- Research ArticleDynamic stroma reorganization drives blood vessel dysmorphia during glioma growth
- Thomas Mathivet (thomas.mathivet{at}inserm.fr)*,1,2,
- Claire Bouleti1,2,
- Matthias Van Woensel3,
- Fabio Stanchi1,2,
- Tina Verschuere3,
- Li‐Kun Phng1,2,4,
- Joost Dejaegher3,
- Marly Balcer1,2,
- Ken Matsumoto1,2,
- Petya B Georgieva1,2,
- Jochen Belmans3,
- Raf Sciot5,
- Christian Stockmann6,
- Massimiliano Mazzone7,8,
- Steven De Vleeschouwer3,9 and
- Holger Gerhardt (holger.gerhardt{at}kuleuven.vib.be)*,1,2,10,11
- 1Vascular Patterning Lab, Center for Cancer Biology, VIB, Leuven, Belgium
- 2Vascular Patterning Lab, Department of Oncology, KU Leuven, Leuven, Belgium
- 3Department of Neurosciences, Laboratory of Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium
- 4Laboratory for Vascular Morphogenesis, RIKEN Center for Developmental Biology, Kobe, Japan
- 5Department of Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium
- 6UMR 970, Paris Cardiovascular Research Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
- 7Lab of Molecular Oncology and Angiogenesis, Department of Oncology, KU Leuven, Leuven, Belgium
- 8Lab of Molecular Oncology and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium
- 9Department of Neurosciences, KU Leuven, Leuven, Belgium
- 10Integrative Vascular Biology Laboratory, Max‐Delbrück‐Center for Molecular Medicine, Helmholtz Association (MDC), Berlin, Germany
- 11Berlin Institute of Health (BIH), Berlin, Germany
- ↵*
Corresponding author. Tel: +33 153988018; E‐mail: thomas.mathivet{at}inserm.fr
Corresponding author. Tel: +32 16373220; E‐mail: holger.gerhardt{at}kuleuven.vib.be
Dynamic multi‐photon imaging and genetic labeling and targeting in an orthotopic tumor model reveals that progressive changes in stromal cells are the leading cause of vascular dysmorphia in glioma.
Synopsis
Dynamic multi‐photon imaging and genetic labeling and targeting in an orthotopic tumor model reveals that progressive changes in stromal cells are the leading cause of vascular dysmorphia in glioma.
Initial tumour growth is accompanied by functional vessel patterning.
Progressive blood vessel dysmorphia coincides with bone‐marrow derived macrophage recruitment.
M2‐polarized macrophages accumulate around tumour blood vessels in glioma progression in mouse and with increasing WHO grades in humans.
Depleting macrophages or their VEGF production restore blood vessel caliber and function.
Macrophages depletion enhances efficacy of chemotherapeutic agents.
- Received December 8, 2016.
- Revision received September 12, 2017.
- Accepted September 13, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- CommentaryDefamation lawsuits: academic sword or shield?
Scientists and academics are used to defending their theories, methods, and results in the classroom, at conferences, and in peer‐reviewed publications. But Pieter Cohen, an assistant professor at Harvard Medical School, learned that he had to defend his research in a defamation suit while reading a supplement industry trade publication (Robins, 2017). Cohen is known as a “dogged detective” for scrutinizing dietary supplements and for advocating for their stricter oversight by the US Food and Drug Administration (FDA).
