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    Single Pair Förster Resonance Energy Transfer: A Versatile Tool To Investigate Protein Conformational Dynamics.
    Bioessays 2018 Jan 5. Epub 2018 Jan 5.
    Department Chemie, Center for Nanoscience (CeNS), Center for Integrated Protein Science Munich (CIPSM), Nanosystem Initiative Munich (NIM), Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany.
    Conformational changes of proteins and other biomolecules play a fundamental role in their functional mechanism. Single pair Förster resonance energy transfer (spFRET) offers the possibility to detect these conformational changes and dynamics, and to characterize their underlying kinetics. Using spFRET on microscopes with different modes of detection, dynamic timescales ranging from nanoseconds to seconds can be quantified. Read More

    Analyzing Horizontal Transfer of Transposable Elements on a Large Scale: Challenges and Prospects.
    Bioessays 2017 Dec 28. Epub 2017 Dec 28.
    UMR CNRS 9191, UMR 247 IRD Laboratoire Evolution, Génomes, Comportement, Écologie, Université Paris-Sud,, 91198 Gif-sur-Yvette, France.
    Whoever compares the genomes of distantly related species might find aberrantly high sequence similarity at certain loci. Such anomaly can only be explained by genetic material being transferred through other means than reproduction, that is, a horizontal transfer (HT). Between multicellular organisms, the transferred material will likely turn out to be a transposable element (TE). Read More

    Cell Size Control via an Unstable Accumulating Activator and the Phenomenon of Excess Mitotic Delay.
    Bioessays 2017 Dec 28. Epub 2017 Dec 28.
    Prof. N. Rhind, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
    Unstable Accumulating Activator models for cellular size control propose an activator that accumulates in a size-dependent manner and triggers cell cycle progression once it has reached a certain threshold. Having a short half life makes such an activator responsive to changes in cell size and makes specific predictions for how cells respond to perturbation. In particular, it explains the curious phenomenon of excess mitotic delay. Read More

    Noise in the Machine: Alternative Pathway Sampling is the Rule During DNA Replication.
    Bioessays 2017 Dec 28. Epub 2017 Dec 28.
    Structure and Dynamics of Molecular Machines, Max Planck Institute of Biochemistry, Martinsried, Germany.
    The astonishing efficiency and accuracy of DNA replication has long suggested that refined rules enforce a single highly reproducible sequence of molecular events during the process. This view was solidified by early demonstrations that DNA unwinding and synthesis are coupled within a stable molecular factory, known as the replisome, which consists of conserved components that each play unique and complementary roles. However, recent single-molecule observations of replisome dynamics have begun to challenge this view, revealing that replication may not be defined by a uniform sequence of events. Read More

    Transmembrane Signal Transduction in Two-Component Systems: Piston, Scissoring, or Helical Rotation?
    Bioessays 2017 Dec 27. Epub 2017 Dec 27.
    Moscow Institute of Physics and Technology, 141700, Dolgoprudniy, Russia.
    Allosteric and transmembrane (TM) signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. Read More

    When MicroRNAs Meet RNA Editing in Cancer: A Nucleotide Change Can Make a Difference.
    Bioessays 2017 Dec 27. Epub 2017 Dec 27.
    Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA.
    RNA editing is a major post-transcriptional mechanism that changes specific nucleotides at the RNA level. The most common RNA editing type in humans is adenosine (A) to inosine (I) editing, which is mediated by ADAR enzymes. RNA editing events can not only change amino acids in proteins, but also affect the functions of non-coding RNAs such as miRNAs. Read More

    The Many Roles of Type II Phosphatidylinositol 4-Kinases in Membrane Trafficking: New Tricks for Old Dogs.
    Bioessays 2017 Dec 27. Epub 2017 Dec 27.
    Lipid and Membrane Biology Group, UCL Division of Medicine, Royal Free Campus, University College London, London, NW3 2PF, UK.
    The type II phosphatidylinositol 4-kinases (PI4KIIs) produce the lipid phosphatidylinositol 4-phosphate (PtdIns4P) and participate in a confusing variety of membrane trafficking and signaling roles. This review argues that both historical and contemporary evidence supports the function of the PI4KIIs in numerous trafficking pathways, and that the key to understanding the enzymatic regulation is through membrane interaction and the intrinsic membrane environment. By summarizing new research and examining the trafficking roles of the PI4KIIs in the context of recently solved molecular structures, I highlight how mechanisms of PI4KII function and regulation are providing insights into the development of cancer and in neurological disease. Read More

