6,764,680 results match your criteria Protein Expression and Purification [Journal]

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Characterization of distinct mechanism of agonist-induced canine platelet activation.

J Vet Sci 2018 Dec 4. Epub 2018 Dec 4.

Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.

Platelet activation plays a major role in hemostasis and thrombosis. Various agonists including ADP and thrombin interact with GPCRs which transduce signals from the cell surface to intracellular effectors through various G proteins. Recent studies have elucidated the role of these receptors and their corresponding G proteins in the regulation of events involved in platelet activation. Read More

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December 2018

Genome-wide association study of degenerative mitral valve disease in Maltese dogs.

J Vet Sci 2018 Dec 4. Epub 2018 Dec 4.

Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, 05030, Korea.

Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Read More

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December 2018

Effect of an insect protein-based diet on clinical signs of dogs with cutaneous adverse food reactions.

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018 Oct 12;46(5):297-302. Epub 2018 Dec 12.

Objective: Edible insects (like mealworms, locusts and crickets) contain energy, protein, fatty acids, minerals and trace elements and have been found to be high quality food sources. They could provide a new food source for patients with adverse food reactions, as well as being of ecological and ethical interest. The aim of this study was to evaluate the effect of a new commercially available, insect protein-based diet on the clinical signs in those dogs via Canine Atopic Dermatitis Lesion Index (CADLI), Pruritus Visual Analogue Scale (PVAS) and coat quality score. Read More

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October 2018
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Factor cooperation for chromosome discrimination in Drosophila.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Molecular Biology Division, Biomedical Center, Faculty of Medicine and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität Munich, 82151 Martinsried, Germany.

Transcription regulators select their genomic binding sites from a large pool of similar, non-functional sequences. Although general principles that allow such discrimination are known, the complexity of DNA elements often precludes a prediction of functional sites. The process of dosage compensation in Drosophila allows exploring the rules underlying binding site selectivity. Read More

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December 2018

MAGE genes in the kidney: identification of MAGED2 as upregulated during kidney injury and in stressed tubular cells.

Nephrol Dial Transplant 2018 Dec 11. Epub 2018 Dec 11.

Nephrology, IIS-Fundacion Jimenez Diaz-Universidad Autonoma de Madrid and Fundacion Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.

Background: Mutations in Melanoma Antigen-encoding Gene D2 (MAGED2) promote tubular dysfunction, suggesting that MAGE proteins may play a role in kidney pathophysiology. We have characterized the expression and regulation of MAGE genes in normal kidneys and during kidney disease.

Methods: The expression of MAGE genes and their encoded proteins was explored by systems biology multi-omics (kidney transcriptomics and proteomics) in healthy adult murine kidneys and following induction of experimental acute kidney injury (AKI) by a folic acid overdose. Read More

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December 2018

Oocyte-Secreted Factors Synergize with FSH to Promote Aromatase Expression in Primary Human Cumulus Cells.

J Clin Endocrinol Metab 2018 Dec 11. Epub 2018 Dec 11.

Department of Physiology and Biophysics, University of Illinois at Chicago.

Context: The role of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) on aromatase regulation is poorly understood in humans.

Objective: Determine GDF9 and BMP15 effects on follicle-stimulating hormone (FSH) stimulation of estradiol production in primary human cumulus granulosa cells (GCs). We hypothesized that the combination of GDF9 and BMP15 potentiates FSH-induced aromatase expression. Read More

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December 2018

A coronary artery disease-associated tRNAThr mutation altered mitochondrial function, apoptosis and angiogenesis.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

The tissue specificity of mitochondrial tRNA mutations remains largely elusive. In this study, we demonstrated the deleterious effects of tRNAThr 15927G>A mutation that contributed to pathogenesis of coronary artery disease. The m. Read More

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December 2018

Intrinsically disordered regions regulate both catalytic and non-catalytic activities of the MutLα mismatch repair complex.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.

