Heteroagglutinins and their significance in baboon hepatic xenotransplantation

The role of preformed xenoreactive antibodies in xenograft recipients is unknown. Humans and baboons possess red cell agglutinating activity associated with isohemagglutinins and heteroagglutinins (HA). We examined the role of HA in two patients who received ABO-identical baboon livers. Human antibaboon HA were assessed by correlating serial titers with studies for rejection. Serial direct antiglobulin testing (DAT) was used to detect baboon antihuman HA, potentially produced by transplanted passenger lymphocytes. Patient 1 survived 70 days. The human antibaboon HA titers remained essentially unchanged from preoperative values. Although hyperacute rejection did not occur, and there was only mild cellular rejection, liver function was suboptimal. Postreperfusion immunoglobulin and complement deposition and histologic changes suggested complement-mediated injury. DAT testing was negative except for passively acquired anti-A from transfusion. At autopsy there was marked bile stasis, but no rejection. Patient 2 survived 26 days with essentially unchanged HA titers until preterminal. Although there was no hyperacute rejection and only mild humoral rejection (without cellular rejection), suboptimal liver function and bile stasis were again noted. Postreperfusion immunoglobulin and complement deposition again suggested com-plement-mediated injury. DAT testing was negative. At autopsy there was no rejection. Human antibaboon HA do not appear to be associated with hyperacute or cellular rejection, but their role in the complement-mediated injury, suspected in both cases, cannot be definitively excluded. Baboon antihuman HA were not detected in either patient. © 1995 by Williams and Wilkins

Rugby-specific small-sided games training is an effective alternative to stationary cycling at reducing clinical risk factors associated with the development of type 2 diabetes: A randomized, controlled trial

© 2015 Mendham 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. Introduction: The present study investigated whether rugby small-sided games (SSG) could be an effective alternative to continuous stationary cycling (CYC) training at reducing clinical risk factors associated with the development of type 2 diabetes mellitus (T2DM). Methods: Thirty-three middle-aged (48.6±6.6y), inactive men were randomized into a CYC (n=11), SSG (n=11), or control (CON, n=11) group. Participants trained 3d·wk-1 for 8 weeks, while control participants maintained normal activity and dietary patterns. Exercise duration was matched between groups, which involved CYC or SSG (four quarters, interspersed with 2- min passive recovery). Both training programs were designed to induce similar internal loads of maximal heart rate (∼80-85%HRmax) and rating of perceived exertion. Pre- and post-intervention testing included dual-energy x-ray absorptiometry scan, graded exercise test, fasting 2h oral glucose tolerance test and resting muscle biopsy. Western blotting was used to assess the content of skeletal muscle proteins associated with mitochondrial biogenesis and glucose regulation. Results: Both CYC and SSG increased VO2 at 80%HRmax, and reduced glycated haemoglobin, glucose area under the curve (AUC; SSG, -2.3±2.4; CYC -2.2±1.6 mmol·L1(120min)1; p1(120min)1; p0.05). There were no differences within or between conditions for protein content of peroxisome proliferator-activated receptor gamma coactivator-1α, sirtuin-1, p53, glucose transporter-4, protein kinase AKT/PKB, myocyte enhancer factor 2A, mitochondrial transcription factor, nuclear respiratory factor (NRF)-1, NRF-2 or mitochondrial complexes I-V (p>0.05). Conclusion: Rugby small-sided games is an effective alternative to continuous cycling for improving metabolic risk-factors associated with the prevention of T2DM. Despite such positive adaptations in clinical risk factors, there were no changes in the content of skeletal muscle proteins associated with glucose regulation and mitochondrial biogenesis. Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN1261300087471

