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Medicine, Department of

The University of Alberta’s Department of Medicine is a recognized leader in innovative education, world-class research and outstanding patient care. We are the largest department in the Faculty of Medicine & Dentistry and the biggest at the University of Alberta. More than 800 academic and clinical faculty, students, residents and fellows help achieve our goal of improving health and health care locally and globally. These efforts are supported by more than 300 health, technical and support staff.
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  1. Concomitant loss of NDH complex‐related genes within chloroplast and nuclear genomes in some orchids [Download]

    Title: Concomitant loss of NDH complex‐related genes within chloroplast and nuclear genomes in some orchids
    Creator: Choun‐Sea Lin
    Description: The chloroplast NAD(P)H dehydrogenase-like (NDH) complex consists of about 30 subunits from both the nuclear and chloroplast genomes and is ubiquitous across most land plants. In some orchids, such as Phalaenopsis equestris, Dendrobium officinale and Dendrobium catenatum, most of the 11 chloroplast genome-encoded ndh genes (cp-ndh) have been lost. Here we investigated whether functional cp-ndh genes have been completely lost in these orchids or whether they have been transferred and retained in the nuclear genome. Further, we assessed whether both cp-ndh genes and nucleus-encoded NDH-related genes can be lost, resulting in the absence of the NDH complex. Comparative analyses of the genome of Apostasia odorata, an orchid species with a complete complement of cp-ndh genes which represents the sister lineage to all other orchids, and three published orchid genome sequences for P. equestris, D. officinale and D. catenatum, which are all missing cp-ndh genes, indicated that copies of cp-ndh genes are not present in any of these four nuclear genomes. This observation suggests that the NDH complex is not necessary for some plants. Comparative genomic/transcriptomic analyses of currently available plastid genome sequences and nuclear transcriptome data showed that 47 out of 660 photoautotrophic plants and all the heterotrophic plants are missing plastid-encoded cp-ndh genes and exhibit no evidence for maintenance of a functional NDH complex. Our data indicate that the NDH complex can be lost in photoautotrophic plant species. Further, the loss of the NDH complex may increase the probability of transition from a photoautotrophic to a heterotrophic life history.
    Subjects: chloroplast NAD(P)H dehydrogenase-like (NDH) complex
    Date Created: 2017/04/11
  2. Evolution of strigolactone receptors by gradual neo-functionalization of KAI2 paralogues [Download]

    Title: Evolution of strigolactone receptors by gradual neo-functionalization of KAI2 paralogues
    Creator: Rohan Bythell-Douglas,
    Description: Background: Strigolactones (SLs) are a class of plant hormones that control many aspects of plant growth. The SL signalling mechanism is homologous to that of karrikins (KARs), smoke-derived compounds that stimulate seed germination. In angiosperms, the SL receptor is an α/β-hydrolase known as DWARF14 (D14); its close homologue, KARRIKIN INSENSITIVE2 (KAI2), functions as a KAR receptor and likely recognizes an uncharacterized, endogenous signal (‘KL’). Previous phylogenetic analyses have suggested that the KAI2 lineage is ancestral in land plants, and that canonical D14-type SL receptors only arose in seed plants; this is paradoxical, however, as non-vascular plants synthesize and respond to SLs. Results: We have used a combination of phylogenetic and structural approaches to re-assess the evolution of the D14/KAI2 family in land plants. We analysed 339 members of the D14/KAI2 family from land plants and charophyte algae. Our phylogenetic analyses show that the divergence between the eu-KAI2 lineage and the DDK (D14/DLK2/ KAI2) lineage that includes D14 occurred very early in land plant evolution. We show that eu-KAI2 proteins are highly conserved, and have unique features not found in DDK proteins. Conversely, we show that DDK proteins show considerable sequence and structural variation to each other, and lack clearly definable characteristics. We use homology modelling to show that the earliest members of the DDK lineage structurally resemble KAI2 and that SL receptors in non-seed plants likely do not have D14-like structure. We also show that certain groups of DDK proteins lack the otherwise conserved MORE AXILLARY GROWTH2 (MAX2) interface, and may thus function independently of MAX2, which we show is highly conserved throughout land plant evolution. Conclusions: Our results suggest that D14-like structure is not required for SL perception, and that SL perception has relatively relaxed structural requirements compared to KAI2-mediated signalling. We suggest that SL perception gradually evolved by neo-functionalization within the DDK lineage, and that the transition from KAI2-like to D14-like protein may have been driven by interactions with protein partners, rather than being required for SL perception per se.
    Subjects: Strigolactone signalling, Strigolactone evolution, Phylogenetics, Neo-functionalization
    Date Created: 2017/06/29
  3. Modeling the Colchicum autumnale Tubulin and a Comparison of Its Interaction with Colchicine to Human Tubulin [Download]

    Title: Modeling the Colchicum autumnale Tubulin and a Comparison of Its Interaction with Colchicine to Human Tubulin
    Creator: Spasevska, Ivana
    Description: Tubulin is the target for many small-molecule natural compounds, which alter microtubules dynamics, and lead to cell cycle arrest and apoptosis. One of these compounds is colchicine, a plant alkaloid produced by Colchicum autumnale. While C. autumnale produces a potent cytotoxin, colchicine, and expresses its target protein, it is immune to colchicine’s cytotoxic action and the mechanism of this resistance is hitherto unknown. In the present paper, the molecular mechanisms responsible for colchicine resistance in C. autumnale are investigated and compared to human tubulin. To this end, homology models for C. autumnale α-β tubulin heterodimer are created and molecular dynamics (MD) simulations together with molecular mechanics Poisson–Boltzmann calculations (MM/PBSA) are performed to determine colchicine’s binding affinity for tubulin. Using our molecular approach, it is shown that the colchicine-binding site in C. autumnale tubulin contains a small number of amino acid substitutions compared to human tubulin. However, these substitutions induce significant reduction in the binding affinity for tubulin, and subsequently fewer conformational changes in its structure result. It is suggested that such small conformational changes are insufficient to profoundly disrupt microtubule dynamics, which explains the high resistance to colchicine by C. autumnale
    Subjects: tubulin, colchicine, C. autumnale, binding site, cytotoxicity, molecular modeling
    Date Created: 2017/08/02
  4. Rheumatology

    Title: Rheumatology
    Creator: ERA Administrator
  5. Antimalarials for treating rheumatoid arthritis [Download]

    Title: Antimalarials for treating rheumatoid arthritis
    Creator: Suarez-Almazor ME
    Subjects: Randomized Controlled Trials as Topic, Arthritis, Rheumatoid, Antimalarials, Controlled Clinical Trials as Topic
    Date Created: 2000
  6. General Internal Medicine

    Title: General Internal Medicine
    Creator: ERA Administrator