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1دورية أكاديمية
المؤلفون: Patrick Reith, Svenja Braam, Niek Welkenhuysen, Sarah Lecinski, Jack Shepherd, Chris MacDonald, Mark C. Leake, Stefan Hohmann, Sviatlana Shashkova, Marija Cvijovic
المصدر: Microorganisms, Vol 10, Iss 3, p 590 (2022)
مصطلحات موضوعية: lithium, osmotic stress, macromolecular crowding, protein aggregation, long-term survival, yeast, Biology (General), QH301-705.5
الوصف: Lithium salts are used in the treatment of mood disorders, cancer, and Alzheimer’s disease. It has been shown to prolong life span in several phyla; however, not yet in budding yeast. In our study, we investigate the influence of lithium on yeast cells’ viability by characterizing protein aggregate formation, cell volume, and molecular crowding in the context of stress adaptation. While our data suggest a concentration-dependent growth inhibition caused by LiCl, we show an extended long-term survival rate as an effect of lithium addition upon glucose deprivation. We show that caloric restriction mitigates the negative impact of LiCl on cellular survival. Therefore, we suggest that lithium could affect glucose metabolism upon caloric restriction, which could explain the extended long-term survival observed in our study. We find furthermore that lithium chloride did not affect an immediate salt-induced Hsp104-dependent aggregate formation but cellular adaptation to H2O2 and acute glucose starvation. We presume that different salt types and concentrations interfere with effective Hsp104 recruitment or its ATP-dependent disaggregase activity as a response to salt stress. This work provides novel details of Li+ effect on live eukaryotic cells which may also be applicable in further research on the treatment of cancer, Alzheimer’s, or other age-related diseases in humans.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Konstantina Amoiradaki, Kate R. Bunting, Katherine M. Paine, Josephine E. Ayre, Karen Hogg, Kamilla M. E. Laidlaw, Chris MacDonald
المصدر: International Journal of Molecular Sciences, Vol 22, Iss 22, p 12477 (2021)
مصطلحات موضوعية: endocytosis, membrane trafficking, surface membrane proteins, histone deacetylase, transcription, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Intracellular trafficking pathways control residency and bioactivity of integral membrane proteins at the cell surface. Upon internalisation, surface cargo proteins can be delivered back to the plasma membrane via endosomal recycling pathways. Recycling is thought to be controlled at the metabolic and transcriptional level, but such mechanisms are not fully understood. In yeast, recycling of surface proteins can be triggered by cargo deubiquitination and a series of molecular factors have been implicated in this trafficking. In this study, we follow up on the observation that many subunits of the Rpd3 lysine deacetylase complex are required for recycling. We validate ten Rpd3-complex subunits in recycling using two distinct assays and developed tools to quantify both. Fluorescently labelled Rpd3 localises to the nucleus and complements recycling defects, which we hypothesised were mediated by modulated expression of Rpd3 target gene(s). Bioinformatics implicated 32 candidates that function downstream of Rpd3, which were over-expressed and assessed for capacity to suppress recycling defects of rpd3∆ cells. This effort yielded three hits: Sit4, Dit1 and Ldb7, which were validated with a lipid dye recycling assay. Additionally, the essential phosphatidylinositol-4-kinase Pik1 was shown to have a role in recycling. We propose recycling is governed by Rpd3 at the transcriptional level via multiple downstream target genes.
وصف الملف: electronic resource
العلاقة: https://www.mdpi.com/1422-0067/22/22/12477Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test
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3دورية أكاديمية
المؤلفون: Pat Hoddinott, Alex Pollock, Alicia O'Cathain, Isabel Boyer, Jane Taylor, Chris MacDonald, Sandy Oliver, Jenny L. Donovan
المصدر: F1000Research, Vol 7 (2018)
الوصف: International government guidance recommends patient and public involvement (PPI) to improve the relevance and quality of research. PPI is defined as research being carried out ‘with’ or ‘by’ patients and members of the public rather than ‘to’, ‘about’ or ‘for’ them (http://www.invo.org.ukTest/). Patient involvement is different from collecting data from patients as participants. Ethical considerations also differ. PPI is about patients actively contributing through discussion to decisions about research design, acceptability, relevance, conduct and governance from study conception to dissemination. Occasionally patients lead or do research. The research methods of PPI range from informal discussions to partnership research approaches such as action research, co-production and co-learning. This article discusses how researchers can involve patients when they are applying for research funding and considers some opportunities and pitfalls. It reviews research funder requirements, draws on the literature and our collective experiences as clinicians, patients, academics and members of UK funding panels.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Peng Xu, Hannah M Hankins, Chris MacDonald, Samuel J Erlinger, Meredith N Frazier, Nicholas S Diab, Robert C Piper, Lauren P Jackson, Jason A MacGurn, Todd R Graham
المصدر: eLife, Vol 6 (2017)
مصطلحات موضوعية: membrane trafficking, COPI, ubiquitin, SNARE, recycling, Medicine, Science, Biology (General), QH301-705.5
الوصف: The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β'-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β'-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway.
