85,122 results match your criteria Eukaryotic Cell[Journal]


Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway.

Cell Physiol Biochem 2018 Dec 6;51(5):2136-2147. Epub 2018 Dec 6.

Background/aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC).

Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. Read More

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December 2018
2 Reads

Patatin-like lipolytic acyl hydrolases and galactolipid metabolism in marine diatoms of the genus Pseudo-nitzschia.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Dec 3. Epub 2018 Dec 3.

CNR-Istituto di Chimica Biomolecolare, Via Campi Flegrei 34, 80078, Pozzuoli, Naples, Italy. Electronic address:

Diatoms are eukaryotic microalgae that play a pivotal role in biological and geochemical marine cycles. These microorganisms are at the basis of the trophic chain and their lipids are essential components (e.g. Read More

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December 2018

Structural insight into substrate and product binding in an archaeal mevalonate kinase.

PLoS One 2018 6;13(12):e0208419. Epub 2018 Dec 6.

Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA, United States of America.

Mevalonate kinase (MK) is a key enzyme of the mevalonate pathway, which produces the biosynthetic precursors for steroids, including cholesterol, and isoprenoids, the largest class of natural products. Currently available crystal structures of MK from different organisms depict the enzyme in its unbound, substrate-bound, and inhibitor-bound forms; however, until now no structure has yet been determined of MK bound to its product, 5-phosphomevalonate. Here, we present crystal structures of mevalonate-bound and 5-phosphomevalonate-bound MK from Methanosarcina mazei (MmMK), a methanogenic archaeon. Read More

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December 2018
1 Read

A gradient-based, GPU-accelerated, high-precision contour-segmentation algorithm with application to cell membrane fluctuation spectroscopy.

PLoS One 2018 6;13(12):e0207376. Epub 2018 Dec 6.

Mechanics of Biological Membranes and Biorheology, Dpto. Química Física I, Universidad Complutense, Madrid, Spain.

We present a novel intensity-gradient based algorithm specifically designed for nanometer-segmentation of cell membrane contours obtained with high-resolution optical microscopy combined with high-velocity digital imaging. The algorithm relies on the image oversampling performance and computational power of graphical processing units (GPUs). Both, synthetic and experimental data are used to quantify the sub-pixel precision of the algorithm, whose analytic performance results comparatively higher than in previous methods. Read More

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December 2018

Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study.

PLoS Comput Biol 2018 Dec 6;14(12):e1006642. Epub 2018 Dec 6.

Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany.

The RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21. Read More

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December 2018
1 Read

Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10.

FEBS J 2018 Dec 6. Epub 2018 Dec 6.

Department of Physics, Indian Institute of Science, Bengaluru, 560012, India.

Abrin, an extremely cytotoxic Type-II ribosome inactivating protein (RIP), is a potential bio-warfare agent. Abrin A-chain (ABA) depurinates an adenosine of sarcin-ricin loop (SRL) from eukaryotic 28S rRNA thereby arresting protein synthesis and leading to cell death. Monoclonal antibody (mAb) D6F10 is the only known antibody that neutralizes ABA's activity in cell-free systems as well as abrin's toxicity in vitro and in vivo. Read More

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December 2018

Histones Predate the Split Between Bacteria and Archaea.

Bioinformatics 2018 Dec 6. Epub 2018 Dec 6.

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.

Motivation: Histones form octameric complexes called nucleosomes, which organize the genomic DNA of eukaryotes into chromatin. Each nucleosome comprises two copies each of the histones H2A, H2B, H3, and H4, which share a common ancestry. Although histones were initially thought to be a eukaryotic innovation, the subsequent identification of archaeal homologs led to the notion that histones emerged before the divergence of archaea and eukaryotes. Read More

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December 2018
3 Reads

M918: A novel cell penetrating peptide for effective delivery of HIV-1 Nef and Hsp20-Nef proteins into eukaryotic cell lines.

Curr HIV Res 2018 Dec 5. Epub 2018 Dec 5.

Pilot Nano-Biotechnology Department, Pasteur Institute of Iran, Tehran. Iran.

Background: HIV-1 Nef protein is a possible attractive target in development of therapeutic HIV vaccines including protein-based vaccines. The most important disadvantage of protein-based vaccines is their low immunogenicity which can be improved by heat shock proteins (Hsps) as an immunomodulator, and cell penetrating peptides (CPPs) as a carrier.

