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    Mammalian X Chromosome Dosage Compensation: Perspectives From the Germ Line.
    Bioessays 2018 May 14. Epub 2018 May 14.
    Sex Chromosome Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
    Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. Read More

    Endothelial Metabolic Control of Lymphangiogenesis.
    Bioessays 2018 May 11:e1700245. Epub 2018 May 11.
    Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, 06511, USA.
    Lymphangiogenesis is an important developmental process that is critical to regulation of fluid homeostasis, immune surveillance and response as well as pathogenesis of a number of diseases, among them cancer, inflammation, and heart failure. Specification, formation, and maturation of lymphatic blood vessels involves an interplay between a series of events orchestrated by various transcription factors that determine expression of key genes involved in lymphangiogenesis. These are traditionally thought to be under control of several key growth factors including vascular growth factor-C (VEGF-C) and fibroblast growth factors (FGFs). Read More

    Membrane Transport at an Organelle Interface in the Early Secretory Pathway: Take Your Coat Off and Stay a While: Evolution of the metazoan early secretory pathway.
    Bioessays 2018 May 9:e1800004. Epub 2018 May 9.
    Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, 440 Henry Mall, Madison, WI, 53706, USA.
    Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum-Golgi intermediate compartment (ERGIC). These membranous vesicular-tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII-coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI-dependent transport on to the cis-Golgi. Read More

    Mitochondrial Outer Membrane Channels: Emerging Diversity in Transport Processes.
    Bioessays 2018 Apr 30. Epub 2018 Apr 30.
    Biophysics, Life Sciences & Chemistry, Jacobs University Bremen, Bremen, D-28759, Germany.
    Mitochondrial function and biogenesis depend on the transport of a large variety of proteins, ions, and metabolites across the two surrounding membranes. While several specific transporters are present in the inner membrane, transport processes across the outer membrane are less understood. Recent studies reveal that the number of outer membrane channels and their transport mechanisms are more diverse than originally thought. Read More

    Normalizing Gas-Chromatography-Mass Spectrometry Data: Method Choice can Alter Biological Inference.
    Bioessays 2018 Apr 30:e1700210. Epub 2018 Apr 30.
    Wildlife Conservation Research Unit, Zoology Department, The Recanati-Kaplan Centre, University of Oxford, Tubney House, Abingdon Road, Tubney, Abingdon, OX13 5QL, UK.
    We demonstrate how different normalization techniques in GC-MS analysis impart unique properties to the data, influencing any biological inference. Using simulations, and empirical data, we compare the most commonly used techniques (Total Sum Normalization 'TSN'; Median Normalization 'MN'; Probabilistic Quotient Normalization 'PQN'; Internal Standard Normalization 'ISN'; External Standard Normalization 'ESN'; and a compositional data approach 'CODA'). When differences between biological classes are pronounced, ESN and ISN provides good results, but are less reliable for more subtly differentiated groups. Read More

    Heritable L1 Retrotransposition Events During Development: Understanding Their Origins: Examination of heritable, endogenous L1 retrotransposition in mice opens up exciting new questions and research directions.
    Bioessays 2018 Apr 30:e1700189. Epub 2018 Apr 30.
    Mater Research Institute-University of Queensland, Woolloongabba, Queensland 4102, Australia.
    The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) has played a major role in shaping the sequence composition of the mammalian genome. In our recent publication, "Heritable L1 retrotransposition in the mouse primordial germline and early embryo," we systematically assessed the rate and developmental timing of de novo, heritable endogenous L1 insertions in mice. Such heritable retrotransposition events allow L1 to exert an ongoing influence upon genome evolution. Read More

    Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries.
    Bioessays 2018 Apr 30. Epub 2018 Apr 30.
    Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
    Microautophagy is originally defined as lysosomal (vacuolar) membrane dynamics to directly enwrap and transport cytosolic components into the lumen of the lytic organelle. Molecular details of microautophagy had remained unknown until genetic studies in yeast identified a set of proteins required for the process. Subsequent studies with other experimental model organisms resulted in a series of discoveries that accompanied an expansion of the definition of microautophagy to also encompass endosomal membrane dynamics. Read More

