpretation To have multiple ACEs is a major risk factor for many health conditions. The outcomes most strongly associated with multiple ACEs represent ACE risks for the next generation (eg, violence, mental illness, and substance use). To sustain improvements in public health requires a shift in focus to include prevention of ACEs, resilience building, and ACE-informed service provision. The Sustainable Development Goals provide a global platform to reduce ACEs and their life-course effect on health. Funding Public Health Wales. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licens

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Exploring narrative novelties in VR.

Initial expectations about the interactive affordances of VR were often inspired by science fiction and technological fantasies rather than based on actual technical possibilities. In these futuristic accounts of VR, interactors would have the opportunity to fully engage with the characters that inhabit the story world, in ways that would feel so natural that it would be indistinguishable from reality. In ‘real’ reality however, the actual production of VR has turned out to be considerably more complicated. To provide a realistic impression of the actual possibilities of VR, this study presents four widely acclaimed contemporary VR experiences (Wolves in the Walls, The Line, Down the Rabbit Hole and A Fisherman’s Tale) and reviews them from a media theory and communication science perspective. We discuss whether and how the concepts identification, parasocial interaction, ‘breaking the fourth wall’ and spatial and narrative presence can still be applied to these VR case studies, eventually aiming to contribute some rudimentary insights into the range of possible media conventions that narrative VR may contain

Megalin in normal tissues and carcinoma cells carries oligo/poly α2,8 deaminoneuraminic acid as a unique posttranslational modification

In rat kidney, megalin, a member of the low density lipoprotein receptor gene family, is the sole glycoprotein which carries oligo/poly α2,8 deaminoneuraminic acid (KDN) as a posttranslational modification. We have investigated immunoprecipitated megalin from rat brain, lung and placenta, mouse yolk sac carcinoma and megalin synthesizing carcinoma cell lines, for presence of this unique glycan structure. Our immunoblot analysis revealed the presence of oligo/poly α2,8 KDN on megalin in all the studied normal tissues and carcinoma cells. Furthermore, it is demonstrated that to be part of oligosaccharides O-glycosidically linked to megali