Libel lawsuits have been abused in the USA and UK to cow scientists and publishers into silence. Although peer review provides some protection and both countries have addressed libel abuse, it can still impact on free speech and exchange of ideas in academia.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Research ArticleHousehold triclosan and triclocarban effects on the infant and maternal microbiome
- Jessica V Ribado1,
- Catherine Ley2,
- Thomas D Haggerty2,
- Ekaterina Tkachenko3,
- Ami S Bhatt (asbhatt{at}stanford.edu)*,1,3 and
- Julie Parsonnet (parsonnt{at}stanford.edu)*,2,4
- 1Department of Genetics, Stanford University, Stanford, CA, USA
- 2Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA
- 3Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA
- 4Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, CA, USA
- ↵*
Corresponding author. Tel: +1 650 498 4438; E‐mail: asbhatt{at}stanford.edu
Corresponding author. Tel: +1 650 725 4561; E‐mail: parsonnt{at}stanford.edu
The extent to which exposure to common household antimicrobials, mainly triclosan and triclocarban (referred to as TCs), disrupts human adult and developing infant microbiomes was unknown. This study reveals an effect on mothers through oral rather than skin exposure.
Synopsis
The extent to which exposure to common household antimicrobials, mainly triclosan and triclocarban (referred to as TCs), disrupts human adult and developing infant microbiomes was unknown. This study reveals an effect on mothers through oral rather than skin exposure.
Microbiome diversity is not affected in adults or infants by household TC exposure.
Mothers of TC households show an enrichment of phylum known to harbor and associate with wide antibiotic resistance, only after the introduction of oral care products containing triclosan.
Selection of gut microbes by TC may be driven by oral exposure more than skin exposure.
- Received April 10, 2017.
- Revision received September 5, 2017.
- Accepted September 11, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Research ArticleDisease‐modifying effects of ganglioside GM1 in Huntington's disease models
- Melanie Alpaugh1,2,
- Danny Galleguillos1,2,
- Juan Forero2,3,
- Luis Carlos Morales1,
- Sebastian W Lackey1,
- Preeti Kar1,
- Alba Di Pardo1,6,
- Andrew Holt1,
- Bradley J Kerr2,4,
- Kathryn G Todd2,5,
- Glen B Baker2,5,
- Karim Fouad2,3 and
- Simonetta Sipione (ssipione{at}ualberta.ca)*,1,2
- 1Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
- 2Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
- 3Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, AB, Canada
- 4Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB, Canada
- 5Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
- 6Present Address: Center for Neurogenetics and Rare Diseases, IRCCS Neuromed, Pozzilli, Italy
- ↵*Corresponding author. Tel: +1 780 492 5885; E‐mail: ssipione{at}ualberta.ca
Huntington's disease (HD) is an incurable neurodegenerative disease. Intraventricular administration of ganglioside GM1 in three different HD mouse models ameliorates huntingtin levels, brain and striatal atrophy, motor and cognitive defects and other neurochemical levels.
Synopsis
Huntington's disease (HD) is an incurable neurodegenerative disease. Intraventricular administration of ganglioside GM1 in three different HD mouse models ameliorates huntingtin levels, brain and striatal atrophy, motor and cognitive defects and other neurochemical levels.
Administration of GM1 decreases levels of toxic soluble and insoluble mutant huntingtin.
GM1 slows down neurodegeneration and white matter atrophy in R6/2 mice.
GM1 restores normal levels of key neurotransmitters in the brain.
GM1 improves and even restores to normal motor function in HD mice, and corrects psychiatric‐like and cognitive dysfunction.
GM1 could be a novel disease‐modifying therapy for HD.
- Received March 1, 2017.
- Revision received September 6, 2017.
- Accepted September 8, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Research ArticleTGF‐β1 secreted by Tregs in lymph nodes promotes breast cancer malignancy via up‐regulation of IL‐17RB
- Shih‐Chia Huang1,
- Pei‐Chi Wei1,
- Wendy W Hwang‐Verslues1,
- Wen‐Hung Kuo2,
- Yung‐Ming Jeng3,
- Chun‐Mei Hu1,
- Jin‐Yuh Shew1,
- Chiun‐Sheng Huang2,
- King‐Jen Chang2,
- Eva Y‐HP Lee1,4 and
- Wen‐Hwa Lee (whlee{at}uci.edu)*,1,5
- 1Genomics Research Center, Academia Sinica, Taipei, Taiwan
- 2Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- 3Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
- 4Department of Biological Chemistry, University of California, Irvine, CA, USA
- 5Institute of New Drug Development, China Medical University, Taichung, Taiwan
- ↵*Corresponding author. Tel: +886 2 27898777; E‐mail: whlee{at}uci.edu
Treg‐secreted TGF‐β1 in the tumor‐draining LN (TDLN) microenvironment up‐regulates IL‐17RB expression in breast cancer cells, thereby enhancing their metastatic potential.