Methods: In this study, the HIV-1 Nef and Hsp20-Nef proteins were generated in E. Read More

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December 2018
3 Reads

Insulin action on protein synthesis and its association with eIF5A expression and hypusination.

Mol Biol Rep 2018 Dec 5. Epub 2018 Dec 5.

Laboratory of Biotechnology, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.

The hormone insulin plays a central role in the metabolism of carbohydrates, lipids, and proteins. In relation to protein metabolism, insulin stimulates amino acid uptake and activates protein synthesis in responsive cells by modulation of signal transduction pathways, such as associated to Akt/PkB, mTOR, S6Ks, 4E-BP1, and several translation initiation/elongation factors. In this context, there is no information on direct cellular treatment with insulin and effects on eukaryotic translation initiation factor 5A (eIF5A) regulation. Read More

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December 2018
1 Read

A carnivorous plant genetic map: pitcher/insect-capture QTL on a genetic linkage map of .

Life Sci Alliance 2018 Dec 29;1(6):e201800146. Epub 2018 Nov 29.

Department of Plant Biology, Miller Plant Sciences Building, University of Georgia, Athens, GA, USA.

The study of carnivorous plants can afford insight into their unique evolutionary adaptations and their interactions with prokaryotic and eukaryotic species. For (pitcher plants), we identified 64 quantitative trait loci (QTL) for insect-capture traits of the pitchers, providing the genetic basis for differences between the pitfall and lobster-trap strategies of insect capture. The linkage map developed here is based upon the F2 of a cross between and ; we mapped 437 single nucleotide polymorphism and simple sequence repeat markers. Read More

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December 2018
1 Read

Eukaryotic Voltage-Gated Sodium Channels: On Their Origins, Asymmetries, Losses, Diversification and Adaptations.

Front Physiol 2018 21;9:1406. Epub 2018 Nov 21.

Department of Biology, University of Waterloo, Waterloo, ON, Canada.

The appearance of voltage-gated, sodium-selective channels with rapid gating kinetics was a limiting factor in the evolution of nervous systems. Two rounds of domain duplications generated a common 24 transmembrane segment (4 × 6 TM) template that is shared amongst voltage-gated sodium (Na1 and Na2) and calcium channels (Ca1, Ca2, and Ca3) and leak channel (NALCN) plus homologs from yeast, different single-cell protists (heterokont and unikont) and algae (green and brown). A shared architecture in 4 × 6 TM channels include an asymmetrical arrangement of extended extracellular L5/L6 turrets containing a 4-0-2-2 pattern of cysteines, glycosylated residues, a universally short III-IV cytoplasmic linker and often a recognizable, C-terminal PDZ binding motif. Read More

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November 2018

Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay.

Nat Struct Mol Biol 2018 Dec 5. Epub 2018 Dec 5.

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.

5'-3' RNA decay pathways are critical for quality control and regulation of gene expression. Structural and biochemical studies have provided insights into the key nucleases that carry out deadenylation, decapping, and exonucleolysis during 5'-3' decay, but detailed understanding of how these activities are coordinated is only beginning to emerge. Here we review recent mechanistic insights into the control of 5'-3' RNA decay, including coupling between translation and decay, coordination between the complexes and activities that process 5' and 3' RNA termini, conformational control of enzymatic activity, liquid phase separation, and RNA modifications. Read More

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December 2018

Daily changes in phytoplankton lipidomes reveal mechanisms of energy storage in the open ocean.

Nat Commun 2018 Dec 5;9(1):5179. Epub 2018 Dec 5.

Department of Marine Chemistry and Geochemistry, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543, USA.

Sunlight is the dominant control on phytoplankton biosynthetic activity, and darkness deprives them of their primary external energy source. Changes in the biochemical composition of phytoplankton communities over diel light cycles and attendant consequences for carbon and energy flux in environments remain poorly elucidated. Here we use lipidomic data from the North Pacific subtropical gyre to show that biosynthesis of energy-rich triacylglycerols (TAGs) by eukaryotic nanophytoplankton during the day and their subsequent consumption at night drives a large and previously uncharacterized daily carbon cycle. Read More

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December 2018

The Noncoding RNA nc886 Regulates PKR Signaling and Cytokine Production in Human Cells.

J Immunol 2018 Dec 5. Epub 2018 Dec 5.

Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, 21428 Malmö, Sweden

Protein kinase RNA-activated (PKR) is a cytoplasmic receptor for dsRNA, and as such is involved in detection of viral infection. On binding dsRNA, PKR dimerizes, autophosphorylates, and then phosphorylates its substrate, eukaryotic translation initiation factor 2 subunit α (eIF2α), causing inhibition of mRNA translation and shutdown of viral protein production. However, active PKR has also been found to be involved in the NF-κB signaling pathway by inducing phosphorylation of IκBα. Read More

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December 2018

Rock substrate rather than black stain alterations drives microbial community structure in the passage of Lascaux Cave.

Microbiome 2018 Dec 5;6(1):216. Epub 2018 Dec 5.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS, INRA, VetAgro Sup, UMR5557/1418 Ecologie Microbienne, 69622, Villeurbanne, France.

Background: The World-famous UNESCO heritage from the Paleolithic human society, Lascaux Cave (France), has endeavored intense microclimatic perturbations, in part due to high touristic pressure. These perturbations have resulted in numerous disturbances of the cave ecosystem, including on its microbial compartment, which resulted in the formation of black stains especially on the rock faces of the passage. We investigated the cave microbiome in this part of Lascaux by sampling three mineral substrates (soil, banks, and inclined planes) on and outside stains to assess current cave microbial assemblage and explore the possibility that pigmented microorganisms involved in stain development occur as microbial consortia. Read More

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December 2018

mRNA-Mediated Duplexes Play Dual Roles in the Regulation of Bidirectional Ribosomal Frameshifting.

Int J Mol Sci 2018 Dec 4;19(12). Epub 2018 Dec 4.

Institute of Biochemistry, National Chung-Hsing University, 145 Xingda Road, Taichung 402, Taiwan.

In contrast to -1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates -1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical -1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro. Read More

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December 2018

Both Intrinsically Disordered Regions and Structural Domains Evolve Rapidly in Immune-Related Mammalian Proteins.

Int J Mol Sci 2018 Dec 4;19(12). Epub 2018 Dec 4.

Department of Life Science and Informatics, Maebashi Institute of Technology, 460-1 Kamisadori-machi, Maebashi-shi 371-0816, Japan.

Eukaryotic proteins consist of structural domains (SDs) and intrinsically disordered regions (IDRs), i.e., regions that by themselves do not assume unique three-dimensional structures. Read More

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December 2018

Development of an RNA expression platform controlled by viral internal ribosome entry sites.

J Microbiol Biotechnol 2018 Nov 28. Epub 2018 Nov 28.

Department of Biotechnology, The Catholic University of Korea, Bucheon, Korea.

Since 1990, many nucleic acid expression platforms consisting of DNA or RNA have been developed. However, RNA expression platforms have been neglected. Several such platforms capped at the 5' end of RNA by an anti-reverse cap analog have now been developed. Read More

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November 2018

Assessing Cellular Stress and Inflammation in Discrete Oxytocin-secreting Brain Nuclei in the Neonatal Rat Before and After First Colostrum Feeding.

J Vis Exp 2018 Nov 14(141). Epub 2018 Nov 14.

Department of Psychiatry, Columbia University; Department of Pathology & Cell Biology, Columbia University Medical Center;

The goal of this protocol is to isolate oxytocin-receptor rich brain nuclei in the neonatal brain before and after first colostrum feeding. The expression of proteins known to respond to metabolic stress was measured in brain-nuclei isolates using Western blotting. This was done to assess whether metabolic stress-induced nutrient insufficiency in the body triggered neuronal stress. Read More

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November 2018

The Galleria mellonella Waxworm Infection Model for Disseminated Candidiasis.

J Vis Exp 2018 Nov 17(141). Epub 2018 Nov 17.

Department of Microbiology, The Ohio State University; Department of Microbial Infection and Immunity, The Ohio State University;

Candida species are common fungal commensals of humans colonizing the skin, mucosal surfaces, and gastrointestinal tract. Under certain conditions, Candida can overgrow their natural niches resulting in debilitating mucosal infections as well as life-threatening systemic infections, which are a major focus of investigation due to their associated high mortality rates. Animal models of disseminated infection exist for studying disease progression and dissecting the characteristics of Candida pathogenicity. Read More

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November 2018

Bacterial sepsis triggers an antiviral response that causes translation shutdown.

J Clin Invest 2018 Dec 3. Epub 2018 Dec 3.

Department of Medicine.

In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses, as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. Read More

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December 2018

Targeting protein translation to prevent septic kidney injury.