    Microbiome-Germline Interactions and Their Transgenerational Implications.
    Bioessays 2017 Dec 21. Epub 2017 Dec 21.
    Biomolecular Sciences, Rehovot, Israel.
    It is becoming increasingly clear that most, if not all, animals and plants are associated with a diverse array of resident gut microbiota. This symbiosis is regulated by host-microbiome interactions which influence the development, homeostasis, adaptation and evolution of the host. Recent evidence indicated that these interactions can also affect the host germline and have a potential of supporting transgenerational effects, including inheritance of acquired characteristics. Read More

    RNase III Nucleases and the Evolution of Antiviral Systems.
    Bioessays 2017 Dec 21. Epub 2017 Dec 21.
    Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA.
    Every living entity requires the capacity to defend against viruses in some form. From bacteria to plants to arthropods, cells retain the capacity to capture genetic material, process it in a variety of ways, and subsequently use it to generate pathogen-specific small RNAs. These small RNAs can then be used to provide specificity to an otherwise non-specific nuclease, generating a potent antiviral system. Read More

    Epigenetic and Transcriptional Variability Shape Phenotypic Plasticity.
    Bioessays 2017 Dec 18. Epub 2017 Dec 18.
    MRC/BHF Cardiovascular Epidemiology Unit Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Read More

    The Wnt Transcriptional Switch: TLE Removal or Inactivation?
    Bioessays 2017 Dec 18. Epub 2017 Dec 18.
    Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109-1048.
    Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Read More

    RNA Decay Factor UPF1 Promotes Protein Decay: A Hidden Talent.
    Bioessays 2018 Jan 13;40(1). Epub 2017 Dec 13.
    Department of Reproductive Medicine, University of California San Diego, La Jolla, CA, 92093-0695, USA.
    The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay (NMD) pathway. Feng et al. now report a new function for UPF1-it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. Read More

    Combing Chromosomal DNA Mediated by the SMC Complex: Structure and Mechanisms.
    Bioessays 2017 Dec 11. Epub 2017 Dec 11.
    Department of Biology, University of York, York, YO10 5DD, UK.
    Genome maintenance requires various nucleoid-associated factors in prokaryotes. Among them, the SMC (Structural Maintenance of Chromosomes) protein has been thought to play a static role in the organization and segregation of the chromosome during cell division. However, recent studies have shown that the bacterial SMC is required to align left and right arms of the emerging chromosome and that the protein dynamically travels from origin to Ter region. Read More

    It Is Time to Re-Evaluate the Peer Review Process for Preclinical Research.
    Bioessays 2018 Jan 11;40(1). Epub 2017 Dec 11.
    Department of Surgical Oncology The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    Problems in peer review, the backbone of maintaining high standards in scientific publishing, have led to wide spread discontent within the scientific community. Training in the peer review process and a simpler format to assist in decision making are possible courses to improve and expedite the process of peer review and scientific publishing. Read More

    Evolution Is Linear: Debunking Life's Little Joke.
    Bioessays 2018 Jan 6;40(1). Epub 2017 Dec 6.
    Department of Life Sciences, The Natural History Museum, Cromwell Road, SW7 5BD London, UK.
    Linear depictions of the evolutionary process are ubiquitous in popular culture, but linear evolutionary imagery is strongly rejected by scientists who argue that evolution branches. This point is frequently illustrated by saying that we didn't evolve from monkeys, but that we are related to them as collateral relatives. Yet, we did evolve from monkeys, but our monkey ancestors are extinct, not extant. Read More