An Empirical Planetesimal Belt Radius-Stellar Luminosity Relation

Resolved observations of millimetre-sized dust, tracing larger planetesimals, have pinpointed the location of 26 Edgeworth-Kuiper belt analogs. We report that a belt's distance $R$ to its host star correlates with the star's luminosity $L_{\star}$, following $R\propto L^{0.19}_{\star}$ with a low intrinsic scatter of $\sim$17%. Remarkably, our Edgeworth-Kuiper belt in the Solar System and the two CO snow lines imaged in protoplanetary disks lie close to this $R$-$L_{\star}$ relation, suggestive of an intrinsic relationship between protoplanetary disk structures and belt locations. To test the effect of bias on the relation, we use a Monte Carlo approach and simulate uncorrelated model populations of belts. We find that observational bias could produce the slope and intercept of the $R$-$L_{\star}$ relation, but is unable to reproduce its low scatter. We then repeat the simulation taking into account the collisional evolution of belts, following the steady state model that fits the belt population as observed through infrared excesses. This significantly improves the fit by lowering the scatter of the simulated $R$-$L_{\star}$ relation; however, this scatter remains only marginally consistent with the one observed. The inability of observational bias and collisional evolution alone to reproduce the tight relationship between belt radius and stellar luminosity could indicate that planetesimal belts form at preferential locations within protoplanetary disks. The similar trend for CO snow line locations would then indicate that the formation of planetesimals and/or planets in the outer regions of planetary systems is linked to the volatility of their building blocks, as postulated by planet formation models

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Serious games may improve understanding, involvement, engagement, reasoning and inquiry, and have been successfully used in schools. Recent studies show that serious games are sometimes misused, and not always easy to integrate in an instructional environment. It is often unclear how a game contributes to student learning, or how it should be used in a course. This paper proposes a method to support the analysis, design, development, and use of serious games in education. The method combines the widely used design model ADDIE with the instructional design method ‘10 steps to complex learning’. The method is applied in the development of the Moth game, which supports learning optics at the level of high school physics

Stakeholder discourse coalitions and polarisation in the hen harrier conservation debate in news media

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All the relevant data are available in the Nexis UK news online database.Conservation conflicts are complex and can be deep-rooted, with stakeholders holding entrenched policy positions. The actors involved producing verbal interconnected interactions that form policy debates. Thus, conservation debates can be viewed as network phenomena with stakeholders forming coalitions in support of, or opposition to, certain policies and practices. We used Discourse Network Analysis of print media to investigate the structure and dynamics of the stakeholder debate around the management of hen harriers Circus cyaneus, a bird of prey at the centre of a long-standing conservation conflict in the United Kingdom. We aimed to determine whether the structure of discourse coalitions changed among the diverse aspects of the debate and whether the polarisation of the debate has changed through time. Our search and selection criteria led to the analysis of 737 statements within 131 newspaper articles published from August 1993 to December 2019. We show that, while the discourse network of the overall debate is quite unstructured, actors formed divergent coalitions when defining the conservation problem and its solutions. In contrast, discourses converged around reactions with positive or negative emotions in relation to events and issues of hen harrier conservation. Polarisation among actors has increased over time and peaked in the second half of the 2010s, concurrent with the release of the species recovery plan. Our study highlights the value of analysing discourse networks in conservation policy debates. Discourse networks reveal which aspects of any conservation problem cause stakeholders to converge or diverge and can identify periods of intensified debate that, ultimately, contribute to informing conflict mitigation and resolution processes. Read the free Plain Language Summary for this article on the Journal blog.University of ExeterNatural Englan

Sample Preparation for N-Glycosylation Analysis of Therapeutic Monoclonal Antibodies by Electrophoresis

There are a considerable number of biopharmaceuticals that have been approved for clinical use in the past decade. Over half of these new generation drugs are glycoproteins, such as monoclonal antibodies or other recombinant glycoproteins, which are mostly produced in mammalian cell lines. The linked carbohydrate moieties affect not only their physicochemical properties and thermal stability but also crucial features like receptor-binding activity, circulating half-life, as well as immunogenicity. The structural diversity of these attached glycans can be manifested in altered monosaccharide composition and linkages/positions among the monosaccharide building blocks. In addition, as more and more biosimilar products hit the market, understanding the effects of their glycosylation modifi cation has become a recent target in effi cacy and safety issues. To ensure consistent quality of these products, glycosylation profi les have to be monitored and controlled in all steps of the manufacturing process, i.e., from clone selection to lot release. In this paper, we describe some of the recently introduced and commonly used sample preparation techniques for capillary electrophoresis (CE)-based profi ling and structural elucidation of N-glycans. The presented pro- tocols include protein A affi nity partitioning of monoclonal antibodies (mAbs), enzymatic release of the N-linked glycans, labeling of the liberated carbohydrates, reaction mixture purifi cation techniques to remove the excess labeling reagent, and high-resolution and rapid capillary electrophoresis-laser-induced fl uorescence (CE-LIF)-based profi ling of the labeled and purifi ed N-glycans

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al