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Hari B Kamadurai, Yu Qiu, Alan Deng, Joseph S Harrison, Chris MacDonald, Marcelo Actis, Patrick Rodrigues, Darcie J Miller, Judith Souphron, Steven M Lewis, Igor Kurinov, Naoaki Fujii, Michal Hammel, Robert Piper, Brian Kuhlman, Brenda A Schulman
المصدر: eLife, Vol 2 (2013)
مصطلحات موضوعية: ubiquitin, HECT, E3 ligase, E2 conjugating enzyme, NEDD4, Rsp5, Medicine, Science, Biology (General), QH301-705.5
الوصف: Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3∼ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3∼ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation.
وصف الملف: electronic resource
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7كتاب
المؤلفون: Chris MacDonald, Alexei Marcoux
مصطلحات موضوعية: Business policy, Economics, business and management curriculum, pedagogy and didactics, business ethics, business, Encyclopaedia
الوصف: The authors’ aim in writing The Concise Encyclopedia of Business Ethics (CEBE) was to provide readers with a useful, concise overview of key issues in business ethics. Our aim is not to be exhaustive, but to provide key definitions, main areas of controversy, and pointers for further reading. It is hoped that it will provide a useful reference guide for students, as well as a starting point for scholars in adjacent fields. Our commitment to sticking to what we consider to be essential topics inevitably means that some readers will find that we have left out what they take to be important topics. For the most part, we stand by our editorial choices. However, as a digital document, it is possible that the CEBE will change and grow slightly over the coming years. Readers are free to provide feedback and suggestions by emailing the authors jointly at editors@bejr.org
العلاقة: https://figshare.com/articles/book/The_Concise_Encyclopedia_of_Business_Ethics/24147888Test
الإتاحة: https://doi.org/10.32920/24147888.v1Test
https://figshare.com/articles/book/The_Concise_Encyclopedia_of_Business_Ethics/24147888Test -
8دورية أكاديمية
المؤلفون: Sarah Lecinski, Jack W. Shepherd, Kate Bunting, Lara Dresser, Steven D. Quinn, Chris MacDonald, Mark C. Leake
مصطلحات موضوعية: Biophysics, molecular crowding, correlative microscopy, super-resolution, single-molecule, localization microscopy, FRET
الوصف: Compiled pdf containing 5 supplementary figures
الإتاحة: https://doi.org/10.6084/m9.figshare.21114206.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_information_from_Correlating_viscosity_and_molecular_crowding_with_fluorescent_nanobeads_and_molecular_probes_i_in_vitro_i_and_i_in_vivo_i_/21114206Test -
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المؤلفون: Chris Macdonald
المصدر: Research in Psychology and Behavioral Sciences. 11:7-11
مصطلحات موضوعية: General Medicine
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::49f18ab696e62a87569052b180e9829eTest
https://doi.org/10.12691/rpbs-11-1-2Test -
10دورية أكاديمية
المؤلفون: Lucien Jacky (10197624), Dominic Yurk (10197627), John Alvarado (10197630), Bryan Leatham (11836906), Jerrod Schwartz (11836909), John Annaloro (11836912), Chris MacDonald (836199), Aditya Rajagopal (1921924)
مصطلحات موضوعية: Biophysics, Medicine, Cell Biology, Virology, Computational Biology, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, multiple input concentrations, 432 samples contrived, standard analytical platform, positive droplet based, applications requiring ultrahigh, partition digital pcr, current dpcr assays, unique targets present, traditional dpcr thresholding, traditional dpcr, partition dpcr, positive partitions, platform ’, clinical applications, physical partition, well sensitivity, thereby limiting, theoretical analysis, substantial promise, simultaneous monitoring, simulated fractions
الوصف: Digital PCR (dPCR) is the gold-standard analytical platform for rapid high-precision quantification of genomic fragments. However, current dPCR assays are generally limited to monitoring 1–2 analytes per sample, thereby limiting the platform’s ability to address some clinical applications that require the simultaneous monitoring of 20–50 analytes per sample. Here, we present virtual-partition dPCR (VPdPCR), a novel analysis methodology enabling the detection of 10 or more target regions per color channel using conventional dPCR hardware and workflow. Furthermore, VPdPCR enables dPCR instruments to overcome upper quantitation limits caused by partitioning error. While traditional dPCR analysis establishes a single threshold to separate negative and positive partitions, VPdPCR establishes multiple thresholds to identify the number of unique targets present in each positive droplet based on fluorescence intensity. Each physical partition is then divided into a series of virtual partitions, and the resulting increase in partition count substantially decreases partitioning error. We present both a theoretical analysis of the advantages of VPdPCR and an experimental demonstration in the form of a 20-plex assay for noninvasive fetal aneuploidy testing. This demonstration assaytested on 432 samples contrived from sheared cell-line DNA at multiple input concentrations and simulated fractions of euploid or trisomy-21 “fetal” DNAis analyzed using both traditional dPCR thresholding and VPdPCR. VPdPCR analysis significantly lowers the variance of the chromosomal ratio across replicates and increases the accuracy of trisomy identification when compared to traditional dPCR, yielding > 98% single-well sensitivity and specificity. VPdPCR has substantial promise for increasing the utility of dPCR in applications requiring ultrahigh-precision quantitation.
النص الكامل 