    A Link Between Alzheimer's and Type II Diabetes Mellitus? Ca -Mediated Signal Control and Protein Localization.
    Bioessays 2018 Apr 25:e1700219. Epub 2018 Apr 25.
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
    We propose protein localization dependent signal activation (PLDSA) as a model to describe pre-existing protein partitioning between the cytosol, and membrane surface, as a means to modulate signal activation, specificity, and robustness. We apply PLDSA to explain possible molecular links between type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) by describing Ca -mediated interactions between the Src non-receptor tyrosine kinase and p52Shc adaptor protein. We suggest that these interactions may serve as a contributing factor to disease development and progression. Read More

    Novel Channels of the Outer Membrane of Mitochondria: Recent Discoveries Change Our View.
    Bioessays 2018 Apr 23:e1700232. Epub 2018 Apr 23.
    Department of Biology, University of Padova, Padua 35121, Italy.
    Ion channels mediate ion flux across biological membranes and regulate important organellar and cellular tasks. A recent study revealed the presence of four new proteins, the MIM complex (composed by Mim1 and Mim2), Ayr1, OMC7, and OMC8, that are able to form ion-conducting channels in the outer mitochondria membrane (OMM). These findings strongly indicate that the OMM is endowed with many solute-specific channels, in addition to porins and known channels mediating protein import into mitochondria. Read More

    Non-Cell Cycle Functions of the CDK Network in Ciliogenesis: Recycling the Cell Cycle Oscillator.
    Bioessays 2018 Apr 23. Epub 2018 Apr 23.
    Institut de Génétique Moléculaire de Montpellier (IGMM), University of Montpellier, CNRS 1919 Route de Mende, Montpellier, 34293, France.
    Cyclin-dependent kinases are Ser/Thr protein kinases best known for their cell cycle roles, where CDK1 triggers mitotic onset in all eukaryotes. CDKs are also involved in various other cellular processes, some of which, such as transcription and centrosome duplication, are coupled to cell cycle progression. A new study suggests that the mitotic CDK network is active at low levels in non-dividing, differentiating precursors of multiciliated cells, and that it drives ciliogenesis. Read More

    Applying iPSCs for Preserving Endangered Species and Elucidating the Evolution of Mammalian Sex Determination.
    Bioessays 2018 Apr 6:e1700152. Epub 2018 Apr 6.
    Institute of Laboratory Animals, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
    The endangered species Tokudaia osimensis has the unique chromosome constitution of 2n = 25, with an XO/XO sex chromosome configuration (2n = 25; XO). There is urgency to preserve this species and to elucidate the regulator(s) that can discriminate the males and females arising from the indistinguishable sex chromosome constitution. However, it is not realistic to examine this rare animal species by sacrificing individuals. Read More

    Ubiquitylation Pathways In Insulin Signaling and Organismal Homeostasis.
    Bioessays 2018 May 3;40(5):e1700223. Epub 2018 Apr 3.
    Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann Str. 26, 50931 Cologne, Germany.
    The insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway is a pivotal genetic program regulating cell growth, tissue development, metabolic physiology, and longevity of multicellular organisms. IIS integrates a fine-tuned cascade of signaling events induced by insulin/IGF-1, which is precisely controlled by post-translational modifications. The ubiquitin/proteasome-system (UPS) influences the functionality of IIS through inducible ubiquitylation pathways that regulate internalization of the insulin/IGF-1 receptor, the stability of downstream insulin/IGF-1 signaling targets, and activity of nuclear receptors for control of gene expression. Read More

    How Does a Helicase Unwind DNA? Insights from RecBCD Helicase.
    Bioessays 2018 Mar 30. Epub 2018 Mar 30.
    Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, School of Medicine, St. Louis, MO, 63110, USA.
    DNA helicases are a class of molecular motors that catalyze processive unwinding of double stranded DNA. In spite of much study, we know relatively little about the mechanisms by which these enzymes carry out the function for which they are named. Most current views are based on inferences from crystal structures. Read More

    Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past.
    Bioessays 2018 May 30;40(5):e1700246. Epub 2018 Mar 30.
    Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY 10024, USA.
    The Hawaiian Drosophila have been a model system for evolutionary, ecological, and ethological studies since the inception of the Hawaiian Drosophila Project in the 1960s. Here we review the past and present research on this incredible lineage and provide a prospectus for future directions on genomics and microbial interactions. While the number of publications on this group has waxed and waned over the years, we assert that recent systematic, biogeographic, and ecological studies have reinvigorated Hawaiian Drosophila as an evolutionary model system. Read More

    New Roles for the Nucleolus in Health and Disease.
    Bioessays 2018 May 30;40(5):e1700233. Epub 2018 Mar 30.
    ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Acton, 2601, Australia.
    Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for dysregulation in many human diseases; in some cases, independent of its functions in ribosome biogenesis. Read More

    BET-ting on Nrf2: How Nrf2 Signaling can Influence the Therapeutic Activities of BET Protein Inhibitors.
    Bioessays 2018 May 30;40(5):e1800007. Epub 2018 Mar 30.
    Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
    BET proteins such as Brd3 and Brd4 are chromatin-associated factors, which control gene expression programs that promote inflammation and cancer. The Nrf2 transcription factor is a master regulator of genes that protect the organism against xenobiotic attack and oxidative stress. Nrf2 has demonstrated anti-inflammatory activity and can support cancer cell malignancy. Read More

    Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.
    Bioessays 2018 May 30;40(5):e1700240. Epub 2018 Mar 30.
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Read More

    DNA Repair: The Search for Homology.
    Bioessays 2018 May 30;40(5):e1700229. Epub 2018 Mar 30.
    Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
    The repair of chromosomal double-strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51-mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms. Read More

    Demarcation of Viral Shelters Results in Destruction by Membranolytic GTPases: Antiviral Function of Autophagy Proteins and Interferon-Inducible GTPases.
    Bioessays 2018 Mar 30:e1700231. Epub 2018 Mar 30.
    Committee on Immunology, The University of Chicago, Chicago, IL, 60637, USA.
    A hallmark of positive-sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti-microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune-defense mechanism against disparate vacuolar pathogens. Read More

    Multi-Invasion-Induced Rearrangements as a Pathway for Physiological and Pathological Recombination.
    Bioessays 2018 May 26;40(5):e1700249. Epub 2018 Mar 26.
    Department of Microbiology and Molecular Genetics, One Shields Avenue, University of California, Davis, CA, 95616, USA.
    Cells mitigate the detrimental consequences of DNA damage on genome stability by attempting high fidelity repair. Homologous recombination templates DNA double-strand break (DSB) repair on an identical or near identical donor sequence in a process that can in principle access the entire genome. Other physiological processes, such as homolog recognition and pairing during meiosis, also harness the HR machinery using programmed DSBs to physically link homologs and generate crossovers. Read More

    A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?: Brain tumors and microcephaly arise from opposing derangements regulating progenitor growth. Drivers of microcephaly could be attractive brain tumor targets.
    Bioessays 2018 May 26;40(5):e1700243. Epub 2018 Mar 26.
    Department of Neurology, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.
    New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Read More

    The Diversification of Early Emerging Metazoans: A Window into the Evolution of Animal Multicellularity.
    Bioessays 2018 May 25;40(5):e1800029. Epub 2018 Mar 25.
    Department of Molecular Evolution and Development, University of Vienna, Vienna, 1090, Austria.
    The biannual international workshop entitled "The diversification of early emerging metazoans: A window into animal evolution?" took place at the Evangelische Akademie Tutzing, Germany, 11-14. September 2017. It was organized by Thomas Bosch (Kiel), Thomas Holstein (Heidelberg), and Ulrich Technau (Vienna), and it was sponsored by the Deutsche Forschungsgemeinschaft (DFG). Read More

