1,677,959 results match your criteria Biology And Environment-proceedings Of The Royal Irish Academy[Journal]


Rare case of an oligospermic male with 46,XX/46,XY tetragametic chimerism.

Andrologia 2019 Apr 17:e13290. Epub 2019 Apr 17.

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Chimerism, a rare human disorder, is assumed to be the result of an amalgamation of two separate zygotes in a single embryo. Studies have shown that the phenotypic spectrum of chimerism is variable and there is no definite genotype-phenotype correlation in patients with chimerism, therefore a majority of cases might remain undiagnosed. This study aims to investigate the possible mechanism of the chimerism in a 46,XX/46,XY infertile and phenotypically normal male, with 46,XX blood karyotype and normal spermatogenesis. Read More

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http://dx.doi.org/10.1111/and.13290DOI Listing

Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors.

Nature 2019 Apr 17. Epub 2019 Apr 17.

Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.

CRISPR-Cas base editor technology enables targeted nucleotide alterations and is being rapidly deployed for research and potential therapeutic applications. The most widely used base editors induce DNA cytosine (C) deamination with rat APOBEC1 (rAPOBEC1) enzyme, which is targeted by a linked Cas protein-guide RNA (gRNA) complex. Previous studies of cytosine base editor (CBE) specificity have identified off-target DNA edits in human cells. Read More

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http://dx.doi.org/10.1038/s41586-019-1161-zDOI Listing
April 2019
1 Read

IL1RN Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population.

Chemotherapy 2019 Apr 17:1-8. Epub 2019 Apr 17.

Department of Radiotherapy, Shaanxi Provincial Cancer Hospital Affiliated to Medical College, Xi'an Jiaotong University, Xi'an, China,

Background: Recent evidence suggested that IL1RN (interleukin-1 receptor antagonist) polymorphisms increased the susceptibility to cancers. The present study aimed to evaluate whether IL1RN was related to esophageal cancer susceptibility in a Northwest Han Chinese population.

Methods: The case-control study was conducted on 384 esophageal cancer patients and 499 healthy controls. Read More

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http://dx.doi.org/10.1159/000496400DOI Listing

Microwave thermal ablation using CT-scanner for predicting the variation of ablated region over time: advantages and limitations.

Phys Med Biol 2019 Apr 17. Epub 2019 Apr 17.

Technical Unit of Radiation Biology and Human Health, ENEA, Casaccia Research Centre, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Rome, Rome, ITALY.

This study aims at investigating in real-time the structural and dynamical changes occurring in an ex-vivo tissue during a microwave thermal ablation (MTA) treatment. The proposed set-up was based on ex vivo liver tissue inserted in a specific box, in which 3 fibre-optic (FO) temperature probes were introduced to measure the temperature increase over time. Computed Tomography (CT) imaging technique was exploited to experimentally study in real-time the Hounsfield Units (HU) modification occurring during MTA. Read More

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http://dx.doi.org/10.1088/1361-6560/ab1a67DOI Listing

Halogenated flame retardants in mangrove sediments from the Pearl River Estuary, South China: Comparison with historical data and correlation with microbial community.

Chemosphere 2019 Apr 11;227:315-322. Epub 2019 Apr 11.

State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, 510640, China.

Polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCDD) and dechlorane plus (DP) were measured in sediments collected from three mangrove wetlands of the Pearl River Estuary (PRE) in South China. This study aims to investigate the distribution of these halogenated flame retardants (HFRs) and the correlations between HFRs and microbial community structure in mangrove sediments. Concentrations of PBDEs, DBDPE, BTBPE, TBBPA, HBCDD and DP in mangrove sediments ranged from 6. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2019.04.075DOI Listing

Four new guaiane sesquiterpenoids from agarwood of Aquilaria filaria.

Fitoterapia 2019 Apr 14. Epub 2019 Apr 14.

Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, PR China. Electronic address:

Six 8,12-epoxyguaiane sesquiterpenes (1-6), together with two known 2-(2-phenylethyl)chromone derivatives (7-8) were isolated from agarwood originating from Aquilaria filaria. Their structures were established by spectroscopic methods including IR, HRESIMS, 1D, and 2D NMR, and comparison with the published data. The absolute configuration of compound 1 was unambiguously determined by quantum chemical calculation of the electronic circular dichroism (ECD) spectrum. Read More

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http://dx.doi.org/10.1016/j.fitote.2019.04.007DOI Listing

Cytotoxic effect of aqueous ethanolic extract of Luffa cylindrica leaves on cancer stem cells CD44/24 in breast cancer patients with various molecular sub-types using tissue samples in vitro.

J Ethnopharmacol 2019 Apr 14:111877. Epub 2019 Apr 14.

Medical Research Department, National Institute of Occupational Safety and Health, Egypt. Electronic address:

Ethnopharmacological Relevance: Luffa cylindrica (L.) M.Roem is a climbing plant its parts have been used as traditional medicine for the treatment of different types of diseases including diarrhea, inflammation, cancer and viral infections. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111877DOI Listing

Iron regulatory protein is involved in the immune defense of the Chinese mitten crab Eriocheir sinensis.

Fish Shellfish Immunol 2019 Apr 14. Epub 2019 Apr 14.

Laboratory of Invertebrate Immunological Defense and Reproductive Biology, School of Life Sciences, East China Normal University, Shanghai, China. Electronic address:

Iron homeostasis is vital to organismal health; it is maintained by the iron regulatory protein (IRP)-iron-responsive element (IRE) signaling pathway. In the Chinese mitten crab Eriocheir sinensis, EsFer-1 and EsFer-2 reportedly have a putative IRE, but an IRP has not yet been identified. In this study, we successfully amplified the full-length cDNA of EsIRP using gene cloning and rapid amplification of cDNA ends techniques. Read More

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http://dx.doi.org/10.1016/j.fsi.2019.04.041DOI Listing

Two alpha-2 macroglobulin from Portunus trituberculatus involved in the prophenoloxidase system, phagocytosis and regulation of antimicrobial peptides.

Fish Shellfish Immunol 2019 Apr 14. Epub 2019 Apr 14.

School of Marine Science, Ningbo University, Zhejiang, Ningbo, 315211, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. Electronic address:

Alpha-2 macroglobulin (A2M) is a ubiquitous protease inhibitor involved in the innate host defense system. Herein, two distinct A2M genes (designated as PtA2M-1 and PtA2M-2, respectively) were isolated from the swimming crab Portunus trituberculatus. PtA2M-1 and PtA2M-2 encoded proteins with 1541 or 1516 amino acids, respectively, containing the typically functional domains of A2M. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10504648193027
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http://dx.doi.org/10.1016/j.fsi.2019.04.033DOI Listing
April 2019
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The evolution of proteome: from the primeval to the very dawn of LUCA.

Biosystems 2019 Apr 14. Epub 2019 Apr 14.

Theoretical Biology Group, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México CDMX, C.P. 04510, Mexico. Electronic address:

The attempt to delineate the essential features that characterized life in its beginnings and the understanding of how those features evolved, represent important scientific challenges. While there have been varied efforts in the elucidation of how the first biomolecules arose from a prebiotic environment, there remains important gaps towards the characterization of the complete repertoire of the Last Universal Common Ancestor (LUCA). We portray a step-wise proteome evolution, by looking at the phenotype encoded by each one of the genetic codes that were appearing along evolution, beginning with the primeval genetic code and then with two intermediate Extended RNA codes, which finally shaped the current Standard Genetic Code (SGC). Read More

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http://dx.doi.org/10.1016/j.biosystems.2019.04.007DOI Listing

Reactive oxygen species as mediators of oxygen signaling during fetal-to-neonatal circulatory transition.

Free Radic Biol Med 2019 Apr 14. Epub 2019 Apr 14.

Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.

Reactive oxygen species (ROS) are frequently seen as pathological agents of oxidative stress. However, ROS are not always deleterious and can also act as cell signaling molecules. Vascular oxygen sensing and signaling during fetal-to-neonatal circulatory transition is a remarkable example of the physiological regulatory actions of ROS. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.008DOI Listing

Update on ERbeta.

