Weak carbohydrate-carbohydrate interactions in membrane adhesion are fuzzy and generic

Carbohydrates such as the trisaccharide motif LeX are key constituents of cell surfaces. Despite intense research, the interactions between carbohydrates of apposing cells or membranes are not well understood. In this article, we investigate carbohydrate-carbohydrate interactions in membrane adhesion as well as in solution with extensive atomistic molecular dynamics simulations that exceed the simulation times of previous studies by orders of magnitude. For LeX, we obtain association constants of soluble carbohydrates, adhesion energies of lipid-anchored carbohydrates, and maximally sustained forces of carbohydrate complexes in membrane adhesion that are in good agreement with experimental results in the literature. Our simulations thus appear to provide a realistic, detailed picture of LeX-LeX interactions in solution and during membrane adhesion. In this picture, the LeX-LeX interactions are fuzzy, i.e. LeX pairs interact in a large variety of short-lived, bound conformations. For the synthetic tetrasaccharide Lac 2, which is composed of two lactose units, we observe similarly fuzzy interactions and obtain association constants of both soluble and lipid-anchored variants that are comparable to the corresponding association constants of LeX. The fuzzy, weak carbohydrate-carbohydrate interactions quantified in our simulations thus appear to be a generic feature of small, neutral carbohydrates such as LeX and Lac 2.Comment: 12 pages, 9 figure

Emerging Era of Biomolecular Membrane Simulations: Automated Physically-Justified Force Field Development and Quality-Evaluated Databanks

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Transcriptional profiling of pea ABR17 mediated changes in gene expression in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Pathogenesis-related proteins belonging to group 10 (PR10) are elevated in response to biotic and abiotic stresses in plants. Previously, we have shown a drastic salinity-induced increase in the levels of ABR17, a member of the PR10 family, in pea. Furthermore, we have also demonstrated that the constitutive expression of pea <it>ABR17 </it>cDNA in <it>Arabidopsis thaliana </it>and <it>Brassica napus </it>enhances their germination and early seedling growth under stress. Although it has been reported that several members of the PR10 family including ABR17 possess RNase activity, the exact mechanism by which the aforementioned characteristics are conferred by ABR17 is unknown at this time. We hypothesized that a study of differences in transcriptome between wild type (WT) and <it>ABR17 </it>transgenic <it>A. thaliana </it>may shed light on this process.</p> <p>Results</p> <p>The molecular changes brought about by the expression of pea <it>ABR17 </it>cDNA in <it>A. thaliana </it>in the presence or absence of salt stress were investigated using microarrays consisting of 70-mer oligonucleotide probes representing 23,686 <it>Arabidopsis </it>genes. Statistical analysis identified number of genes which were over represented among up- or down-regulated transcripts in the transgenic line. Our results highlight the important roles of many abscisic acid (ABA) and cytokinin (CK) responsive genes in <it>ABR17 </it>transgenic lines. Although the transcriptional changes followed a general salt response theme in both WT and transgenic seedlings under salt stress, many genes exhibited differential expression patterns when the transgenic and WT lines were compared. These genes include plant defensins, heat shock proteins, other defense related genes, and several transcriptional factors. Our microarray results for selected genes were validated using quantitative real-time PCR.</p> <p>Conclusion</p> <p>Transcriptional analysis in <it>ABR17 </it>transgenic <it>Arabidopsis </it>plants, both under normal and saline conditions, revealed significant changes in abundance of transcripts for many stress responsive genes, as well as those related to plant growth and development. Our results also suggest that <it>ABR17 </it>may mediate stress tolerance through the modulation of many ABA- and CK-responsive genes and may further our understanding of the role of ABR17 in mediating plant stress responses.</p

The impact of supportive nursing care on the needs of men with prostate cancer: a study across seven European countries

Background: prostate cancer is for many men a chronic disease with a long life expectancy after treatment. The impact of prostate cancer therapy on men has been well defined, however, explanation of the consequences of cancer treatment has not been modelled against the wider variables of long-term health-care provision. The aim of this study was to explore the parameters of unmet supportive care needs in men with prostate cancer in relation to the experience of nursing care. Methods: a survey was conducted among a volunteer sample of 1001 men with prostate cancer living in seven European countries. Results: at the time of the survey, 81% of the men had some unmet supportive care needs including psychological, sexual and health system and information needs. Logistic regression indicated that lack of post-treatment nursing care significantly predicted unmet need. Critically, men's contact with nurses and/or receipt of advice and support from nurses, for several different aspects of nursing care significantly had an impact on men's outcomes. Conclusion: Unmet need is related not only to disease and treatment factors but is also associated with the supportive care men received. Imperative to improving men's treatment outcomes is to also consider the access to nursing and the components of supportive care provided, especially after therapy

Exploring the activities and outcomes of digital teaching and learning of practical skills in higher education for the social and health care professions: a scoping review

