5,494,265 results match your criteria Cellular and molecular life sciences : CMLS[Journal]

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Effects of irradiation and leukoreduction on down regulation of CXCL-8 and storage lesion in stored canine whole blood.

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

Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.

White blood cells (WBCs) and storage period are the main factors of transfusion reactions. In the present study, cytokine/chemokine concentrations after leukoreduction (LR) and irradiation (IR) in stored canine whole blood were measured. Red blood cell (RBC) storage lesion caused by IR and LR were also compared. Read More

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December 2018
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[Cobalamin deficiency in dogs and cats].

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018 Oct 12;46(5):309-314. Epub 2018 Dec 12.

Cobalamin is a member of the B-group of vitamins and a cofactor for metabolic processes like nucleic acid synthesis, amino acid synthesis, and the citric acid cycle. Mammals are unable to synthesize cobalamin and therefore rely on adequate food intake. Cobalamin absorption is a complex process in the stomach, duodenum, and ileum, requiring a functional exocrine pancreas. Read More

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October 2018
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[Diagnostic value of the BRAF variant V595E in urine samples, smears and biopsies from canine transitional cell carcinoma].

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018 Oct 12;46(5):289-295. Epub 2018 Dec 12.

Objective: Transitional cell carcinoma (TCC) is the most common malignant tumour of the canine urinary tract. Previously, the mutation of the BRAF gene V595E was identified in approximately 85 % of canine TCC cases by DNA sequencing of TCC tumour cells, both in frozen and paraffin-embedded tissue sections, as well as in urine. The objective of this study was to establish these methods in cytological smears and to investigate the prevalence of BRAF mutation V595E in canine TCC in our cohort of patients. Read More

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October 2018
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Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1.

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

Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Read More

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December 2018

Xenotransplantation: Progress Along Paths Uncertain from Models to Application.

ILAR J 2018 Dec 12. Epub 2018 Dec 12.

Translational Medicine and The Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. In principle, use of animals such as pigs as a source of transplants would allow transplantation to exert a vastly greater impact than allotransplantation on medicine and public health. Read More

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December 2018
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Pancreatic Islet Transplantation in Humans: Recent Progress and Future Directions.

Endocr Rev 2018 Dec 12. Epub 2018 Dec 12.

Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.

Pancreatic islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin deficient diabetes. Recent progress in techniques for islet isolation, islet culture, and peri-transplant management of the islet transplant recipient have resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or sub-total pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent or ameliorate post-surgical diabetes, and for patients previously experiencing painful recurrent acute or chronic pancreatitis, quality-of-life is substantially improved. Read More

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December 2018
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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

MEASUREMENT OF EMF EXPOSURE AROUND SMALL CELL BASE STATION SITES.

Radiat Prot Dosimetry 2018 Nov 29. Epub 2018 Nov 29.

Alphawave, 3 Meson Street, Technopark, Stellenbosch, South Africa.

As mobile network technologies and usage change, mobile network cells have become smaller to meet the increased demand for data throughput. Small cell base stations are frequently used as a mobile network deployment method and are predominantly installed to service areas with a high density of people and to cover a small geographical area. Various measurement programs of the electromagnetic field (EMF) exposure have been conducted around base stations in general and these results have been published. Read More

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November 2018

The Cerebral Cortex is Bisectionally Segregated into Two Fundamentally Different Functional Units of Gyri and Sulci.

Cereb Cortex 2018 Dec 12. Epub 2018 Dec 12.

Cortical Architecture Imaging and Discovery Lab, Department of Computer Science and Bioimaging Research Center, The University of Georgia, Athens, GA, USA.

The human cerebral cortex is highly folded into diverse gyri and sulci. Accumulating evidences suggest that gyri and sulci exhibit anatomical, morphological, and connectional differences. Inspired by these evidences, we performed a series of experiments to explore the frequency-specific differences between gyral and sulcal neural activities from resting-state and task-based functional magnetic resonance imaging (fMRI) data. 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

Evidence that a catalytic glutamate and an 'Arginine Toggle' act in concert to mediate ATP hydrolysis and mechanochemical coupling in a viral DNA packaging motor.