J Steroid Biochem Mol Biol 2019 Apr 14. Epub 2019 Apr 14.

Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States.

ERbeta (ERβ) celebrated its 20th birthday in 2016 and although the overwhelming data in the literature indicate a role for this receptor in the control of epithelial proliferation, neurodegeneration and immune function, no ERβ agonists have yet made it to the clinics. This is the situation, despite the fact that very good safe ERβ agonists have been synthesized and at least one has been donated to the NIH for distribution to researchers, who want to study its possible clinical use. Clinical trials are ongoing for the use of ERβ agonists in prostate cancer and schizophrenia but even today reviewers of our grants still make comments like "The grant is excellent except that the focus of the grant is ERβ". Read More

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http://dx.doi.org/10.1016/j.jsbmb.2019.02.007DOI Listing

Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology.

J Am Coll Surg 2019 Apr 14. Epub 2019 Apr 14.

Department of Surgery, University of Arizona, Tucson, AZ.

Background: Overall incidence of CC is decreasing, however with increasing early-onset colon cancer (EOCC <50 y.o.). Read More

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http://dx.doi.org/10.1016/j.jamcollsurg.2019.03.022DOI Listing

Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ aggregation.

Food Chem Toxicol 2019 Apr 14. Epub 2019 Apr 14.

Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni 50 - 50134, Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy. Electronic address:

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aβ fibrillation, a main histopathological feature of Alzheimer's disease (AD). Read More

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http://dx.doi.org/10.1016/j.fct.2019.04.015DOI Listing

Transforming Growth Factor-β Signaling in Immunity and Cancer.

Immunity 2019 Apr;50(4):924-940

Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Transforming growth factor (TGF)-β is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Perturbations in TGF-β signaling underlie inflammatory diseases and promote tumor emergence. TGF-β is also central to immune suppression within the tumor microenvironment, and recent studies have revealed roles in tumor immune evasion and poor responses to cancer immunotherapy. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.024DOI Listing

Shared and Distinct Functions of Type I and Type III Interferons.

Immunity 2019 Apr;50(4):907-923

Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:

Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.025DOI Listing

IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation.

Immunity 2019 Apr;50(4):871-891

Laboratory of Immunoregulation and Infection, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.020DOI Listing

The Immunobiology of the Interleukin-12 Family: Room for Discovery.

Immunity 2019 Apr;50(4):851-870

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA. Electronic address:

The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, and IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection, and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.011DOI Listing
April 2019
3 Reads

The γ Family of Cytokines: Basic Biology to Therapeutic Ramifications.

Immunity 2019 Apr;50(4):832-850

Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Metabolic, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1674, USA. Electronic address:

The common cytokine receptor γ chain, γ, is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding γ results in X-linked severe combined immunodeficiency in humans, and γ family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.028DOI Listing

GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation.

Immunity 2019 Apr;50(4):796-811

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address:

The β common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.022DOI Listing

Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.

Cell Rep 2019 Apr;27(3):971-986.e9

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address:

Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193036
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http://dx.doi.org/10.1016/j.celrep.2019.03.047DOI Listing
April 2019
1 Read

A Comprehensive Drosophila melanogaster Transcription Factor Interactome.

Cell Rep 2019 Apr;27(3):955-970.e7

Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.071DOI Listing

Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control.

Cell Rep 2019 Apr;27(3):916-927.e5

Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Piazzale Tecchio 80, 80125 Naples, Italy. Electronic address:

Aggregation of α-synuclein and formation of inclusions are hallmarks of Parkinson's disease (PD). Aggregate formation is affected by cellular environment, but it has been studied almost exclusively in cell-free systems. We quantitatively analyzed α-synuclein inclusion formation and clearance in a yeast cell model of PD expressing either wild-type (WT) α-synuclein or the disease-associated A53T mutant from the galactose (Gal)-inducible promoter. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.081DOI Listing

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

Cell Rep 2019 Apr;27(3):900-915.e5

Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. Electronic address:

In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.077DOI Listing

Parallel Processing of Sound Dynamics across Mouse Auditory Cortex via Spatially Patterned Thalamic Inputs and Distinct Areal Intracortical Circuits.