Intrinsically disordered regions (IDRs) are present in at least 30% of the eukaryotic proteome and are enriched in chromatin-associated proteins. Using a combination of genetics, biochemistry and single-molecule biophysics, we characterize how IDRs regulate the functions of the yeast MutLα (Mlh1-Pms1) mismatch repair (MMR) complex. Shortening or scrambling the IDRs in both subunits ablates MMR in vivo. Read More

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December 2018

Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.

Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. Read More

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December 2018

Educational level and risk of chronic kidney disease: longitudinal data from the PREVEND study.

Nephrol Dial Transplant 2018 Dec 12. Epub 2018 Dec 12.

Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: The longitudinal association between low education and chronic kidney disease (CKD) and its underlying mechanisms is poorly characterized. We therefore examined the association of low education with incident CKD and change in kidney function, and explored potential mediators of this association.

Methods: We analysed data on 6078 participants from the community-based Prevention of Renal and Vascular End-stage Disease study. Read More

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December 2018

Allosteric DNAzyme-based DNA logic circuit: operations and dynamic analysis.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Key Laboratory of Advanced Design and Intelligent Computing, Dalian University, Ministry of Education, Dalian 116622, China.

Recently, due to the dual roles of DNA and enzyme, DNAzyme has been widely used in the field of DNA circuit, which has a wide range of applications in bio-engineered system, information processing and biocomputing. In fact, the activity of DNAzymes was regulated by subunits assembly, pH control and metal ions triggers. However, those regulations required to change the sequences of whole DNAzyme, as separating parts and inserting extra DNA sequence. Read More

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December 2018

A 12-wk whole-grain wheat intervention protects against hepatic fat: the Graandioos study, a randomized trial in overweight subjects.

Am J Clin Nutr 2018 Dec;108(6):1264-1274

Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands.

Background: Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions.

Objective: The aim of this study was to investigate the potential benefits of WGW consumption compared with RW consumption on liver health and associated parameters. Read More

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December 2018

Structural insights into nucleotide and protein sequence of Ageritin: a novel prototype of fungal ribotoxin.

J Biochem 2018 Dec 12. Epub 2018 Dec 12.

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DISTABIF), University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, Caserta, Italy.

Here, we report the amino acid sequence of Ageritin, the first ribotoxin-like protein from basidiomycetes (Agrocybe aegerita). This protein consists of 135 amino acid residues with a theoretical molecular mass of 14801.80 Da (experimental mass 14802. Read More

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December 2018
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Archaeal NSUN6 catalyzes m5C72 modification on a wide-range of specific tRNAs.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P.R. China.

Human NOL1/NOP2/Sun RNA methyltransferase family member 6 (hNSun6) generates 5-methylcytosine (m5C) at C72 of four specific tRNAs, and its homologs are present only in higher eukaryotes and hyperthermophilic archaea. Archaeal NSun6 homologs possess conserved catalytic residues, but have distinct differences in their RNA recognition motifs from eukaryotic NSun6s. Until now, the biochemical properties and functions of archaeal NSun6 homologs were unknown. Read More

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December 2018
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Immune system stimulation increases dietary threonine requirements for protein deposition in growing pigs.

J Anim Sci 2018 Dec 12. Epub 2018 Dec 12.

Department of Animal and Food Sciences, Texas Tech University, Lubbock, Texas.

Previous studies have reported an increase in the utilization of threonine (Thr) during immune system stimulation (ISS). However, increased utilization of an amino acid (AA) during ISS may not reflect an increased dietary requirement, as endogenous sources may supply AA to meet the need for enhanced utilization. The current study evaluated the impact of ISS on components of dietary Thr requirements, i. Read More

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December 2018

ModL: exploring and restoring regularity when testing for positive selection.

Bioinformatics 2018 Dec 12. Epub 2018 Dec 12.

Department of Mathematics and Statistics, Dalhousie University, Halifax, NS, Canada.