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

Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.

ASCE ATPases include ring-translocases such as cellular helicases and viral DNA packaging motors (terminases). These motors have conserved Walker A and B motifs that bind Mg2+-ATP and a catalytic carboxylate that activates water for hydrolysis. Here we demonstrate that Glu179 serves as the catalytic carboxylate in bacteriophage λ terminase and probe its mechanistic role. Read More

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December 2018

The role of glutamine metabolism for host defense against Mycobacterium tuberculosis infection.

J Infect Dis 2018 Dec 12. Epub 2018 Dec 12.

Radboud university medical center, Department of Internal Medicine and Radboud Center of Infectious Diseases, Nijmegen, the Netherlands.

Background: Rewiring cellular metabolism is important for activation of immune cells during host defense against Mycobacterium tuberculosis. Glutamine has been implicated as an immunomodulatory nutrient, but its role in response to M. tuberculosis is unknown. Read More

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December 2018
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Characterization of the Inner and Outer Fiber Layers in the Developing Cerebral Cortex of Gyrencephalic Ferrets.

Cereb Cortex 2018 Dec 12. Epub 2018 Dec 12.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

Changes in the cerebral cortex of mammals during evolution have been of great interest. Ferrets, monkeys, and humans have more developed cerebral cortices compared with mice. Although the features of progenitors in the developing cortices of these animals have been intensively investigated, those of the fiber layers are still largely elusive. Read More

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December 2018

Haemodynamic stress-induced breaches of the arterial intima trigger inflammation and drive atherogenesis.

Eur Heart J 2018 Dec 11. Epub 2018 Dec 11.

INSERM U1148, Laboratory for Vascular Translational Science (LVTS), DHU FIRE, University Paris Diderot, Sorbonne Paris Cité, 46 rue Henri Huchard, Paris, France.

Aims: Inflammatory mediators, including blood cells and their products, contribute critically to atherogenesis, but the igniting triggers of inflammation remain elusive. Atherosclerosis develops at sites of flow perturbation, where the enhanced haemodynamic stress could initiate the atherogenic inflammatory process due to the occurrence of mechanic injury. We investigated the role of haemodynamic stress-induced breaches, allowing the entry of blood cells in the arterial intima, in triggering inflammation-driven atherogenesis. 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

Backscattered electron imaging of high pressure frozen soybean root nodules visualizes formation of symbiosome membranes.

Microscopy (Oxf) 2018 Dec 12. Epub 2018 Dec 12.

Comprehensive Analysis Center for Science, Saitama University, Saitama, Japan.

High-pressure frozen soybean root nodules were fractured and backscattered electron images were obtained from uncoated samples in a low vacuum scanning electron microscope equipped with a cryo-transfer system. Structures of infected cells were well preserved: numerous symbiosomes, as well as nuclei, plastids and mitochondria were observed without ice crystal damage. After appropriate sublimation of water, bacteria included in symbiosomes were visualized. 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

A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease.

Hum Mol Genet 2018 Dec 12. Epub 2018 Dec 12.

KU Leuven - Department of Neurosciences, Laboratory for Neuroimmunology, B-3000 Leuven, Belgium.

The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization. Read More

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December 2018

Safety Considerations When Working with Humanized Animals.

ILAR J 2018 Dec 12. Epub 2018 Dec 12.

Unit for Laboratory Animal Medicine, University of Michigan Medical School in Ann Arbor, Michigan.

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. 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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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

Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection.

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

Faculty of Medicine and Biomedical Sciences, MAHSA University, Saujana Putra Campus, Jenjarum,

Objective: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. Read More

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December 2018

Comparative Study of MSCA-1 and CD146 Isolated Periosteal Cell Subpopulations.

Cell Physiol Biochem 2018 12;51(3):1193-1206. Epub 2018 Dec 12.