Cell Rep 2019 Apr;27(3):872-885.e7

Department of Biology, University of Maryland, College Park, MD 20742, USA; Program in Neuroscience and Cognitive Science, University of Maryland, College Park, MD 20742, USA. Electronic address:

Natural sounds have rich spectrotemporal dynamics. Spectral information is spatially represented in the auditory cortex (ACX) via large-scale maps. However, the representation of temporal information, e. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.069DOI Listing

Overlapping Activities of Two Neuronal Splicing Factors Switch the GABA Effect from Excitatory to Inhibitory by Regulating REST.

Cell Rep 2019 Apr;27(3):860-871.e8

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Inflammation Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Otolaryngology-Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address:

A truncating mutation in the mouse Srrm4 gene, which encodes a neuronal splicing factor, causes alternative splicing defects selectively in the ear. The mechanism by which splicing is preserved in the brain of these mice is not known. Here, we show that SRRM3 limits the Srrm4 mutation-associated defects to the ear and that, in cortical neurons, overlapping SRRM3-SRRM4 activity regulates the development of interneuronal inhibition. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.072DOI Listing

IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from γδ T Cells.

Cell Rep 2019 Apr;27(3):835-846.e5

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address:

Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193042
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http://dx.doi.org/10.1016/j.celrep.2019.03.082DOI Listing
April 2019
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Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate.

Cell Rep 2019 Apr;27(3):820-834.e9

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Equipe 11 labellisée par la Ligue contre le Cancer, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France. Electronic address:

Inhibition of oxidative phosphorylation (OXPHOS) by 1-cyclopropyl-4-(4-[(5-methyl-3-(3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl]pyridin-2-yl)piperazine (BAY87-2243, abbreviated as B87), a complex I inhibitor, fails to kill human cancer cells in vitro. Driven by this consideration, we attempted to identify agents that engage in synthetically lethal interactions with B87. Here, we report that dimethyl α-ketoglutarate (DMKG), a cell-permeable precursor of α-ketoglutarate that lacks toxicity on its own, kills cancer cells when combined with B87 or other inhibitors of OXPHOS. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.058DOI Listing

PAR2-Mediated cAMP Generation Suppresses TRPV4-Dependent Ca Signaling in Alveolar Macrophages to Resolve TLR4-Induced Inflammation.

Cell Rep 2019 Apr;27(3):793-805.e4

Department of Pharmacology and Centre for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL, USA. Electronic address:

Alveolar macrophages (AMs), upon sensing pathogens, trigger host defense by activating toll-like receptor 4 (TLR4), but the counterbalancing mechanisms that deactivate AM inflammatory signaling and prevent lethal edema, the hallmark of acute lung injury (ALI), remain unknown. Here, we demonstrate the essential role of AM protease-activating receptor 2 (PAR2) in rapidly suppressing inflammation to prevent long-lasting injury. We show that thrombin, released during TLR4-induced lung injury, directly activates PAR2 to generate cAMP, which abolishes Ca entry through the TRPV4 channel. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.053DOI Listing

The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.

Cell Rep 2019 Apr;27(3):776-792.e7

Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address:

Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.063DOI Listing

Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.

Cell Rep 2019 Apr;27(3):750-761.e7

Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil. Electronic address:

Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.054DOI Listing

The Vomeronasal System Can Learn Novel Stimulus Response Pairings.

Cell Rep 2019 Apr;27(3):676-684.e6

Hebrew University Medical School, Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem 9112102, Israel. Electronic address:

Behavioral responses can be classified as innate or learned and are often mediated by distinct neuronal pathways. In many animals, chemical cues are crucial for directing behaviors, and multiple chemosensory subsystems serve this purpose. The major subsystems in vertebrates are the main olfactory system (MOS) and the vomeronasal system (VNS). Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.042DOI Listing

Endocannabinoid Signaling Mediates Local Dendritic Coordination between Excitatory and Inhibitory Synapses.