Motivation: Likelihood ratio tests are commonly used to test for positive selection acting on proteins. They are usually applied with thresholds for declaring a protein under positive selection determined from a chi-square or mixture of chi-square distributions. While it is known that such distributions are not strictly justified due to the statistical irregularity of the problem, the hope has been that the resulting tests are conservative and do not lose much power in comparison with the same test using the unknown, correct threshold. Read More

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December 2018

DNA demethylation facilitates the specific transcription of the mouse X-linked Tsga8 gene in round spermatids.

Biol Reprod 2018 Dec 12. Epub 2018 Dec 12.

Department of Medical Genetics and Division of Human Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.

Some X-linked genes necessary for spermiogenesis are specifically activated in the post-meiotic germ cells. However, the regulatory mechanism about this activation is not clearly understood. Here, we examined the potential mechanism controlling the transcriptional activation of the mouse testis specific gene A8 (Tsga8) gene in round spermatids. Read More

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December 2018

Cancer stem cells in relation to treatment.

Jpn J Clin Oncol 2018 Dec 12. Epub 2018 Dec 12.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

The classical cancer therapies, including chemotherapy and radiation therapy, can initially show good results and tumor shrinkage; however, for most cancer patients disease recurrence is a common event. This tumor regrowth following therapy is now thought to depend on a small population of cancer stem cells (CSCs), which, similar to other stem cells, have the capacity for self-renewal and multipotent differentiation. Cancer stem cells have been identified based on cell surface protein expression in many tumor types, and for all diseases studied, this specific cell population is required for serial transplantation in animal models. Read More

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December 2018

miR172 Regulates both Vegetative and Reproductive Development in the Perennial Woody Plant Jatropha curcas.

Plant Cell Physiol 2018 Dec;59(12):2549-2563

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan, China.

Jatropha curcas is a promising feedstock for biofuel production because its oil is highly suitable for processing bio-jet fuels and biodiesel. However, Jatropha exhibits a long juvenile stage in subtropical areas. miR172, a conserved small non-protein-coding RNA molecule with 21 nucleotides, regulates a wide range of developmental processes. Read More

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December 2018

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.

Authors:
Naomi Walsh Han Zhang Paula L Hyland Qi Yang Evelina Mocci Mingfeng Zhang Erica J Childs Irene Collins Zhaoming Wang Alan A Arslan Laura Beane-Freeman Paige M Bracci Paul Brennan Federico Canzian Eric J Duell Steven Gallinger Graham G Giles Michael Goggins Gary E Goodman Phyllis J Goodman Rayjean J Hung Charles Kooperberg Robert C Kurtz Núria Malats Loic LeMarchand Rachel E Neale Sara H Olson Ghislaine Scelo Xiao O Shu Stephen K Van Den Eeden Kala Visvanathan Emily White Wei Zheng Demetrius Albanes Gabriella Andreotti Ana Babic William R Bamlet Sonja I Berndt Ayelet Borgida Marie-Christine Boutron-Ruault Lauren Brais Paul Brennan Bas Bueno-de-Mesquita Julie Buring Kari G Chaffee Stephen Chanock Sean Cleary Michelle Cotterchio Lenka Foretova Charles Fuchs J Michael M Gaziano Edward Giovannucci Michael Goggins Thilo Hackert Christopher Haiman Patricia Hartge Manal Hasan Kathy J Helzlsouer Joseph Herman Ivana Holcatova Elizabeth A Holly Robert Hoover Rayjean J Hung Vladimir Janout Eric A Klein Robert C Kurtz Daniel Laheru I-Min Lee Lingeng Lu Núria Malats Satu Mannisto Roger L Milne Ann L Oberg Irene Orlow Alpa V Patel Ulrike Peters Miquel Porta Francisco X Real Nathaniel Rothman Howard D Sesso Gianluca Severi Debra Silverman Oliver Strobel Malin Sund Mark D Thornquist Geoffrey S Tobias Jean Wactawski-Wende Nick Wareham Elisabete Weiderpass Nicolas Wentzensen William Wheeler Herbert Yu Anne Zeleniuch-Jacquotte Peter Kraft Donghui Li Eric J Jacobs Gloria M Petersen Brian M Wolpin Harvey A Risch Laufey T Amundadottir Kai Yu Alison P Klein Rachael Z Stolzenberg-Solomon

J Natl Cancer Inst 2018 Dec 12. Epub 2018 Dec 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.

Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. Read More

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December 2018

DNA damage and repair in the female germline: contributions to ART.

Hum Reprod Update 2018 Dec 12. Epub 2018 Dec 12.

Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW, Australia.

Background: DNA integrity and stability are critical determinants of cell viability. This is especially true in the female germline, wherein DNA integrity underpins successful conception, embryonic development, pregnancy and the production of healthy offspring. However, DNA is not inert; rather, it is subject to assault from various environment factors resulting in chemical modification and/or strand breakage. Read More

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December 2018

The Na+/H+ Exchanger Nhe1 Modulates Network Excitability via GABA Release.

Cereb Cortex 2018 Dec 12. Epub 2018 Dec 12.

Institute of Human Genetics, Jena University Hospital, Jena, Germany.

Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na+/H+ exchanger Nhe1, which uses the Na+ gradient to extrude H+, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1-positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. Read More

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December 2018
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Management of paediatric patients with medically-refractory Crohn's disease using Ustekinumab: A multi-centred cohort study.

J Crohns Colitis 2018 Dec 12. Epub 2018 Dec 12.

Division of Gastroenterology, Montreal Children's Hospital, Department of Paediatrics, McGill University, Montreal, Quebec, Canada.

Background: Ustekinumab (UST) is effective in the treatment of adults with moderate to severe Crohn's disease (CD). There is a paucity of data on its use in children.

Aim: To evaluate the response to UST in children with moderate to severe CD. Read More

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December 2018
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Silencing the ACAT1 Gene in Human SH-SY5Y Neuroblastoma Cells Inhibits the Expression of Cyclo-Oxygenase 2 (COX2) and Reduces β-Amyloid-Induced Toxicity Due to Activation of Protein Kinase C (PKC) and ERK.

Med Sci Monit 2018 Dec 12;24:9007-9018. Epub 2018 Dec 12.

Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China (mainland).

BACKGROUND Acyl-coenzymeA: cholesterol acyltransferase (ACAT) 1, a key enzyme converting excess free cholesterol to cholesterol esters, has been demonstrated to be associated with the pathogenesis of Alzheimer disease (AD). However, the mechanism underlying the protective role of ACAT1 blockage in AD progression remains elusive. MATERIAL AND METHODS Human neuroblastoma SH-SY5Y cells were treated for 24 h with increasing concentrations of aggregated Aβ₂₅₋₃₅ (5, 15, 25, and 45 μmol) with or without the ACAT1 siRNA pretreatment. Read More

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December 2018

Influence of Nutritional Management and Rehabilitation on Physical Outcome in Japanese Intensive Care Unit Patients: A Multicenter Observational Study.

Ann Nutr Metab 2018 Dec 12;74(1):35-43. Epub 2018 Dec 12.

Emergency and Critical Care Medicine, Tokushima University Graduate School, Tokushima, Japan.

Background: There is lack of evidence regarding nutritional management among intensive care unit (ICU) patients in a population with relatively low body mass index. Therefore, we conducted an observational study to assess the nutritional management in Japanese ICUs. Also, we investigated the impact of nutritional management and rehabilitation on physical outcome. Read More

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December 2018

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis.

Nephron 2018 Dec 12:1-11. Epub 2018 Dec 12.

Department of Nephrology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

Background/aims: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury.

Methods: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. Read More

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December 2018

Integrated proteome analyses of wheat glume and awn reveal central drought response proteins under water deficit conditions.