Department of Oral and Maxillofacial Surgery of the University Hospital of Tübingen, Tübingen,

Background/aims: Periosteal tissue is a valuable source of multipotent stem cells for bone tissue engineering. To characterize these cells in detail, we generated an immortalized human cranial periosteal cell line and observed an increased MSCA-1 and CD146 expression, as well as an earlier and stronger mineralization compared to the parental cells. Further, we detected a higher osteogenic potential of MSCA-1high compared to MSCA-1low cranial periosteal cell (CPC) fractions. 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

Self-assembled CpG oligodeoxynucleotides conjugated hollow gold nanospheres to enhance cancer-associated immunostimulation.

Colloids Surf B Biointerfaces 2018 Dec 3;175:248-255. Epub 2018 Dec 3.

Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, PR China. Electronic address:

To realize efficiently cellular uptake and enhance the immunostimulation, thiolated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) were self-assembled on hollow gold nanospheres (HGNs) to form CpG-HGNs. The cellular uptake of CpG-HGNs in immune cells was studied in RAW 264.7 cells. Read More

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December 2018

Photothermally controlled drug release system with high dose loading for synergistic chemo-photothermal therapy of multidrug resistance cancer.

Colloids Surf B Biointerfaces 2018 Dec 5;175:239-247. Epub 2018 Dec 5.

Laboratory of Environmental Sciences and Technology, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang 830011, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Read More

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December 2018

1,25‑Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b.

Int Immunopharmacol 2018 Dec 9;67:106-118. Epub 2018 Dec 9.

Department of Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China; Key Laboratory of Tumor Prevention and Treatment of Heilongjiang Province, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China; Institute of Neural Tissue Engineering, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China. Electronic address:

Macrophages are highly plastic cells. Depending on stimulation, macrophages rapidly polarize to functionally distinct phenotypes that are involved in the pathogenesis of inflammatory bowel disease (IBD). 1,25‑Dihydroxyvitamin D (1,25(OH)D) has immunomodulatory activity, and 1,25(OH)D deficiency is correlated with autoimmune diseases, especially IBD. Read More

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December 2018

Axon-Seq Decodes the Motor Axon Transcriptome and Its Modulation in Response to ALS.

Stem Cell Reports 2018 Dec;11(6):1565-1578

Department of Neuroscience, Karolinska Institutet, Stockholm 171 77, Sweden. Electronic address:

Spinal motor axons traverse large distances to innervate target muscles, thus requiring local control of cellular events for proper functioning. To interrogate axon-specific processes we developed Axon-seq, a refined method incorporating microfluidics, RNA sequencing (RNA-seq), and bioinformatic quality control. We show that the axonal transcriptome is distinct from that of somas and contains fewer genes. Read More

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December 2018

Single-Cell Transcriptome Profiling of Mouse and hESC-Derived Pancreatic Progenitors.

Stem Cell Reports 2018 Dec;11(6):1551-1564

Diabetes Research Group, BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada; Departments of Surgery and Cellular and Physiological Sciences, University of British Columbia, 950 28(th) Avenue West, Vancouver, BC V5Z4H4, Canada. Electronic address:

Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing β cells for diabetes treatment. A greater understanding of how β cells form during embryonic development will improve current hESC differentiation protocols. All pancreatic endocrine cells, including β cells, are derived from Neurog3-expressing endocrine progenitors. Read More

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December 2018

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking.

Stem Cell Reports 2018 Dec;11(6):1365-1377

Global Safety Pharmacology, Non-Clinical Safety, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Read More

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December 2018

Screening-Based Chemical Approaches to Unravel Stem Cell Biology.

Authors:
Shuibing Chen

Stem Cell Reports 2018 Dec;11(6):1312-1323

Department of Surgery and Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address:

Cell-permeable compounds provide a convenient and efficient approach to manipulate biological processes. A number of compounds controlling stem cell self-renewal, survival, differentiation, and reprogramming have been identified through high-throughput/content screens. Using these powerful chemical tools, strategies have been developed to direct human pluripotent stem cell (hPSC) differentiation to functional cells. Read More

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December 2018

Perspectives on the Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Biomedical Research.