Cell Rep 2019 Apr;27(3):666-675.e5

Department of Biology, Science for Life, Utrecht University, 3584CH Utrecht, the Netherlands. Electronic address:

Dendritic inhibitory synapses are most efficient in modulating excitatory inputs localized on the same dendrite, but it is unknown whether their location is random or regulated. Here, we show that the formation of inhibitory synapses can be directed by excitatory synaptic activity on the same dendrite. We stimulated dendritic spines close to a GABAergic axon crossing by pairing two-photon glutamate uncaging with postsynaptic depolarization in CA1 pyramidal cells. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.078DOI Listing

Simultaneous Live Imaging of Multiple Endogenous Proteins Reveals a Mechanism for Alzheimer's-Related Plasticity Impairment.

Cell Rep 2019 Apr;27(3):658-665.e4

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

CaMKIIα is a central mediator of bidirectional synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). To study how CaMKIIα movement during plasticity is affected by soluble amyloid-β peptide oligomers (Aβ), we used FingR intrabodies to simultaneously image endogenous CaMKIIα and markers for excitatory versus inhibitory synapses in live neurons. Aβ blocks LTP-stimulus-induced CaMKIIα accumulation at excitatory synapses. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.041DOI Listing

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice.

Cell Rep 2019 Apr;27(3):649-657.e5

Program of Genetics, Texas A&M University, College Station, TX 77843, USA; Department of Biology, Texas A&M University, College Station, TX 77843, USA. Electronic address:

Every mammalian tissue exhibits daily rhythms in gene expression to control the activation of tissue-specific processes at the most appropriate time of the day. Much of this rhythmic expression is thought to be driven cell autonomously by molecular circadian clocks present throughout the body. By manipulating the daily rhythm of food intake in the mouse, we here show that more than 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.064DOI Listing

Risk of Severe Maternal Morbidity by Maternal Fertility Status: A US study in 8 States.

Am J Obstet Gynecol 2019 Apr 14. Epub 2019 Apr 14.

Center for Assisted Reproduction, Bedford, Texas.

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http://dx.doi.org/10.1016/j.ajog.2019.04.011DOI Listing

BZ043, a novel long-acting amylin analog, reduces gastric emptying, food intake, glycemia and insulin requirement in streptozotocin-induced diabetic rats.

Peptides 2019 Apr 14. Epub 2019 Apr 14.

National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil. Electronic address:

Amylin analogs are important adjunctive drugs in the treatment of diabetes mellitus. However, a dual therapy with insulin involves inconvenient multiple injections. Here we describe a novel n-terminal PEGylated human amylin analog - BZ043 - and its potential to improve the control of glycemia using lower doses of insulin. Read More

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http://dx.doi.org/10.1016/j.peptides.2019.04.004DOI Listing

Hemolymph C1qDC promotes the phagocytosis of oyster Crassostrea gigas hemocytes by interacting with the membrane receptor β-integrin.

Dev Comp Immunol 2019 Apr 14. Epub 2019 Apr 14.

Laboratory of Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China. Electronic address:

Phagocytosis constitutes a conserved cellular process for multicellular animals to ingest or engulf other cells or particles, which is facilitated by the use of opsonins to bind foreign particles and interact with cell surface receptors. The invertebrate secreted C1q domain-containing proteins (C1qDCs) have been reported to exhibit opsonic activity, while the detailed mechanisms of opsonization still remain unclear. In the present study, a C1qDC (designated as CgC1qDC-5) with opsonic activity was identified from the hemolymph of oyster Crassostrea gigas. Read More

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http://dx.doi.org/10.1016/j.dci.2019.04.004DOI Listing

Crystal Structure and Directed Evolution of Specificity of NlaIV Restriction Endonuclease.

J Mol Biol 2019 Apr 14. Epub 2019 Apr 14.