Authors:
Sarah C Huen

J Clin Invest 2018 Dec 3. Epub 2018 Dec 3.

The development of acute kidney injury (AKI) in patients with sepsis causes significant morbidity and mortality. The pathogenesis of AKI in sepsis is incompletely understood. In this issue of the JCI, Hato et al. Read More

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December 2018

The role of plasminogen activators in stroke treatment: fibrinolysis and beyond.

Lancet Neurol 2018 Dec 13;17(12):1121-1132. Epub 2018 Nov 13.

Normandie Université, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders, Cyceron, Caen, France. Electronic address:

Although recent technical advances in thrombectomy have revolutionised acute stroke treatment, prevalence of disability and death related to stroke remain high. Therefore, plasminogen activators-eukaryotic, bacterial, or engineered forms that can promote fibrinolysis by converting plasminogen into active plasmin and facilitate clot breakdown-are still commonly used in the acute treatment of ischaemic stroke. Hence, plasminogen activators have become a crucial area for clinical investigation for their ability to recanalise occluded arteries in ischaemic stroke and to accelerate haematoma clearance in haemorrhagic stroke. Read More

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December 2018
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An additional role for chloroplast proteins-an amino acid reservoir for energy production during sugar starvation.

Plant Signal Behav 2018 Dec 3:1-4. Epub 2018 Dec 3.

d Department of Applied Plant Science, Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.

Autophagy is an evolutionarily conserved system that degrades intracellular components including proteins and organelles, and is important in the adaptive response to starvation in various eukaryotic organisms. Plant chloroplasts convert light energy into chemical energy and assimilate atmospheric carbon dioxide (CO) for carbohydrate production through photosynthesis reactions. We previously described an autophagy process for chloroplast degradation, during which a portion of chloroplasts are mobilized into the vacuole via autophagic vesicles termed Rubisco-containing bodies. Read More

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December 2018

Human RNF113A participates of pre-mRNA splicing in vitro.

J Cell Biochem 2018 Dec 2. Epub 2018 Dec 2.

Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Pre-messenger RNA (mRNA) splicing is an essential step in the control of eukaryotic gene expression. During splicing, the introns are removed from the gene transcripts as the exons are ligated to create mature mRNA sequences. Splicing is performed by the spliceosome, which is a macromolecular complex composed of five small nuclear RNAs (snRNAs) and more than 100 proteins. Read More

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December 2018

Photoactivated Colibactin Probes Induce Cellular DNA Damage.

Angew Chem Int Ed Engl 2018 Dec 3. Epub 2018 Dec 3.

Umeå University, Institute of Chemistry, Linneaus väg 6, 90187, Umeå, SWEDEN.

Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks+ bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form. Read More

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December 2018
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The enigmatic loss of light-independent chlorophyll biosynthesis from an Antarctic green alga in a light-limited environment.

New Phytol 2018 Dec 3. Epub 2018 Dec 3.

Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7, Canada.

Chlorophyll production is a complicated, multifaceted process. Indeed, the cyanobacterial progenitor of chloroplasts bestowed eukaryotic plants and algae with two distinct nonhomologous enzymes for reducing protochlorophyllide to chlorophyllide (the penultimate step of chlorophyll a biosynthesis): light-dependent (LPOR) and light-independent protochlorophyllide oxidoreductase (DPOR) (Armstrong, 1998; Fujita & Bauer, 2003; Reinbothe et al., 2010). Read More

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December 2018

Acetylation is the most abundant actin modification in Entamoeba histolytica, and modifications of actin's amino-terminal domain change cytoskeleton activities.

Cell Microbiol 2018 Dec 2:e12983. Epub 2018 Dec 2.

Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, Paris, France.

Actin is one of the most conserved, abundant and ubiquitous proteins in all eukaryotes characterized to date. Post-translation modifications of actin modify the organization of the actin-rich cytoskeleton. In particular, chemical modifications of actin's amino-terminal region determine how filamentous actin is organized into scaffolds. Read More

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December 2018

Crystal structure of Kumaglobin: a hexacoordinated heme protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus.

FEBS J 2018 Dec 1. Epub 2018 Dec 1.

Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Tardigrades, also known as water bears, can survive extreme conditions. For example, tardigrades have high tolerance to extreme desiccation because they can enter an anhydrobiotic state, in which they show no or nearly undetectable metabolic processes. Proteins from anhydrobiotic tardigrades with low homology to known proteins from other organisms are new potential targets for structural genomics. Read More

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December 2018

Targeting of tail-anchored proteins to Trichomonas vaginalis hydrogenosomes.