Stem Cell Reports 2018 Dec;11(6):1306-1311

Department of Anatomy and Embryology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands. Electronic address:

Cardiovascular disease is still a major cause of ill-health and mortality, heart failure and arrhythmia being among the causes of sudden cardiac death. There are few drugs available for treatment or prevention and it remains difficult to predict who will develop these conditions, even when disease-causing mutations or associated gene variants are identified in individuals or families. This is in part because widely used rodent models may not fully capture the physiology of the human heart. Read More

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December 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

IP Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca to Lysosomes.

Cell Rep 2018 Dec;25(11):3180-3193.e7

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. Electronic address:

Inositol 1,4,5-trisphosphate (IP) receptors (IPRs) allow extracellular stimuli to redistribute Ca from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H-ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca released by all IPR subtypes, but not Ca entering cells through store-operated Ca entry (SOCE). A low-affinity Ca sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca] during IP-evoked Ca release, but not during SOCE. Read More

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December 2018

Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1.

Cell Rep 2018 Dec;25(11):3169-3179.e7

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

Importins mediate transport from synapse to soma and from cytoplasm to nucleus, suggesting that perturbation of importin-dependent pathways should have significant neuronal consequences. A behavioral screen on five importin α knockout lines revealed that reduced expression of importin α5 (KPNA1) in hippocampal neurons specifically decreases anxiety in mice. Re-expression of importin α5 in ventral hippocampus of knockout animals increased anxiety behaviors to wild-type levels. Read More

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December 2018

Dopamine Cells Differentially Regulate Striatal Cholinergic Transmission across Regions through Corelease of Dopamine and Glutamate.

Cell Rep 2018 Dec;25(11):3148-3157.e3

Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address:

The balance of dopamine and acetylcholine in the dorsal striatum is critical for motor and learning functions. Midbrain dopamine cells and local cholinergic interneurons (ChIs) densely innervate the striatum and have strong reciprocal actions on each other. Although dopamine inputs regulate ChIs, the functional consequences of dopamine neuron activity across dorsal striatal regions is poorly understood. 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
3 Reads

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
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Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria.

Cell Rep 2018 Dec;25(11):3099-3109.e3

Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore. Electronic address:

Inflammation-induced disappearance of tissue-resident macrophages represents a key pathogen defense mechanism. Using a model of systemic blood-stage malaria, we studied the dynamics of tissue-resident macrophages in multiple organs to determine how they are depleted and refilled during the course of disease. We show that Plasmodium infection results in a transient loss of embryonically established resident macrophages prior to the parasitemia peak. 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
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Magnitude of Therapeutic STING Activation Determines CD8 T Cell-Mediated Anti-tumor Immunity.

Cell Rep 2018 Dec;25(11):3074-3085.e5

Aduro Biotech, Inc., Berkeley, CA 94710, USA. Electronic address:

Intratumoral (IT) STING activation results in tumor regression in preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate STING agonist ADU-S100 (S100) is used in an IT dosing regimen optimized for adaptive immunity to uncover requirements for a T cell-driven response compatible with checkpoint inhibitors (CPIs). In contrast to high-dose tumor ablative regimens that result in systemic S100 distribution, low-dose immunogenic regimens induce local activation of tumor-specific CD8 effector T cells that are responsible for durable anti-tumor immunity and can be enhanced with CPIs. Read More

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December 2018
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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
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Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.

Cell Rep 2018 Dec;25(11):3047-3058.e4

Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address:

Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. Read More

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December 2018

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.

Cell Rep 2018 Dec;25(11):3036-3046.e6

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA. Electronic address:

IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also a risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles of IL-10 in inflammation and colon cancer is unknown. We report here that inflammation induces the accumulation of CD11bGr1 myeloid-derived suppressor cells (MDSCs) that express high levels of IL-10 in colon tissue. Read More

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December 2018

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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