The gift of life: an existential phenomenological exploration of receiving a lifesaving organ transplant and how this affects life subsequently

At present, there is little research conducted on organ transplantation from the perspective of the organ recipient. This study aimed to explore the experience of undergoing lifesaving organ transplantation and how this may affect life subsequently. For the purpose of this research, lifesaving transplants constituted as solid organ transplants, these being heart, lung, liver, and kidney. Six participants were interviewed using semi-structured interviews focusing on the experience of undergoing the transplantation procedure, and how this affected their life following this. The data in the form of the participants' accounts were analysed using Interpretative Phenomenological Analysis - IPA. Five superordinate themes were identified with 19 subordinate themes falling within these. The superordinate themes were; Embodied Experience which related to the participants’ physical world and their experiences of this, Life & Death relating to the participants’ experience of existence and mortality, Relationships relating to the participants’ actual or intended modes of relating to others in the world, Temporality relating to the participants’ experience of time, and The Psychological relating to the participants’ experiences of their inner world and the relationship they hold with themselves. Consideration and discussion of these themes were conducted, highlighting the implications these findings hold for the field of Counselling Psychology and Psychotherapy, with a nod to Existential literature and philosophy interwoven within this. The study concludes that organ recipients undergoing transplantation experience an array of bio-psycho-social-spiritual issues that professionals working with this population need to be aware of. It is argued that appropriate and sufficient evidence-based interventions should be developed and offered to all those undergoing the transplant treatment as standard in the provision of care provided to this population. Unfortunately, at present psychological support for organ recipients is only offered as and when a need ‘arises’

Evolutionary Computing for Operating Point Analysis of Nonlinear Circuits

The DC operating point of an electronic circuit is conventionally found using the Newton-Raphson method. This method is not globally convergent and can only find one solution of the circuit at a time. In this paper, evolutionary computing methods, including Genetic Algorithms, Evolutionary Programming, Evolutionary Strategies and Differential Evolution are explored as possible alternatives to Newton-Raphson. These techniques have been implemented in a trial simulator. Results are presented showing that Evolutionary Computing methods are globally convergent and can find multiple solutions to circuits. The CPU time for these new methods is poor compared with Newton-Raphson, but better implementations and the use of hybrid methods suggest that further work in this area would prove fruitful

Seminar Capital: An Exploration of the Enduring Social and Pedagogical Benefits of Seminar Engagement

This article presents findings from a small-scale qualitative case study exploring how engagement with seminars might prompt a sense of community amongst students. Further, it considered if such engagement might afford students ‘seminar capital’, a form of academic social capital (Bourdieu 1977 in Preece 2010). The study also aimed to uncover how seminar pedagogy can support students to develop their academic voice and connect with others in learning communities. Reflecting on emergent learning (Bourner 2003) supports students to move between a range of language codes (Preece 2010). Students in the study reported that seminar discussions supported their conceptual understanding, consolidated their academic language skills and offered opportunities to apply their knowledge to their assessments. This took place within an emerging positioning of relationships between peers and lecturers

A 3‐D Model of Gas Generation, Migration, and Gas Hydrate Formation at a Young Convergent Margin (Hikurangi Margin, New Zealand)

We present a three-dimensional gas hydrate systems model of the southern Hikurangi subduction margin in eastern New Zealand. The model integrates thermal and microbial gas generation, migration, and hydrate formation. Modeling these processes has improved the understanding of factors controlling hydrate distribution. Three spatial trends of concentrated hydrate occurrence are predicted. The first trend (I) is aligned with the principal deformation front in the overriding Australian plate. Concentrated hydrate deposits are predicted at or near the apexes of anticlines and to be mainly sourced from focused migration and recycling of microbial gas generated beneath the hydrate stability zone. A second predicted trend (II) is related to deformation in the subducting Pacific plate associated with former Mesozoic subduction beneath Gondwana and the modern Pacific-Australian plate boundary. This trend is enhanced by increased advection of thermogenic gas through permeable layers in the subducting plate and focused migration into the Neogene basin fill above Cretaceous-Paleogene structures. The third trend (III) follows the northern margin of the Hikurangi Channel and is related to the presence of buried strata of the Hikurangi Channel system. The predicted trends are consistent with pronounced seismic reflection anomalies related to free gas in the pore space and strength of the bottom-simulating reflection. However, only trend I is also associated with clear and widespread seismic indications of concentrated gas hydrate. Total predicted hydrate masses at the southern Hikurangi Margin are between 52,800 and 69,800 Mt. This equates to 3.4–4.5 Mt hydrate/km2, containing 6.33 × 108–8.38 × 108 m3/km2 of methane

An amphipathic helix enables septins to sense micrometer-scale membrane curvature