    Transposable Element Mediated Innovation in Gene Regulatory Landscapes of Cells: Re-Visiting the "Gene-Battery" Model.
    Bioessays 2018 Jan 5;40(1). Epub 2017 Dec 5.
    Department of Genetics Center for Genome Sciences and Systems Biology Washington University School of Medicine, St Louis, MO, 63110, USA.
    Transposable elements (TEs) are no longer considered to be "junk" DNA. Here, we review how TEs can impact gene regulation systematically. TEs encode various regulatory elements that enables them to regulate gene expression. Read More

    mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.
    Bioessays 2018 Jan 4;40(1). Epub 2017 Dec 4.
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.
    Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Read More

    Ca2+ -Dependent Hyperpolarization Pathways in Sleep Homeostasis and Mental Disorders.
    Bioessays 2018 Jan 4;40(1). Epub 2017 Dec 4.
    Dr. S. Shi, Prof. H. R. Ueda, Department of Systems Pharmacology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
    Although we are beginning to understand the neuronal and biochemical nature of sleep regulation, questions remain about how sleep is homeostatically regulated. Beyond its importance in basic physiology, understanding sleep may also shed light on psychiatric and neurodevelopmental disorders. Recent genetic studies in mammals revealed several non-secretory proteins that determine sleep duration. Read More

    Soft-Bodied Fossils Are Not Simply Rotten Carcasses - Toward a Holistic Understanding of Exceptional Fossil Preservation: Exceptional Fossil Preservation Is Complex and Involves the Interplay of Numerous Biological and Geological Processes.
    Bioessays 2018 Jan 29;40(1). Epub 2017 Nov 29.
    School of Earth Sciences, University of Bristol, Wills Memorial Building, Queen's Road, Bristol, BS8 1RJ, UK.
    Exceptionally preserved fossils are the product of complex interplays of biological and geological processes including burial, autolysis and microbial decay, authigenic mineralization, diagenesis, metamorphism, and finally weathering and exhumation. Determining which tissues are preserved and how biases affect their preservation pathways is important for interpreting fossils in phylogenetic, ecological, and evolutionary frameworks. Although laboratory decay experiments reveal important aspects of fossilization, applying the results directly to the interpretation of exceptionally preserved fossils may overlook the impact of other key processes that remove or preserve morphological information. Read More

    Unmodern Synthesis: Developmental Hierarchies and the Origin of Phenotypes.
    Bioessays 2018 Jan 27;40(1). Epub 2017 Nov 27.
    Department of Biology, Duke University 130 Science Dr., Durham, NC, 27708, USA.
    The question of whether the modern evolutionary synthesis requires an extension has recently become a topic of discussion, and a source of controversy. We suggest that this debate is, for the most part, not about the modern synthesis at all. Rather, it is about the extent to which genetic mechanisms can be regarded as the primary determinants of phenotypic characters. Read More

    Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?
    Bioessays 2018 Jan 23;40(1). Epub 2017 Nov 23.
    Epidemiology Research Group, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven, Belgium.
    What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this be translated to humans? To date, literature on fathers is scarce. Read More

    The Wisdom of Networks: A General Adaptation and Learning Mechanism of Complex Systems: The Network Core Triggers Fast Responses to Known Stimuli; Innovations Require the Slow Network Periphery and Are Encoded by Core-Remodeling.
    Bioessays 2018 Jan 23;40(1). Epub 2017 Nov 23.
    Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
    I hypothesize that re-occurring prior experience of complex systems mobilizes a fast response, whose attractor is encoded by their strongly connected network core. In contrast, responses to novel stimuli are often slow and require the weakly connected network periphery. Upon repeated stimulus, peripheral network nodes remodel the network core that encodes the attractor of the new response. Read More

    The PIWI-Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells.
    Bioessays 2018 Jan 22;40(1). Epub 2017 Nov 22.
    Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, 113-0032, Japan.
    The PIWI-interacting RNA (piRNA) pathway, one of the major eukaryotic small RNA silencing pathways, is a genome surveillance system that silences selfish genes in animal gonads. piRNAs guide PIWI protein to target genes through Watson-Crick RNA-RNA base-parings. Loss of piRNA function causes genome instability, inducing failure in gametogenesis and infertility. Read More