    An Emerging Group of Membrane Property Sensors Controls the Physical State of Organellar Membranes to Maintain Their Identity.
    Bioessays 2018 May 25;40(5):e1700250. Epub 2018 Mar 25.
    Medical Faculty, Department of Medical Biochemistry and Molecular Bioloy, Saarland University, 66421 Homburg, Germany.
    The biological membranes of eukaryotic cells harbor sensitive surveillance systems to establish, sense, and maintain characteristic physicochemical properties that ultimately define organelle identity. They are fundamentally important for membrane homeostasis and play active roles in cellular signaling, protein sorting, and the formation of vesicular carriers. Here, we compare the molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of fatty acid desaturation and the response to unfolded proteins and lipid bilayer stress in order to identify their commonalities and specializations. Read More

    Identifying Human Naïve Pluripotent Stem Cells - Evaluating State-Specific Reporter Lines and Cell-Surface Markers.
    Bioessays 2018 May 25;40(5):e1700239. Epub 2018 Mar 25.
    Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
    Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re-evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed 'naïve' human pluripotent stem cells to distinguish them from the conventional 'primed' cells. Read More

    Demystifying Eukaryote Lateral Gene Transfer (Response to Martin 2017 DOI: 10.1002/bies.201700115).
    Bioessays 2018 May 15;40(5):e1700242. Epub 2018 Mar 15.
    Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, P.O. Box 15000, Halifax, CAN B3H 4R2, Nova Scotia, Canada.
    In a recent BioEssays paper [W. F. Martin, BioEssays 2017, 39, 1700115], William Martin sharply criticizes evolutionary interpretations that involve lateral gene transfer (LGT) into eukaryotic genomes. Read More

    Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation.
    Bioessays 2018 Apr 9;40(4):e1700135. Epub 2018 Mar 9.
    Prof. Dr. O. J. Gruss, Institute of Genetics, University of Bonn, Karlrobert-Kreiten-Str.13, 53115 Bonn, Germany.
    Centrosomes are the main microtubule organizing centers in animal cells. In particular during embryogenesis, they ensure faithful spindle formation and proper cell divisions. As metazoan centrosomes are eliminated during oogenesis, they have to be reassembled upon fertilization. Read More

    How Polycomb-Mediated Cell Memory Deals With a Changing Environment: Variations in PcG complexes and proteins assortment convey plasticity to epigenetic regulation as a response to environment.
    Bioessays 2018 Apr 9;40(4):e1700137. Epub 2018 Mar 9.
    King Abdullah University of Science and Technology (KAUST), Environmental Epigenetics Research Program, Biological and Environmental Sciences and Engineering Division, Thuwal 23955-6900, Saudi Arabia.
    Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes. In evolution the complexity of this system have increased, particularly in vertebrates, indicating combinatorial and dynamic properties of Polycomb proteins, in some cases even overflowing outside the cell nucleus. Read More

    Integrity of IKK/NF-κB Shields Thymic Stroma That Suppresses Susceptibility to Autoimmunity, Fungal Infection, and Carcinogenesis.
    Bioessays 2018 Apr 9;40(4):e1700131. Epub 2018 Mar 9.
    Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, 21701, Maryland, USA.
    A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell-mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α (IKKα) is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic epithelial cells (mTECs) that facilitate the deletion of autoreactive T cells in the thymus. Read More

    Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis: Re-Examining Lipoprotein Transport Mechanisms Among Diverse Gram-Negative Bacteria While Exploring New Discoveries and Questions.
    Bioessays 2018 Apr 7;40(4):e1700187. Epub 2018 Mar 7.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
    The Gram-negative outer membrane (OM) is a potent permeability barrier against antibiotics, limiting clinical options amid mounting rates of resistance. The Lol transport pathway delivers lipoproteins to the OM. All the OM assembly machines require one or more OM lipoprotein to function, making the Lol pathway central for all aspects of OM biogenesis. Read More