© The Authors, 2019. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 4.0 International License. The definitive version was published in Journal of Cell Biology (2019), doi:10.1083/jcb.201807211.Cell shape is well described by membrane curvature. Septins are filament-forming, GTP-binding proteins that assemble on positive, micrometer-scale curvatures. Here, we examine the molecular basis of curvature sensing by septins. We show that differences in affinity and the number of binding sites drive curvature-specific adsorption of septins. Moreover, we find septin assembly onto curved membranes is cooperative and show that geometry influences higher-order arrangement of septin filaments. Although septins must form polymers to stay associated with membranes, septin filaments do not have to span micrometers in length to sense curvature, as we find that single-septin complexes have curvature-dependent association rates. We trace this ability to an amphipathic helix (AH) located on the C-terminus of Cdc12. The AH domain is necessary and sufficient for curvature sensing both in vitro and in vivo. These data show that curvature sensing by septins operates at much smaller length scales than the micrometer curvatures being detected.We thank the Gladfelter laboratory and Danny Lew for useful discussions, Matthias Garten for ideas in setting up the rod assay, and the University of North Carolina EM facility (Victoria Madden and Kristen White) for support with scanning electron microscope. This work was supported by a Howard Hughes Medical Institute Faculty Scholars award to A.S. Gladfelter, and K.S. Cannon was supported in part by a grant from the National Institute of General Medical Sciences under award T32 GM119999.2019-07-0

Recent advances in cyanamide chemistry: synthesis and applications

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry

Spatial heterogeneity of the cytosol revealed by machine learning-based 3D particle tracking

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in McLaughlin, G. A., Langdon, E. M., Crutchley, J. M., Holt, L. J., Forest, M. G., Newby, J. M., & Gladfelter, A. S. (2020). Spatial heterogeneity of the cytosol revealed by machine learning-based 3D particle tracking. Molecular Biology of the Cell, 31(14), 1498-1511, doi:10.1091/mbc.E20-03-0210.The spatial structure and physical properties of the cytosol are not well understood. Measurements of the material state of the cytosol are challenging due to its spatial and temporal heterogeneity. Recent development of genetically encoded multimeric nanoparticles (GEMs) has opened up study of the cytosol at the length scales of multiprotein complexes (20-60 nm). We developed an image analysis pipeline for 3D imaging of GEMs in the context of large, multinucleate fungi where there is evidence of functional compartmentalization of the cytosol for both the nuclear division cycle and branching. We applied a neural network to track particles in 3D and then created quantitative visualizations of spatially varying diffusivity. Using this pipeline to analyze spatial diffusivity patterns, we found that there is substantial variability in the properties of the cytosol. We detected zones where GEMs display especially low diffusivity at hyphal tips and near some nuclei, showing that the physical state of the cytosol varies spatially within a single cell. Additionally, we observed significant cell-to-cell variability in the average diffusivity of GEMs. Thus, the physical properties of the cytosol vary substantially in time and space and can be a source of heterogeneity within individual cells and across populations.We would like to thank the 2016 Physiology course and Christina Termini at the Marine Biological Laboratory in Woods Hole, MA, Gregory Brittingham, and Marcus Roper for initial experiments and perspectives on pipeline. We thank David Adalsteinsson for help with DataTank software and many conversations about image analysis on large datasets. We thank Emmanual Levy (Weizmann Institute) for providing plasmids encoding synthetic phase separating peptides. This work was supported by Google Cloud, the National Science Foundation (NSF), the National Institutes of Health (NIH), and the Natural Sciences and Engineering Research Council of Canada (NSERC). ASG, EML, and GAM were supported by the NSF (RoLs: 1840273), HHMI faculty scholar award and the NIH (R01GM081506). JMN was supported by the NSERC (RGPIN-2019-06435, RGPAS-2019-00014, DGECR-2019-00321) and the NSF (DMS-171474). MGF was supported by the NSF (DMS-1816630, DMS-1664645). LJH was supported by the NIH (R01GM132447)

Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Woods, B. L., Cannon, K. S., Vogt, E. J. D., Crutchley, J. M., & Gladfelter, A. S. Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling. Molecular Biology of the Cell, 32(20), (2021): mbcE20050303, https://doi.org/10.1091/mbc.E20-05-0303.The curvature of the membrane defines cell shape. Septins are GTP-binding proteins that assemble into heteromeric complexes and polymerize into filaments at areas of micron-scale membrane curvature. An amphipathic helix (AH) domain within the septin complex is necessary and sufficient for septins to preferentially assemble onto micron-scale curvature. Here we report that the nonessential fungal septin, Shs1, also has an AH domain capable of recognizing membrane curvature. In a septin mutant strain lacking a fully functional Cdc12 AH domain (cdc12-6), the C-terminal extension of Shs1, containing an AH domain, becomes essential. Additionally, we find that the Cdc12 AH domain is important for regulating septin filament bundling, suggesting septin AH domains have multiple, distinct functions and that bundling and membrane binding may be coordinately controlled.This work was supported by National Institutes of Health (NIH) Grant no. R01GM-130934 to A.S.G. B.L.W. was supported by the NIH Training Grant no. 2T32AI052080-16. K.S.C. and E.J.D.V. were supported in part by a grant from the National Institute of General Medical Sciences under award T32 GM119999

mRNA structure determines specificity of a polyQ-driven phase separation

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of American Association for the Advancement of Science for personal use, not for redistribution. The definitive version was published in American Association for the Advancement of Science 360 (2018): 922-927, doi:10.1126/science.aar7432.RNA promotes liquid-liquid phase separation (LLPS) to build membrane-less compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here we report that secondary structure allows mRNAs to self-associate and determines if an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.This work was supported by NIH GM R01- GM081506, the HHMI Faculty Scholars program, R35 GM122532, ACS 130845-RSG-17-114- 01-RMC, NIH 1DP2 GM105453, and NIH R01 GM115631