    CIN and Aneuploidy: Different Concepts, Different Consequences.
    Bioessays 2018 Jan 21;40(1). Epub 2017 Nov 21.
    European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
    Chromosomal instability (CIN) and aneuploidy are similar concepts but not synonymous. CIN is the process that leads to chromosome copy number alterations, and aneuploidy is the result. While CIN and resulting aneuploidy often cause growth defects, they are also selected for in cancer cells. Read More

    Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling.
    Bioessays 2018 Jan 17;40(1). Epub 2017 Nov 17.
    APC Microbiome Institute, University College Cork, Cork, Ireland.
    The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. Read More

    Gravity Constraints Drive Biological Systems Toward Specific Organization Patterns: Commitment of cell specification is constrained by physical cues.
    Bioessays 2018 Jan 14;40(1). Epub 2017 Nov 14.
    Department of Surgery "PietroValdoni", Sapienza University of Rome, via A. Scarpa 14, Rome 00161, Italy.
    Different cell lineages growing in microgravity undergo a spontaneous transition leading to the emergence of two distinct phenotypes. By returning these populations in a normal gravitational field, the two phenotypes collapse, recovering their original configuration. In this review, we hypothesize that, once the gravitational constraint is removed, the system freely explores its phenotypic space, while, when in a gravitational field, cells are "constrained" to adopt only one favored configuration. Read More

    Too Much Eukaryote LGT.
    Bioessays 2017 Dec 25;39(12). Epub 2017 Oct 25.
    University of Düsseldorf, Universitätsstr. 1, Düsseldorf 40225, Germany.
    The realization that prokaryotes naturally and frequently disperse genes across steep taxonomic boundaries via lateral gene transfer (LGT) gave wings to the idea that eukaryotes might do the same. Eukaryotes do acquire genes from mitochondria and plastids and they do transfer genes during the process of secondary endosymbiosis, the spread of plastids via eukaryotic algal endosymbionts. From those observations it, however, does not follow that eukaryotes transfer genes either in the same ways as prokaryotes do, or to a quantitatively similar degree. Read More

    Linking Mitochondria and Synaptic Transmission: The CB1 Receptor.
    Bioessays 2017 Dec 23;39(12). Epub 2017 Oct 23.
    Department of Biology, Université de Moncton, 18 Av Antonine Maillet, Moncton, New Brunswick, Canada.
    CB1 receptors are functionally present within brain mitochondria (mtCB1), although they are usually considered specifically targeted to plasma membrane. Acute activation of mtCB1 alters mitochondrial ATP generation, synaptic transmission, and memory performance. However, the detailed mechanism linking disrupted mitochondrial metabolism and synaptic transmission is still uncharacterized. Read More

    Broad Chromatin Domains: An Important Facet of Genome Regulation.
    Bioessays 2017 Dec 23;39(12). Epub 2017 Oct 23.
    The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
    Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans. Read More

    Animal Models in Translational Research: Rosetta Stone or Stumbling Block?
    Bioessays 2017 Dec 20;39(12). Epub 2017 Oct 20.
    Department of Biological Sciences, University of New Hampshire, Durham, NH, USA.
    Leading animal models are powerful tools for translational research, but they also present obstacles. Poorly conducted preclinical research in animals is a common cause of translational failure, but even when such research is well-designed and carefully executed, challenges remain. In particular, dominant models may bias research directions, elide essential aspects of human disease, omit important context, or subtly shift research targets. Read More

    Crowd-Sourcing of Membrane Fission: How crowding of non-specialized membrane-bound proteins contributes to cellular membrane fission.
    Bioessays 2017 Dec 20;39(12). Epub 2017 Oct 20.
    Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75013, Paris, France.
    Fission of cellular membranes is ubiquitous and essential for life. Complex protein machineries, such as the dynamin and ESCRT spirals, have evolved to mediate membrane fission during diverse cellular processes, for example, vesicle budding. A new study suggests that non-specialized membrane-bound proteins can induce membrane fission through mass action due to protein crowding. Read More

