Bioessays 2017 Sep 15. Epub 2017 Sep 15.

School of Biotechnology & Biomolecular Sciences UNSW Sydney, NSW, Australia.

Bioessays 2017 Sep 13. Epub 2017 Sep 13.

Dr. T. C. Boothby, Prof. G. J. Pielak, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers (tiny animals) "coming back to life" upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. Read More

Bioessays 2017 Sep 13. Epub 2017 Sep 13.

Bioessays 2017 Sep 12. Epub 2017 Sep 12.

Department of Physics Universität zu Köln, Köln, Nordrhein-Westfalen, Germany.

Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Read More

Bioessays 2017 Sep 11. Epub 2017 Sep 11.

Clinic for Anesthesiology, Zagreb University Hospital Center, Zagreb, Croatia.

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. Read More

Bioessays 2017 Sep 11. Epub 2017 Sep 11.

Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.

How epithelial tissues are able to self-renew to maintain homeostasis and regenerate in response to injury remains a persistent question. The transcriptional effectors YAP and TAZ are increasingly being recognized as central mediators of epithelial stem cell biology, and a wealth of recent studies have been directed at understanding the control and activity of these factors. Recent work by Hu et al. Read More

Bioessays 2017 Sep 11. Epub 2017 Sep 11.

Department of Radiation Oncology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Read More

Bioessays 2017 Sep 8. Epub 2017 Sep 8.

Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, Site Jacques Monod, Lyon, France.

The biogenesis of RNAs and proteins is a threat to the cell. Indeed, the act of transcription and nascent RNAs challenge DNA stability. Both RNAs and nascent proteins can also initiate the formation of toxic aggregates because of their physicochemical properties. Read More

Bioessays 2017 Sep 8. Epub 2017 Sep 8.

School of Systems Biology, George Mason University, Fairfax, VA, USA.

Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria. Read More

Bioessays 2017 Sep 7. Epub 2017 Sep 7.

MRC Human Genetic Unit, MRC IGMM, University of Edinburgh, Edinburgh, UK.

Bioessays 2017 Sep 1. Epub 2017 Sep 1.

Department of Biology, Indiana University, Bloomington, IN, USA.

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. Read More

Bioessays 2017 Sep 1. Epub 2017 Sep 1.

Institute of Cell and Developmental Biology, Department of Biology, University of Fribourg, Fribourg, Switzerland.

The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non-bilaterian metazoans, both with and without neurons and their closest relatives already contain many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non-bilaterian metazoans. Read More

Bioessays 2017 Sep;39(9)

The University of Western Ontario - Oncology, Ontario, Canada.

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and 'acausal' recognition of some marker or signature. Read More

Bioessays 2017 Sep;39(9)

Bioessays 2017 Aug 22. Epub 2017 Aug 22.

Institute of Health and Environmental Research, Cleveland, OH, USA.

Bioessays 2017 Aug 17. Epub 2017 Aug 17.

Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie de la Méditerranée (IMM), Aix-Marseille Université - CNRS, Marseille, France.

The Type VI secretion system (T6SS) is a multiprotein and mosaic apparatus that delivers protein effectors into prokaryotic or eukaryotic cells. Recent data on the enteroaggregative Escherichia coli (EAEC) T6SS have provided evidence that the TssA protein is a key component during T6SS biogenesis. The T6SS comprises a trans-envelope complex that docks the baseplate, a cytoplasmic complex that represents the assembly platform for the tail. Read More

Bioessays 2017 Aug 9. Epub 2017 Aug 9.

Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture (3C)-based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Read More

Bioessays 2017 Sep 9;39(9). Epub 2017 Aug 9.

Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. Read More

Bioessays 2017 Aug 8. Epub 2017 Aug 8.

Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.

Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and rapidly transported into the organelle by a complex machinery. The data gathered in recent years suggest that this machinery operates through a syringe-like mechanism, in which the shuttling receptor PEX5 - the "plunger" - pushes a newly synthesized protein all the way through a peroxisomal transmembrane protein complex - the "barrel" - into the matrix of the organelle. Notably, insertion of cargo-loaded receptor into the "barrel" is an ATP-independent process, whereas extraction of the receptor back into the cytosol requires its monoubiquitination and the action of ATP-dependent mechanoenzymes. Read More

Bioessays 2017 Sep 8;39(9). Epub 2017 Aug 8.

Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Here we review concepts related to an ensemble description of G-protein-coupled receptors (GPCRs). The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor (A2A R), a prototypical class A GPCR. Read More

Bioessays 2017 Sep 8;39(9). Epub 2017 Aug 8.

Department of Periodontics, University of Washington, Seattle, WA, USA.

After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the "twilight of death" - the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. Read More

Bioessays 2017 Sep 7;39(9). Epub 2017 Aug 7.

Medical Biochemistry, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.

Recently, the group of McBride reported a stunning observation regarding peroxisome biogenesis: newly born peroxisomes are hybrids of mitochondrial and ER-derived pre-peroxisomes. What was stunning? Studies performed with the yeast Saccharomyces cerevisiae had convincingly shown that peroxisomes are ER-derived, without indications for mitochondrial involvement. However, the recent finding using fibroblasts dovetails nicely with a mechanism inferred to be driving the eukaryotic invention of peroxisomes: reduction of mitochondrial reactive oxygen species (ROS) generation associated with fatty acid (FA) oxidation. Read More

Bioessays 2017 Sep 28;39(9). Epub 2017 Jul 28.

Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.

The maintenance of cell size homeostasis has been studied for years in different cellular systems. With the focus on 'what regulates cell size', the question 'why cell size needs to be maintained' has been largely overlooked. Recent evidence indicates that animal cells exhibit nonlinear cell size dependent growth rates and mitochondrial metabolism, which are maximal in intermediate sized cells within each cell population. Read More

Bioessays 2017 Sep 28;39(9). Epub 2017 Jul 28.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.

Galectin-3 and LTB4 are pro-inflammatory molecules recently shown to directly cause insulin resistance in mouse and human cells. They are highly expressed in the obese state, and can be targeted both genetically and pharmacologically to improve insulin sensitivity in vivo. This expands on previous research showing that targeting inflammatory cytokines can be insulin sensitizing in animal models. Read More

Bioessays 2017 Aug;39(8)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Phototoxicity frequently occurs during live fluorescence microscopy, and its consequences are often underestimated. Damage to cellular macromolecules upon excitation light illumination can impair sample physiology, and even lead to sample death. In this review, we explain how phototoxicity influences live samples, and we highlight that, besides the obvious effects of phototoxicity, there are often subtler consequences of illumination that are imperceptible when only the morphology of samples is examined. Read More

Bioessays 2017 Aug;39(8)

Bioessays 2017 Aug;39(8)

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.

Biochemical and cryo-electron microscopy studies have just been published revealing interactions among proteins of the yeast replisome that are important for highly coordinated synthesis of the two DNA strands of the nuclear genome. These studies reveal key interactions important for arranging DNA polymerases α, δ, and ϵ for leading and lagging strand replication. The CMG (Mcm2-7, Cdc45, GINS) helicase is central to this interaction network. Read More

Bioessays 2017 Sep 21;39(9). Epub 2017 Jul 21.

Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.

Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE). Read More

Bioessays 2017 Sep 18;39(9). Epub 2017 Jul 18.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

The mammalian Zc3h12a/MCPIP1/Regnase-1, an extensively studied regulator of inflammatory response, is the founding member of a ribonuclease family, which includes proteins related by the presence of the so-called Zc3h12a-like NYN domain. Recently, several related proteins have been described in Caenorhabditis elegans, allowing comparative evaluation of molecular functions and biological roles of these ribonucleases. We discuss the structural features of these proteins, which endow some members with ribonuclease (RNase) activity while others with auxiliary or RNA-independent functions. Read More

Bioessays 2017 Sep 13;39(9). Epub 2017 Jul 13.

Department of Biology, Tufts University, Medford, MA, USA.

In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in maintaining functional repetitive regions of the genome such as telomeres and centromeres. Read More

Bioessays 2017 Aug 13;39(8). Epub 2017 Jul 13.

Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.

Could 10-20% of autism be prevented? We hypothesize that nonsyndromic or "essential" autism involves extreme male bias in infants who are genetically normal, but they develop deficiency of carnitine and perhaps other nutrients in the brain causing autism that may be amenable to early reversal and prevention. That brain carnitine deficiency might cause autism is suggested by reports of severe carnitine deficiency in autism and by evidence that TMLHE deficiency - a defect in carnitine biosynthesis - is a risk factor for autism. A gene on the X chromosome (SLC6A14) likely escapes random X-inactivation (a mixed epigenetic and genetic regulation) and could limit carnitine transport across the blood-brain barrier in boys compared to girls. Read More

Bioessays 2017 Aug 12;39(8). Epub 2017 Jul 12.