Higher education for health care professionals faces numerous challenges. It is important to develop and apply methods supporting education, especially the practical skills. This scoping review aimed to explore the activities and learning outcomes of digital technology in practical skills teaching and learning in higher education for the social and health professions. Scoping review recommendations and the PRISMA-ScR checklist were applied. Randomized controlled trials published between 2016 and 2021 involving students in higher education who were taking courses in the social sciences and health care and reported interventions with digital technology activities and practices in practical teaching and learning were included. The CINAHL Plus, PubMed, Scopus, ERIC, and Sociological Abstracts/Social Services Abstracts databases were searched. Teaching methods were blended, e-learning or other online-based, and digital simulation-based activities. Teaching and learning environments, methods, resources, and activity characteristics varied, making a summary difficult. Interventions were developed in a face-to-face format prior to digitalization. The outcomes were measured at the knowledge level, not at the performance level. One-third of the studies showed a significant improvement in practical skills in the intervention group in comparison to the control conditions. The use of digital technology in the learning and teaching process have potential to develop of students' skills, knowledge, motivation, and attitudes. The pedagogy of technology use is decisive. The development of new digital methods for teaching and learning practical skills requires the engagement of students and teachers, in addition the researchers.publishersversionPeer reviewe

Interplay of Trans- and Cis-Interactions of Glycolipids in Membrane Adhesion

Glycolipids mediate stable membrane adhesion of potential biological relevance. In this article, we investigate the trans- and cis-interactions of glycolipids in molecular dynamics simulations and relate these interactions to the glycolipid-induced average separations of membranes obtained from neutron scattering experiments. We find that the cis-interactions between glycolipids in the same membrane leaflet tend to strengthen the trans-interactions between glycolipids in apposing leaflets. The trans-interactions of the glycolipids in our simulations require local membrane separations that are significantly smaller than the average membrane separations in the neutron scattering experiments, which indicates an important role of membrane shape fluctuations in glycolipid trans-binding. Simulations at the experimentally measured average membrane separations provide a molecular picture of the interplay between glycolipid attraction and steric repulsion of the fluctuating membranes probed in the experiments

Infection of the brown alga Ectocarpus siliculosus by the oomycete Eurychasma dicksonii induces oxidative stress and halogen metabolism

Acknowledgments We would like to thank the Aberdeen Proteome Facility, especially Phil Cash, David Stead and Evelyn Argo for assistance with 2D electrophoresis and mass spectrometry. M.S. gratefully acknowledges a Marie Curie PhD fellowship from the European Commission (ECOSUMMER, MEST-CT-2005-20501), a joint FEMS/ESCMID Research Fellowship and the Genomia Fund. C.M.M.G. is supported by a Marie Curie postdoctoral fellowship (MEIF-CT-2006-022837), a Marie Curie Re-Integration Grant (PERG03-GA-2008-230865) and a New Investigator grant from the UK Natural Environment Research Council (NERC, grant NE/J00460X/1). F.C.K. would like to thank NERC for funding (grants NE/D521522/1, NE/F012705/1 and Oceans 2025 / WP 4.5). L.J.G.-B., C.M.M.G., F.C.K. and P.W. would like to acknowledge funding from NERC for a Strategic Ocean Funding Initiative award (NE/F012578/1). Funding from the MASTS pooling initiative (Marine Alliance for Science and Technology for Scotland, funded by the Scottish Funding Council and contributing institutions; grant reference HR09011) and from the TOTAL Foundation (Paris) to F.C.K. is gratefully acknowledged. Finally, we would like to thank the two anonymous referees for constructive suggestions to improve our manuscript.Peer reviewedPublisher PD

Headgroup Structure and Cation Binding in Phosphatidylserine Lipid Bilayers

Phosphatidylserine (PS) is a negatively charged lipid type commonly found in eukaryotic membranes, where it interacts with proteins via nonspecific electrostatic interactions as well as via specific binding. Moreover, in the presence of calcium ions, PS lipids can induce membrane fusion and phase separation. Molecular details of these phenomena remain poorly understood, partly because accurate models to interpret the experimental data have not been available. Here we gather a set of previously published experimental NMR data of C-H bond order parameter magnitudes, vertical bar S-CH vertical bar, for pure PS and mixed PS:PC (phosphatidylcholine) lipid bilayers and augment this data set by measuring the signs of S-CH in the PS headgroup using S-DROSS solid-state NMR spectroscopy. The augmented data set is then used to assess the accuracy of the PS headgroup structures in, and the cation binding to, PS-containing membranes in the most commonly used classical molecular dynamics (MD) force fields including CHARMM36, Lipidl7, MacRog, Slipids, GROMOS-CKP, Berger, and variants. We show large discrepancies between different force fields and that none of them reproduces the NMR data within experimental accuracy. However, the best MD models can detect the most essential differences between PC and PS headgroup structures. The cation binding affinity is not captured correctly by any of the PS force fields-an observation that is in line with our previous results for PC lipids. Moreover, the simulated response of the PS headgroup to bound ions can differ from experiments even qualitatively. The collected experimental data set and simulation results will pave the way for development of lipid force fields that correctly describe the biologically relevant negatively charged membranes and their interactions with ions. This work is part of the NMRlipids open collaboration project (nmrlipids.blogspot.fi).Peer reviewe