    Untranslated Parts of Genes Interpreted: Making Heads or Tails of High-Throughput Transcriptomic Data via Computational Methods: Computational methods to discover and quantify isoforms with alternative untranslated regions.
    Bioessays 2017 Dec 20;39(12). Epub 2017 Oct 20.
    Institute of Structural and Molecular Biology, Department of Biological Sciences Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
    In this review we highlight the importance of defining the untranslated parts of transcripts, and present a number of computational approaches for the discovery and quantification of alternative transcription start and poly-adenylation events in high-throughput transcriptomic data. The fate of eukaryotic transcripts is closely linked to their untranslated regions, which are determined by the position at which transcription starts and ends at a genomic locus. Although the extent of alternative transcription starts and alternative poly-adenylation sites has been revealed by sequencing methods focused on the ends of transcripts, the application of these methods is not yet widely adopted by the community. Read More

    Science: How the Status Quo Harms its Cultural Authority.
    Bioessays 2017 Dec 16;39(12). Epub 2017 Oct 16.
    School of Natural and Built Environments, University of South Australia, Mawson Lakes, South Australia, 5095, Australia.
    Three distinct explanatory models are described which underpin the relationship between the cultural authority of science and public trust. This essay describes how current discourses framed around how the enterprise of science is undertaken; damage these models, diminishing knowledge-attitudes, alienating the public while reducing the cultural meaning of science. Read More

    How Communication Between Nucleosomes Enables Spreading and Epigenetic Memory of Histone Modifications.
    Bioessays 2017 Dec 16;39(12). Epub 2017 Oct 16.
    Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.
    Nucleosomes "talk" to each other about their modification state to form extended domains of modified histones independently of the underlying DNA sequence. At the same time, DNA elements promote modification of nucleosomes in their vicinity. How do these site-specific and histone-based activities act together to regulate spreading of histone modifications along the genome? How do they enable epigenetic memory to preserve cell identity? Many models for the dynamics of repressive histone modifications emphasize the role of strong positive feedback loops, which reinforce histone modifications by recruiting histone modifiers to preexisting modifications. Read More

    The Function of the Golgi Ribbon Structure - An Enduring Mystery Unfolds!
    Bioessays 2017 Nov 6;39(11). Epub 2017 Oct 6.
    The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, 3010, Australia.
    The Golgi apparatus in vertebrate cells consists of individual Golgi stacks fused together in a continuous ribbon structure. The ribbon structure per se is not required to mediate the classical functions of this organelle and the relevance of the "ribbon" structure has been a mystery since first identified ultrastructurally in the 1950s. Recent advances recognize a role for the Golgi apparatus in a range of cellular processes, some mediated by signaling networks which are regulated at the Golgi. Read More

    Ecological and Evolutionary Benefits of Temperate Phage: What Does or Doesn't Kill You Makes You Stronger.
    Bioessays 2017 Dec 6;39(12). Epub 2017 Oct 6.
    Department of Animal and Plant Sciences, University of Sheffield, Alfred Denny Building, Sheffield, UK.
    Infection by a temperate phage can lead to death of the bacterial cell, but sometimes these phages integrate into the bacterial chromosome, offering the potential for a more long-lasting relationship to be established. Here we define three major ecological and evolutionary benefits of temperate phage for bacteria: as agents of horizontal gene transfer (HGT), as sources of genetic variation for evolutionary innovation, and as weapons of bacterial competition. We suggest that a coevolutionary perspective is required to understand the roles of temperate phages in bacterial populations. Read More

    How and Why to Build a Unified Tree of Life.
    Bioessays 2017 Nov 5;39(11). Epub 2017 Oct 5.
    Ottawa, ON, Canada.
    Phylogenetic trees are a crucial backbone for a wide breadth of biological research spanning systematics, organismal biology, ecology, and medicine. In 2015, the Open Tree of Life project published a first draft of a comprehensive tree of life, summarizing digitally available taxonomic and phylogenetic knowledge. This paper reviews, investigates, and addresses the following questions as a follow-up to that paper, from the perspective of researchers involved in building this summary of the tree of life: Is there a tree of life and should we reconstruct it? Is available data sufficient to reconstruct the tree of life? Do we have access to phylogenetic inferences in usable form? Can we combine different phylogenetic estimates across the tree of life? And finally, what is the future of understanding the tree of life? Read More

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