    Microbial Diversity in the Eukaryotic SAR Clade: Illuminating the Darkness Between Morphology and Molecular Data.
    Bioessays 2018 Apr 7;40(4):e1700198. Epub 2018 Mar 7.
    Department of Biological Sciences, Smith College, Northampton, MA 01063, USA.
    Despite their diversity and ecological importance, many areas of the SAR-Stramenopila, Alveolata, and Rhizaria-clade are poorly understood as the majority (90%) of SAR species lack molecular data and only 5% of species are from well-sampled families. Here, we review and summarize the state of knowledge about the three major clades of SAR, describing the diversity within each clade and identifying synapomorphies when possible. We also assess the "dark area" of SAR: the morphologically described species that are missing molecular data. Read More

    Active Sleep Promotes Functional Connectivity in Developing Sensorimotor Networks.
    Bioessays 2018 Apr 6;40(4):e1700234. Epub 2018 Mar 6.
    Department of Psychological and Brain Sciences, University of Iowa, Iowa City, 52242, Iowa, USA.
    A ubiquitous feature of active (REM) sleep in mammals and birds is its relative abundance in early development. In rat pups across the first two postnatal weeks, active sleep promotes the expression of synchronized oscillatory activity within and between cortical and subcortical sensorimotor structures. Sensory feedback from self-generated myoclonic twitches - which are produced exclusively during active sleep - also triggers neural oscillations in those structures. Read More

    The Rise of the Cartwheel: Seeding the Centriole Organelle.
    Bioessays 2018 Apr 6;40(4):e1700241. Epub 2018 Mar 6.
    School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
    The cartwheel is a striking structure critical for building the centriole, a microtubule-based organelle fundamental for organizing centrosomes, cilia, and flagella. Over the last 50 years, the cartwheel has been described in many systems using electron microscopy, but the molecular nature of its constituent building blocks and their assembly mechanisms have long remained mysterious. Here, we review discoveries that led to the current understanding of cartwheel structure, assembly, and function. Read More

    DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond.
    Bioessays 2018 Apr 5;40(4):e1700235. Epub 2018 Mar 5.
    ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, ACT 2600, Canberra City, Australia.
    Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. Read More

    Replicating and Cycling Stores of Information Perpetuate Life.
    Bioessays 2018 Apr 1;40(4):e1700161. Epub 2018 Mar 1.
    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
    Life is perpetuated through a single-cell bottleneck between generations in many organisms. Here, I highlight that this cell holds information in two distinct stores: in the linear DNA sequence that is replicated during cell divisions, and in the three-dimensional arrangement of molecules that can change during development but is recreated at the start of each generation. These two interdependent stores of information - one replicating with each cell division and the other cycling with a period of one generation - coevolve while perpetuating an organism. Read More

    Advances in Structural Biology and the Application to Biological Filament Systems.
    Bioessays 2018 Apr 27;40(4):e1700213. Epub 2018 Feb 27.
    Institute of Molecular and Cell Biology A*STAR (Agency for Science, Technology and Research) Biopolis, Singapore 138673, Singapore.
    Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources (microfocus synchrotron beamlines and free electron lasers) and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. Read More

    PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery.
    Bioessays 2018 Apr 23;40(4):e1700247. Epub 2018 Feb 23.
    Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, 310003 Hangzhou, China.
    Proteolysis-targeting chimeric molecules (PROTACs) represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero-bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Read More

    Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer.
    Bioessays 2018 Mar 15;40(3). Epub 2018 Feb 15.
    Centre for Integrative Ecology School of Life and Environmental Sciences Deakin University, Waurn Ponds, Victoria, 3218, Australia.
    Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease (DFTD), a transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii), provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts. Read More

    Cytosolic N-Glycans: Triggers for Ubiquitination Directing Proteasomal and Autophagic Degradation: Molecular Systems for Monitoring Cytosolic N-Glycans as Signals for Unwanted Proteins and Organelles.
    Bioessays 2018 Mar 13;40(3). Epub 2018 Feb 13.
    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
    Proteins on the cell surface and secreted proteins are modified with sugar chains that generate and modulate biological complexity and diversity. Sugar chains not only contribute physically to the conformation and solubility of proteins, but also exert various functions via sugar-binding proteins (lectins) that reside on the cell surface or in organelles of the secretory pathway. However, some glycosidases and lectins are found in the cytosol or nucleus. Read More

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