Mol Microbiol 2018 Dec 1. Epub 2018 Dec 1.

Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Průmyslová 595, 25242, Vestec, Czech Republic.

Tail-anchored (TA) proteins are membrane proteins that are found in all domains of life. They consist of an N-terminal domain that performs various functions and a single transmembrane domain (TMD) near the C-terminus. In eukaryotes, TA proteins are targeted to the membranes of mitochondria, the endoplasmic reticulum (ER), peroxisomes and in plants, chloroplasts. Read More

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December 2018

A Method for SUMO Modification of Proteins .

Bio Protoc 2018 Oct;8(19)

Department of Biochemistry & Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

The Small Ubiquitin-related Modifier (SUMO) is a protein that is post-translationally added to and reversibly removed from other proteins in eukaryotic cells. SUMO and enzymes of the SUMO pathway are well conserved from yeast to humans and SUMO modification regulates a variety of essential cellular processes including transcription, chromatin remodeling, DNA damage repair, and cell cycle progression. One of the challenges in studying SUMO modification is the relatively low steady-state level of a SUMO-modified protein due in part to the activity of SUMO deconjugating enzymes known as SUMO Isopeptidases or SENPs. Read More

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October 2018
1 Read

Detecting intracellular thiol redox state in leukaemia and heterogeneous immune cell populations: An optimised protocol for digital flow cytometers.

MethodsX 2018 1;5:1473-1483. Epub 2018 Nov 1.

School of Science and the Environment, University of Worcester, Worcester, UK.

Flow cytometric methods for detecting and quantifying intracellular thiol content using fluorescein-5-maleimide (F5M) in viable eukaryotic cells date back to 1983 (Durand and Olive [1]). There has been little development in these methodologies since that time, a period that has witnessed huge technological advances, particularly with the emergence of digital multi-parameter flow cytometric systems. Concurrent advancement in our understanding of redox regulation within eukaryotic cellular systems has also followed, whereby it is now accepted that cysteine thiols partake in redox reactions, which regulate protein activity and function (Groitl and Jakob (2014), Won et al. Read More

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November 2018

The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity.

Authors:
Darja Kanduc

Biol Chem 2018 Dec 3. Epub 2018 Dec 3.

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, I-70124 Bari, Italy.

Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Read More

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December 2018
1 Read

Alternative biosynthetic starter units enhance the structural diversity of cyanobacterial lipopeptides.

Appl Environ Microbiol 2018 Nov 30. Epub 2018 Nov 30.

The Czech Academy of Sciences, Institute of Microbiology, Center Algatech, Třeboň, Czech Republic

Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although biosynthetic gene clusters for several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Read More

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November 2018
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The Genetic Landscape of Diamond-Blackfan Anemia.

Am J Hum Genet 2018 Nov 21. Epub 2018 Nov 21.

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole-exome sequencing (WES). We identified relevant rare and predicted damaging mutations for 78% of individuals. Read More

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November 2018

Tales of Detailed Poly(A) Tails.

Trends Cell Biol 2018 Nov 29. Epub 2018 Nov 29.

Division of Biology, University of California, San Diego (USCD), La Jolla, CA 92093-0349, USA. Electronic address:

Poly(A) tails are non-templated additions of adenosines at the 3' ends of most eukaryotic mRNAs. In the nucleus, these RNAs are co-transcriptionally cleaved at a poly(A) site and then polyadenylated before being exported to the cytoplasm. In the cytoplasm, poly(A) tails play pivotal roles in the translation and stability of the mRNA. Read More

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November 2018

CLIP-Seq in Bacteria: Global Recognition Patterns of Bacterial RNA-Binding Proteins.

Methods Enzymol 2018 22;612:127-145. Epub 2018 Sep 22.

Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. Electronic address:

RNA-protein interactions are at the heart of many central cellular processes, and RNA-binding proteins (RBPs) associate with virtually all RNA molecules in a cell. In bacteria, global RBPs, often in conjunction with small regulatory RNAs, affect physiology and virulence by controlling transcription, translation, and RNA decay. To understand how these regulatory proteins orchestrate global gene expression, detailed maps of their cellular RNA binding sites are required. Read More

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September 2018

The Challenges of Genome-Wide Studies in a Unicellular Eukaryote With Two Nuclear Genomes.