J Plant Physiol 2018 Nov 16;232:270-283. Epub 2018 Nov 16.

College of Life Science, Capital Normal University, 100048, Beijing, China. Electronic address:

Main Conclusion: Integrated proteome analyses revealed differentially accumulated proteins in the non-leaf green organs in wheat glume and awn that play important roles in photosynthesis and drought resistance. Two non-leaf green organs in wheat, glume and awn, have photosynthetic potential, contribute to grain yield, and also play roles in resistance to adverse conditions. We performed the first integrated proteome analysis of wheat glume and awn in response to water deficit. Read More

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November 2018

The antiviral mechanism of viperin and its splice variant in spring viremia of carp virus infected fathead minnow cells.

Fish Shellfish Immunol 2018 Dec 9. Epub 2018 Dec 9.

College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, 430070, China; Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention, Wuhan, 430070, China. Electronic address:

Viperin is known to play an important role in innate immune and its antiviral mechanisms are well demonstrated in mammals. Fish Viperin mediates antiviral activity against several viruses. However, little has been done to the underlying mechanism. Read More

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December 2018

A Renewable Source of Human Beige Adipocytes for Development of Therapies to Treat Metabolic Syndrome.

Cell Rep 2018 Dec;25(11):3215-3228.e9

Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA; School of Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04469, USA; Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA. Electronic address:

Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Read More

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December 2018
1 Read

CDK Phosphorylation of Translation Initiation Factors Couples Protein Translation with Cell-Cycle Transition.

Cell Rep 2018 Dec;25(11):3204-3214.e5

Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address:

Protein translation in eukaryotes is cell-cycle dependent, with translation rates more robust in G1 phase of the cell cycle than in mitosis. However, whether the fundamental cell-cycle control machinery directly activates protein translation during the G1/S cell-cycle transition remains unknown. Using the early divergent eukaryote Trypanosoma brucei as a model organism, we report that the G1 cyclin-dependent kinase CRK1 phosphorylates two translation initiation factors, eIF4E4 and PABP1, to promote the G1/S cell-cycle transition and global protein translation. Read More

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December 2018

Ten-Eleven Translocation Proteins Modulate the Response to Environmental Stress in Mice.

Cell Rep 2018 Dec;25(11):3194-3203.e4

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:

5-hydroxymethylcytosine (5hmC) is enriched in brain and has been recognized as an important DNA modification. However, the roles of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in stress-induced response have yet to be elucidated. Here, we show that chronic restraint stress (CRS) induced depression-like behavior in mice and resulted in a 5hmC reduction in prefrontal cortex (PFC). Read More

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December 2018

Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.

Cell Rep 2018 Dec;25(11):3136-3147.e5

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Read More

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December 2018

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Cell Rep 2018 Dec;25(11):3123-3135.e6

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban 4041, South Africa. Electronic address:

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. Read More

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December 2018

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse.

Cell Rep 2018 Dec;25(11):3110-3122.e6

Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Católica de Chile, Region Metropolitana, Santiago 8331150, Chile. Electronic address:

Complete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8-a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins-is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Read More

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December 2018

TMED2 Potentiates Cellular IFN Responses to DNA Viruses by Reinforcing MITA Dimerization and Facilitating Its Trafficking.

Cell Rep 2018 Dec;25(11):3086-3098.e3

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

Mediator of IRF3 activation (MITA), also known as stimulator of interferon genes (STING), plays a vital role in the innate immune responses to cytosolic dsDNA. The trafficking of MITA from the ER to perinuclear vesicles is necessary for its activation of the downstream molecules, which lead to the production of interferons and pro-inflammatory cytokines. However, the exact mechanism of MITA activation remains elusive. Read More

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December 2018

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming.

Cell Rep 2018 Dec;25(11):3059-3073.e10

Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS, Fondazione Santa Lucia, Rome, Italy. Electronic address:

Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Read More

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December 2018
2 Reads

IGFBP7 Induces Differentiation and Loss of Survival of Human Acute Myeloid Leukemia Stem Cells without Affecting Normal Hematopoiesis.