Department of Cell Biology, Duke University Medical School, Durham, NC 27710, USA.

An important question for bacterial cell division is how the invaginating septum can overcome the turgor force generated by the high osmolarity of the cytoplasm. I suggest that it may not need to. Several studies in Gram-negative bacteria have shown that the periplasm is isoosmolar with the cytoplasm. Read More

Bioessays 2017 Aug 12;39(8). Epub 2017 Jul 12.

Sylvius Laboratory, Institute of Biology, University of Leiden, Leiden, The Netherlands.

We show the vertebrate anterior -posterior axis is made by time space translation (TST). 1/ TST of Hox temporal to spatial collinearity makes the trunk part of the axis. 2/TST continues into the head. Read More

Bioessays 2017 Aug 10;39(8). Epub 2017 Jul 10.

Department of Oncology, University of Western Ontario, London, Ontario, Canada.

From an evolutionary perspective, both atavism and somatic evolution/convergent evolution theories can account for the consistent occurrence, and astounding attributes of cancers: being able to evolve from a single cell to a complex organized system, and malignant transformations showing significant similarities across organs, individuals, and species. Here, we first provide an overview of these two hypotheses, including the possibility of them not being mutually exclusive, but rather potentially representing the two extremes of a continuum in which the diversity of cancers can emerge. In reviewing the current literature, we also discuss the criteria that should be applied to discriminate between the two competing theories and to determine their relevant contributions to oncogenesis and cancer progression. Read More

Bioessays 2017 Aug 7;39(8). Epub 2017 Jul 7.

Centre for Dermatology Research, School of Biological Sciences, University of Manchester, Manchester, UK.

Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition. Read More

Bioessays 2017 Sep 6;39(9). Epub 2017 Jul 6.

Département de Biologie, Université de Sherbrooke, Sherbrooke, Québec, Canada.

Can mammalian mothers adaptively control the sex of their offspring? The influential Trivers-Willard hypothesis (TWH) proposes that when maternal condition increases the fitness of sons more than that of daughters, the proportion of sons produced should increase with maternal condition. Studies of mammals, however, often fail to support this hypothesis. This article highlights recent advances, including studies on the assumptions of the TWH and physiological mechanisms for sex-ratio manipulation. Read More

Bioessays 2017 Aug 4;39(8). Epub 2017 Jul 4.

Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

In this review, we summarize recent work exploring a novel conceptual approach termed "synthetic essentiality" as a means for targeting specific tumor suppressor gene deficiencies in cancer. With the aid of extensive publically available cancer genome and clinical databases, "synthetic essentiality" could be utilized to identify synthetic essential genes, which might be occasionally deleted in some cancers but almost always retained in the context of a specific tumor suppressor deficiency. Synthetic essentiality expands the existing concepts for therapeutic strategies, including oncogene addiction, tumor maintenance, synthetic, and collateral lethality, to provide a framework for the discovery of cancer-specific vulnerabilities. Read More

Bioessays 2017 Jul;39(7)

Bioessays 2017 Aug 16;39(8). Epub 2017 Jun 16.

Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.

The instability of microsatellite DNA repeats is responsible for at least 40 neurodegenerative diseases. Recently, Mirkin and co-workers presented a novel mechanism for microsatellite expansions based on break-induced replication (BIR) at sites of microsatellite-induced replication stalling and fork collapse. The BIR model aims to explain single-step, large expansions of CAG/CTG trinucleotide repeats in dividing cells. Read More

Bioessays 2017 Aug 16;39(8). Epub 2017 Jun 16.

Faculty of Biology and Medicine, Center for Integrative Genomics, Génopode Building, University of Lausanne, Lausanne CH-1015, Switzerland.

Chemosensation and mechanosensation cover an enormous spectrum of processes by which animals use information from the environment to adapt their behavior. For pragmatic reasons, these sensory modalities are commonly investigated independently. Recent advances, however, have revealed numerous situations in which they function together to control animals' actions. Read More

Bioessays 2017 Aug 16;39(8). Epub 2017 Jun 16.