Methods Enzymol 2018 31;612:101-126. Epub 2018 Aug 31.

Institute for Integrative Biology of the Cell (I2BC), CNRS, CEA, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette CEDEX, France.

We present here methods to study a eukaryotic microorganism with two nuclear genomes, both originating from the same zygotic genome. Paramecium, like other ciliates, is characterized by nuclear dimorphism, which is the presence of two types of nuclei with distinct organization and functions in the same cytoplasm. The two diploid germline micronuclei (MIC) undergo meiosis and fertilization to transmit the genetic information across sexual generations. Read More

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The Hsp70-Hsp90 Chaperone Cascade in Protein Folding.

Trends Cell Biol 2018 Nov 28. Epub 2018 Nov 28.

Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; Science for Life, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address:

Conserved families of molecular chaperones assist protein folding in the cell. Here we review the conceptual advances on three major folding routes: (i) spontaneous, chaperone-independent folding; (ii) folding assisted by repetitive Hsp70 cycles; and (iii) folding by the Hsp70-Hsp90 cascades. These chaperones prepare their protein clients for folding on their own, without altering their folding path. Read More

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November 2018

Low-dose stimulation of growth of the harmful alga, Prymnesium parvum, by glyphosate and glyphosate-based herbicides.

Harmful Algae 2018 Dec 17;80:130-139. Epub 2018 Nov 17.

U.S. Geological Survey, Texas Cooperative Fish and Wildlife Research Unit and Departments of Natural Resources Management and Biological Sciences, Texas Tech University, Lubbock, TX, 79409-2120, USA. Electronic address:

Glyphosate-based herbicides (GBH) are widely used around the globe. While generally toxic to phototrophs, organic phosphorus in glyphosate can become available to glyphosate-resistant phytoplankton and contribute to algal bloom development. Few studies have examined the effects of GBH on growth of eukaryotic microalgae and information for the toxic bloom-forming haptophyte, Prymnesium parvum, is limited. Read More

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December 2018

AMPK: Regulation of Metabolic Dynamics in the Context of Autophagy.

Int J Mol Sci 2018 Nov 29;19(12). Epub 2018 Nov 29.

Instituto de Investigación Sanitaria del Principado de Asturias, 33011 Oviedo, Spain.

Eukaryotic cells have developed mechanisms that allow them to link growth and proliferation to the availability of energy and biomolecules. AMPK (adenosine monophosphate-activated protein kinase) is one of the most important molecular energy sensors in eukaryotic cells. AMPK activity is able to control a wide variety of metabolic processes connecting cellular metabolism with energy availability. Read More

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November 2018

The inhibition of checkpoint activation by telomeres does not involve exclusion of dimethylation of histone H4 lysine 20 (H4K20me2).

F1000Res 2018 9;7:1027. Epub 2018 Jul 9.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.

DNA double-strand breaks (DSBs) activate the DNA damage checkpoint machinery to pause or halt the cell cycle.  Telomeres, the specific DNA-protein complexes at linear eukaryotic chromosome ends, are capped DSBs that do not activate DNA damage checkpoints.  This "checkpoint privileged" status of telomeres was previously investigated in the yeast  lacking the major double-stranded telomere DNA binding protein Taz1. Read More

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tRNA Translocation by the Eukaryotic 80S Ribosome and the Impact of GTP Hydrolysis.

Cell Rep 2018 Dec;25(10):2676-2688.e7

Institut für Medizinische Physik und Biophysik, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address:

Translocation moves the tRNA⋅mRNA module directionally through the ribosome during the elongation phase of protein synthesis. Although translocation is known to entail large conformational changes within both the ribosome and tRNA substrates, the orchestrated events that ensure the speed and fidelity of this critical aspect of the protein synthesis mechanism have not been fully elucidated. Here, we present three high-resolution structures of intermediates of translocation on the mammalian ribosome where, in contrast to bacteria, ribosomal complexes containing the translocase eEF2 and the complete tRNA⋅mRNA module are trapped by the non-hydrolyzable GTP analog GMPPNP. Read More

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December 2018

Allele-specific genome editing using CRISPR-Cas9 is associated with loss of heterozygosity in diploid yeast.

Nucleic Acids Res 2018 Dec 5. Epub 2018 Dec 5.

Department of Biotechnology, Delft University of Technology, Delft 2629HZ, The Netherlands.