Cell Rep 2018 Dec;25(11):3021-3035.e5

Department of Hematology, Cancer Center Amsterdam (CCA), Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands. Electronic address:

Leukemic stem cells (LSCs) are thought to be the major cause of the recurrence of acute myeloid leukemia (AML) due to their potential for self-renewal. To identify therapeutic strategies targeting LSCs, while sparing healthy hematopoietic stem cells (HSCs), we performed gene expression profiling of LSCs, HSCs, and leukemic progenitors all residing within the same AML bone marrow and identified insulin-like growth factor-binding protein 7 (IGFBP7) as differentially expressed. Low IGFBP7 is a feature of LSCs and is associated with reduced chemotherapy sensitivity. Read More

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December 2018
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Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.

Cell Rep 2018 Dec;25(11):2955-2962.e3

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Double homeobox (DUX) transcription factors are unique to eutherian mammals. DUX4 regulates expression of repetitive elements during early embryogenesis, but misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and translocations overexpressing the DUX4 double homeodomain cause B cell leukemia. Here, we report the crystal structure of the tandem homeodomains of DUX4 bound to DNA. Read More

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December 2018
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SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle.

Cell Rep 2018 Dec;25(11):2946-2954.e5

Molecular Biology of the Cell II, German Cancer Research Centre (DKFZ), DKFZ-Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) Alliance, 69120 Heidelberg, Germany. Electronic address:

Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. Read More

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December 2018

LTP suppression by protein synthesis inhibitors is NO-dependent.

Neuropharmacology 2018 Dec 9. Epub 2018 Dec 9.

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerovа 5A, 117485, Moscow, Russia.

For several decades, the ability of protein synthesis inhibitors (PSI) to suppress the long-term potentiation (LTP) of hippocampal responses is known. It is considered that mechanisms of such impairment are related to a cessation of translation and a delayed depletion of the protein pool required for maintenance of synaptic plasticity. The present study demonstrates that cycloheximide or anisomycin applications reduce amplitudes of the field excitatory postsynaptic potentials as well as the presynaptically mediated form of plasticity, the paired-pulse facilitation after LTP induction in neurons of the CA1 area of hippocampus. Read More

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December 2018

Conformational stability and dynamics of the cancer-associated isoform Δ133p53β are modulated by p53 peptides and p53-specific DNA.

FASEB J 2018 Dec 12:fj201801973R. Epub 2018 Dec 12.

Basic Science Program, Leidos Biomedical Research, Inc., Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland, USA; and.

p53 is a tumor suppressor protein that maintains genome stability, but its Δ133p53β and Δ160p53β isoforms promote breast cancer cell invasion. The sequence truncations in the p53 core domain raise key questions related to their physicochemical properties, including structural stabilities, interaction mechanisms, and DNA-binding abilities. Herein, we investigated the conformational dynamics of Δ133p53β and Δ160p53β with and without binding to p53-specific DNA by using molecular dynamics simulations. Read More

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December 2018

Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA-540 expression.

FASEB J 2018 Dec 12:fj201802015R. Epub 2018 Dec 12.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Levels of augmenter of liver regeneration (ALR), a multifunctional protein, are reduced in steatohepatitis. ALR depletion from ALR /Alb-Cre [ALR-L-knockout (KO)] mouse causes robust steatosis and apoptosis of hepatocytes, and pericellular fibrosis between 1 and 2 wk postbirth. Steatosis regresses by 4 wk upon reappearance of ALR-expressing hepatocytes. Read More

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December 2018

Photo-induced tyrosine side chain fragmentation in IgG4-Fc: mechanisms and solvent isotope effects.

Mol Pharm 2018 Dec 12. Epub 2018 Dec 12.