International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland. Electronic address:

Specificity engineering is challenging, and particularly difficult for enzymes that have the catalytic machinery and specificity determinants in close proximity. Restriction endonucleases have been used as a paradigm for protein engineering, but successful cases are rare. Here, we present the results of a directed evolution approach to the engineering of a dimeric, blunt end cutting restriction enzyme NlaIV (GGN/NCC). Read More

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http://dx.doi.org/10.1016/j.jmb.2019.04.010DOI Listing

Can Predicted Protein 3D-Structures Provide Reliable Insights into whether Missense Variants Are Disease-Associated?

J Mol Biol 2019 Apr 14. Epub 2019 Apr 14.

Structural Bioinformatics Group, Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, UK. Electronic address:

Knowledge of protein structure can be used to predict the phenotypic consequence of a missense variant. Since structural coverage of the human proteome can be roughly tripled to over 50% of the residues if homology-predicted structures are included in addition to experimentally-determined coordinates, it is important to assess the reliability of using predicted models when analysing missense variants. Accordingly, we assess whether a missense variant is structurally damaging by using experimental and predicted structures. Read More

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http://dx.doi.org/10.1016/j.jmb.2019.04.009DOI Listing

Serological and molecular evidence of Bartonella henselae in cats from Luanda city, Angola.

Acta Trop 2019 Apr 14. Epub 2019 Apr 14.

Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Oporto, Portugal; EpiUnit, Epidemiology Research Unit, Institute of Public Health of the University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Oporto, Portugal. Electronic address:

A total of 100 domestic cats from Luanda (Angola) were tested for the presence of antibodies against Bartonella henselae and spotted fever group of Rickettsia (SFGR) using indirect immunofluorescence assay (IFA). Molecular screening targeting the riboflavin synthase (ribC) gene for Bartonella and outer membrane protein B (ompB) gene for Rickettsia, using conventional PCR and sequencing was also performed in cat´s blood samples. Sixty-six percent of the cats from Luanda had IgG antibodies against Bartonella species but none of them had antibodies against SFGR. Read More

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http://dx.doi.org/10.1016/j.actatropica.2019.04.012DOI Listing

Detection of White Root Rot in Avocado Trees by Remote Sensing.

Plant Dis 2019 Apr 17:PDIS10181778RE. Epub 2019 Apr 17.

1 Department of Biochemistry and Molecular and Cellular Biology of Plants, Estación Experimental del Zaidín, Spanish National Research Council (CSIC), Profesor Albareda, 1, 18008, Granada, Spain.

White root rot, caused by the soilborne fungus , is an important constraint to production for a wide range of woody crop plants such as avocado trees. The current methods of detection of white root rot are based on microbial and molecular techniques, and their application at orchard scale is limited. In this study, physiological parameters provided by imaging techniques were analyzed by machine learning methods. Read More

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http://dx.doi.org/10.1094/PDIS-10-18-1778-REDOI Listing

Control of Wheat Fusarium Head Blight by Heat-Stable Antifungal Factor (HSAF) from .

Plant Dis 2019 Apr 17:PDIS09181517RE. Epub 2019 Apr 17.

1 Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety, State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, P.R. China.

Heat-stable antifungal factor (HSAF), which belongs to the polycyclic tetramate macrolactam family, was isolated from fermentations and exhibited inhibitory activities against a wide range of fungal pathogens. In this study, the antifungal activity of HSAF against in vitro and in vivo was investigated. A total of 50% of mycelial growth of was suppressed with 4. Read More

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http://dx.doi.org/10.1094/PDIS-09-18-1517-REDOI Listing

Using Hydrogel to Diversify the Adaptability and Applicability of Functional Nanoparticles: from Nanotech-Flavored Jellies to Artificial Enzymes.

Langmuir 2019 Apr 17. Epub 2019 Apr 17.