Laboratory for Cell Biology, Philipps University Marburg, Marburg, Germany.

Is the spatial organization of membranes and compartments within cells subjected to any rules? Cellular compartmentation differs between prokaryotic and eukaryotic life, because it is present to a high degree only in eukaryotes. In 1964, Prof. Eberhard Schnepf formulated the compartmentation rule (Schnepf theorem), which posits that a biological membrane, the main physical structure responsible for cellular compartmentation, usually separates a plasmatic form a non-plasmatic phase. Read More

Bioessays 2017 Aug 16;39(8). Epub 2017 Jun 16.

Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana, IL, USA.

The popular textbook image of viruses as noxious and selfish genetic parasites greatly underestimates the beneficial contributions of viruses to the biosphere. Given the crucial dependency of viruses to reproduce in an intracellular environment, viruses that engage in excessive killing (lysis) can drive their cellular hosts to extinction and will not survive. The lytic mode of virus propagation must, therefore, be tempered and balanced by non-lytic modes of virus latency and symbiosis. Read More

Bioessays 2017 Jul 14;39(7). Epub 2017 Jun 14.

European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Bioessays 2017 Jul 8;39(7). Epub 2017 Jun 8.

Department of Mathematics, Imperial College London, London, UK.

Heterogeneity in mitochondrial content has been previously suggested as a major contributor to cellular noise, with multiple studies indicating its direct involvement in biomedically important cellular phenomena. A recently published dataset explored the connection between mitochondrial functionality and cell physiology, where a non-linearity between mitochondrial functionality and cell size was found. Using mathematical models, we suggest that a combination of metabolic scaling and a simple model of cell death may account for these observations. Read More

Bioessays 2017 Jul 8;39(7). Epub 2017 Jun 8.

Research Group for Evolutionary Immunogenomics, Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Plön, Germany.

Bioessays 2017 Jul 7;39(7). Epub 2017 Jun 7.

Department of Biology, McGill University, Montreal, Quebec, Canada.

The segregation of homologous chromosomes in meiosis depends on their ability to locate one another in the nucleus and establish a physical association through crossing over. A tightly regulated number of crossovers (COs) emerges following repair of induced DNA double-strand breaks by homologous recombination (HR), but the process of how HR intermediates transition into COs is still poorly understood. Two recent studies by Ahuja et al. Read More

Bioessays 2017 Jul 7;39(7). Epub 2017 Jun 7.

Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, Principado de Asturias, Spain.

Interindividual variability is an inherent characteristic of biological systems. Whereas the underlying molecular sources of interindividual variability remain poorly understood, recent work by Ecker et al. (Ecker S, Chen L, Pancaldi V, Bagger FO, et al. Read More

Bioessays 2017 Jul 5;39(7). Epub 2017 Jun 5.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.

Recent analysis of genome sequences has identified individuals that are healthy despite carrying severe disease-associated mutations. A possible explanation is that these individuals carry a second genomic perturbation that can compensate for the detrimental effects of the disease allele, a phenomenon referred to as suppression. In model organisms, suppression interactions are generally divided into two classes: genomic suppressors which are secondary mutations in the genome that bypass a mutant phenotype, and dosage suppression interactions in which overexpression of a suppressor gene rescues a mutant phenotype. Read More

Bioessays 2017 Jul 5;39(7). Epub 2017 Jun 5.

Tel-Aviv University - History and Philosophy, Tel-Aviv, Israel.

There are four major hypotheses (H1, H2, H3, and H4) as to the source of missing heritability. We propose that estimates obtained from GWAS underestimate heritability by not taking into account non-DNA (epigenetic) sources of heritability. Taking those factors into account (H4) should result in increased heritability estimates. Read More

Bioessays 2017 Jul 5;39(7). Epub 2017 Jun 5.

Brain Institute, Universidade Federal do Rio Grande do Norte, Natal - RN, Brazil.

In this manuscript we describe Proteogenomics Viewer, a web-based tool that collects MS peptide identification, indexes to genomic sequence and structure, assigns exon usage, reports the identified protein isoforms with genomic alignments and, most importantly, allows the inspection of MS2 information for proper peptide identification. It also provides all performed indexing to facilitate global analysis of the data. The relevance of such tool is that there has been an increase in the number of proteogenomic efforts to improve the annotation of both genomics and proteomics data, culminating with the release of the two human proteome drafts. Read More