Immunoglobulin gamma (IgG) monoclonal antibodies (mAbs) are glycoproteins that have emerged as powerful and promising protein therapeutics. During the process of production, storage and transportation, exposure to ambient light is inevitable, which can cause protein physical and chemical degradation. For mechanistic studies of photo-degradation, we have exposed IgG4-Fc to UV light. Read More

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December 2018
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Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target.

ACS Chem Neurosci 2018 Dec 12. Epub 2018 Dec 12.

While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials and GPR88 endogenous ligands remain unknown. Read More

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December 2018

Structure-activity relationships of the bacteriocin bactofencin A and its interaction with bacterial membrane.

ACS Infect Dis 2018 Dec 12. Epub 2018 Dec 12.

The antimicrobial peptide bactofencin A is an unmodified non-pediocin-like bacteriocin that inhibits several clinically relevant pathogens including Listeria monocytogenes and Staphylococcus aureus. Here we report the synthesis and structure-activity relationship studies of bactofencin A and novel analogs thereof. Synthetic bactofencin A was a potent inhibitor of L. Read More

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December 2018

[Influence of HPV infection on cell cycle regulation in epithelial cell alterations of cervix uteri: Immunohistochemical and in situ hybridization observations].

Magy Onkol 2018 Dec 25;62(4):264-271. Epub 2018 Nov 25.

Daganatpatológiai Központ, Országos Onkológiai Intézet, Budapest, Hungary.

The HPV16 E6 DNA incorporation into the cervical epithelial cell genome was determined. In addition, using p16, p21 and p27 protein immunohistochemistry, we intended to present how the normal cell cycle machinery was disturbed in cervical epithelial cells. In CIN1 the epithelial cells are transformed into koilocytes, p16 is not expressed. Read More

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December 2018

Impacts and interactions of organic compounds with chlorine sanitizer in recirculated and reused produce processing water.

PLoS One 2018 12;13(12):e0208945. Epub 2018 Dec 12.

U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Environmental Microbiology and Food Safety Laboratory, Beltsville, Maryland, United States of America.

Water conservation and economics dictate that fresh produce processors reuse/recirculate the process water. However, the ensuing accumulation of organic matter in water depletes the chlorine sanitizer required for food safety. In this study, we comprehensively investigated chemical compounds that are responsible for water quality in relation to chemical oxygen demand (COD) and chlorine demand (CLD), the two most critical factors associated with water treatment and chlorine replenishment. Read More

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December 2018

Gene network analysis of poplar root transcriptome in response to drought stress identifies a PtaJAZ3PtaRAP2.6-centered hierarchical network.

PLoS One 2018 12;13(12):e0208560. Epub 2018 Dec 12.

Forest Resources and Environmental Science, Michigan Technological University, Houghton, MI, United States of America.

Using time-series transcriptomic data from poplar roots undergoing polyethylene glycol (PEG)-induced drought stress, we built a genetic network model of the involved putative molecular responses. We found that the network resembled a hierarchical structure. The highest hierarchical level in this structure is occupied by 9 genes, which we called superhubs because they were primarily connected to 18 hub genes, which are then connected to 2,934 terminal genes. Read More

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December 2018

Dietary total antioxidant capacity (TAC) among candidates for coronary artery bypass grafting (CABG) surgery: Emphasis to possible beneficial role of TAC on serum vitamin D.

PLoS One 2018 12;13(12):e0208806. Epub 2018 Dec 12.

Department of Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Aims: Recently, the clinical importance of total antioxidant capacity (TAC) and its protective role against several chronic diseases like cardiovascular disease, osteoporosis and several types of cancers has been reported. However, its association with cardio-metabolic risk factors among patients candidate for coronary artery bypass graft surgery (CABG) has not been evaluated yet. CABG is associated with increased oxidative stress and free radicals; so, the current study was aimed to evaluate the potential association of TAC with cardiovascular risk factors among patients candidate for CABG. Read More

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December 2018
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