Targeted DNA double-strand breaks (DSBs) with CRISPR-Cas9 have revolutionized genetic modification by enabling efficient genome editing in a broad range of eukaryotic systems. Accurate gene editing is possible with near-perfect efficiency in haploid or (predominantly) homozygous genomes. However, genomes exhibiting polyploidy and/or high degrees of heterozygosity are less amenable to genetic modification. Read More

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December 2018

Homologous pairing activities of Arabidopsis thaliana RAD51 and DMC1.

J Biochem 2018 Dec 5. Epub 2018 Dec 5.

Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.

In eukaryotes, homologous recombination plays a pivotal role in both genome maintenance and generation of genetic diversity. Eukaryotic RecA homologues, RAD51 and DMC1, are key proteins in homologous recombination that promote pairing between homologous DNA sequences. Arabidopsis thaliana is a prominent model plant for studying eukaryotic homologous recombination. Read More

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December 2018

Stress-inducible NHEJ in bacteria: function in DNA repair and acquisition of heterologous DNA.

Nucleic Acids Res 2018 Dec 4. Epub 2018 Dec 4.

LIPM, Université de Toulouse, INRA, CNRS, Castanet-Tolosan, France.

DNA double-strand breaks (DSB) in bacteria can be repaired by non-homologous end-joining (NHEJ), a two-component system relying on Ku and LigD. While performing a genetic characterization of NHEJ in Sinorhizobium meliloti, a representative of bacterial species encoding several Ku and LigD orthologues, we found that at least two distinct functional NHEJ repair pathways co-exist: one is dependent on Ku2 and LigD2, while the other depends on Ku3, Ku4 and LigD4. Whereas Ku2 likely acts as canonical bacterial Ku homodimers, genetic evidences suggest that Ku3-Ku4 form eukaryotic-like heterodimers. Read More

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December 2018
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MEHMO syndrome mutation EIF2S3-I259M impairs initiator Met-tRNAiMet binding to eukaryotic translation initiation factor eIF2.

Nucleic Acids Res 2018 Dec 4. Epub 2018 Dec 4.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

The heterotrimeric eukaryotic translation initiation factor (eIF) 2 plays critical roles in delivering initiator Met-tRNAiMet to the 40S ribosomal subunit and in selecting the translation initiation site. Genetic analyses of patients with MEHMO syndrome, an X-linked intellectual disability syndrome, have identified several unique mutations in the EIF2S3 gene that encodes the γ subunit of eIF2. To gain insights into the molecular consequences of MEHMO syndrome mutations on eIF2 function, we generated a yeast model of the human eIF2γ-I259M mutant, previously identified in a patient with MEHMO syndrome. Read More

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December 2018

Single-nucleotide-resolution mapping of DNA gyrase cleavage sites across the Escherichia coli genome.

Nucleic Acids Res 2018 Dec 4. Epub 2018 Dec 4.

Centre for Life Sciences, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia.

An important antibiotic target, DNA gyrase is an essential bacterial enzyme that introduces negative supercoils into DNA and relaxes positive supercoils accumulating in front of moving DNA and RNA polymerases. By altering the superhelical density, gyrase may regulate expression of bacterial genes. The information about how gyrase is distributed along genomic DNA and whether its distribution is affected by drugs is scarce. Read More

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December 2018
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Spliceosome factors target timeless () mRNA to control clock protein accumulation and circadian behavior in Drosophila.

Elife 2018 Dec 5;7. Epub 2018 Dec 5.

Chronobiology Program at Penn, Howard Hughes Medical Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States.

Transcription-translation feedback loops that comprise eukaryotic circadian clocks rely upon temporal delays that separate the phase of active transcription of clock genes, such as Drosophila and from negative feedback by the two proteins. However, our understanding of the mechanisms involved is incomplete. Through an RNA interference screen, we found that pre-mRNA processing 4 (PRP4) kinase, a component of the U4/U5. Read More

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December 2018

Multivalent thiosialosides and their synergistic interaction with pathogenic sialidases.

Chemistry 2018 Dec 5. Epub 2018 Dec 5.

University of Nantes, Department of Chemistry, 2 rue de la Houssinière, 44300, Nantes, FRANCE.

Sialidases (SA) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses and parasites. The catalytic domain of SA are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Here we designed non-hydrolyzable multivalent thiosialosides as probes and inhibitors of V. Read More

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December 2018