The use of hydrogel to accommodate nanoparticles is generally aimed at synergetic integration of the peculiar electronic, photonic, magnetic, mechanical, and chemical properties of the nanoparticles with the stimuli-response of the hydrogels into unprecedented, smart, collective functions. The intrinsic water-borne nature of hydrogels further endorses the significant implications of such nanocomposites in biology and medicine. This article will be an account with accent on how to introduce nanoparticles within a hydrogel and to utilize the hydrogel to assist the nanoparticles to adapt themselves into different environments with a large span of polarity ranging from orthodox aqueous media to unorthodox organic ones. Read More

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http://dx.doi.org/10.1021/acs.langmuir.9b00254DOI Listing

Loss of the vitamin D receptor in human breast cancer cells promotes epithelial to mesenchymal cell transition and skeletal colonisation.

J Bone Miner Res 2019 Apr 17. Epub 2019 Apr 17.

Bone Research Program, ANZAC Research Institute and Concord Medical School, The University of Sydney, Sydney, Australia.

Expression of the vitamin D receptor (VDR) is thought to be associated with neoplastic progression. However, the role of the VDR in breast cancer metastasis to bone, and the molecular mechanisms underlying this process are unknown. Employing a rodent model (female Balb/c nu/nu mice) of systemic metastasis, we here demonstrate that knock-down of the VDR strongly increases the metastatic potential of MDA-MB-231 human breast cancer cells to bone, resulting in significantly greater skeletal tumour burden. Read More

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http://dx.doi.org/10.1002/jbmr.3744DOI Listing

Investigations on the Role of the Fibrinolytic Pathway on Outflow Facility Regulation.

Invest Ophthalmol Vis Sci 2019 Apr;60(5):1571-1580

Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, United States.

Purpose: To understand the role and further dissect pathways downstream of tissue plasminogen activator (tPA) and the fibrinolytic pathway in modulating outflow facility.

Methods: Outflow facility of tissue plasminogen activator (Plat) knockout (KO) mice was determined and compared to that of wild-type (WT) littermates. Gene expression of urokinase plasminogen activator (Plau), plasminogen activator inhibitor (Pai-1), plasminogen (Plg), and matrix metalloproteinases (Mmp-2, -9, and -13) was measured in angle tissues. Read More

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http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.1
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http://dx.doi.org/10.1167/iovs.18-25698DOI Listing
April 2019
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Local adaptation in natural European host grass populations with asymmetric symbiosis.

PLoS One 2019 17;14(4):e0215510. Epub 2019 Apr 17.

Natural Resources Institute Finland (Luke), Turku, Finland.

Recent work on microbiomes is revealing the wealth and importance of plant-microbe interactions. Microbial symbionts are proposed to have profound effects on fitness of their host plants and vice versa, especially when their fitness is tightly linked. Here we studied local adaptation of host plants and possible fitness contribution of such symbiosis in the context of abiotic environmental factors. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215510PLOS
April 2019
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RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation.

PLoS One 2019 17;14(4):e0214764. Epub 2019 Apr 17.

Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

Healthy mitochondria use an electrochemical gradient across the inner mitochondrial membrane (IMM) to generate energy in the form of ATP. A variety of endogenous and exogenous factors can lead to transient or sustained depolarization of the IMM, including mitochondrial fission events, expression of uncoupling proteins, electron transport chain (ETC) inhibitors, or chemical uncouplers. This depolarization in turn leads to a variety of physiological responses, ranging from selective mitochondrial clearance (mitophagy) to cell death. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214764PLOS

Evolutionary history of burrowing asps (Lamprophiidae: Atractaspidinae) with emphasis on fang evolution and prey selection.

PLoS One 2019 17;14(4):e0214889. Epub 2019 Apr 17.

Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, United States of America.

Atractaspidines are poorly studied, fossorial snakes that are found throughout Africa and western Asia, including the Middle East. We employed concatenated gene-tree analyses and divergence dating approaches to investigate evolutionary relationships and biogeographic patterns of atractaspidines with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1). We sampled 91 individuals from both atractaspidine genera (Atractaspis and Homoroselaps). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214889PLOS
April 2019
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The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs.

PLoS One 2019 17;14(4):e0214793. Epub 2019 Apr 17.

Department of Development and Regeneration, Division Organ Systems, KU Leuven, Leuven, Belgium.

Background: Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs.

Objective: We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214793PLOS
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