Synopsis
Treg‐secreted TGF‐β1 in the tumor‐draining LN (TDLN) microenvironment up‐regulates IL‐17RB expression in breast cancer cells, thereby enhancing their metastatic potential.
Breast cancer cells isolated from TDLN displayed aggressive phenotypes; removal of TDLN reduced distant organ metastasis.
Tregs in TDLN was the major cell type contributing to the enhanced malignancy of breast cancer cells.
TGF‐β1 secreted from Tregs in TDLN up‐regulated IL‐17RB expression in breast cancer cells.
Up‐regulation of IL‐17RB by TGF‐β1 occurred through Smad2/3/4 signal pathway.
- Received August 4, 2016.
- Revision received September 8, 2017.
- Accepted September 12, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ReportPeroxisome proliferator‐activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut
- Mathurin Fumery1,2,3,†,
- Silvia Speca1,2,†,
- Audrey Langlois1,2,
- Anne‐Marie Davila4,
- Caroline Dubuquoy5,
- Marta Grauso4,
- Anthony Martin Mena1,2,
- Martin Figeac6,
- Daniel Metzger7,
- Christel Rousseaux5,
- Jean‐Frederic Colombel8,
- Laurent Dubuquoy1,2,
- Pierre Desreumaux1,2,9 and
- Benjamin Bertin (benjamin.bertin-2{at}univ-lille2.fr)*,1,2
- 1U995—LIRIC—Lille Inflammation Research International Center, Univ. Lille, Lille, France
- 2Inserm, U995, Lille, France
- 3Service d'Hépatogastroentérologie, Centre Hospitalier Universitaire d'Amiens Université de Picardie Jules Verne, Amiens, France
- 4UMR0914, Institut National de la Recherche Agronomique/AgroParisTech, Université Paris‐Saclay, Paris, France
- 5Intestinal Biotech Development, Lille, France
- 6Functional and Structural Genomic Platform, Université de Lille, Lille, France
- 7Institut de Génétique et de Biologie Moléculaire et Cellulaire CNRS, UMR7104/INSERM U964/Université de Strasbourg Collège de France, Paris, France
- 8The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- 9CHU Lille, Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Claude Huriez, Lille, France
- ↵*Corresponding author. Tel: +33 3 2062 7738; E‐mail: benjamin.bertin-2{at}univ-lille2.fr
↵† These authors contributed equally to this work
The activation of the nuclear receptor Peroxisome Proliferator‐Activated Receptor gamma (PPARγ) increases the expression and activity of the lactase (LCT) enzyme and improves the biological disturbances induced by a lactose‐enriched diet in rodents.
Synopsis
The activation of the nuclear receptor Peroxisome Proliferator‐Activated Receptor gamma (PPARγ) increases the expression and activity of the lactase (LCT) enzyme and improves the biological disturbances induced by a lactose‐enriched diet in rodents.
Synthetic and natural PPARγ agonist ligands are able to increase the expression and activity of LCT in Caco‐2 cells as well as in the proximal small intestine of mice and rats.
Weaned rats fed with a lactose‐enriched diet developed diarrhea associated with an increased fermentation activity of undigested lactose, which are both significantly improved by a PPARγ agonist.
Modulating intestinal PPARγ activity might improve the symptoms associated with hypolactasia and lactose malabsorption in humans.
- Received March 13, 2017.
- Revision received August 29, 2017.
- Accepted September 1, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Research ArticleProfiling MHC II immunopeptidome of blood‐stage malaria reveals that cDC1 control the functionality of parasite‐specific CD4 T cells
- Marion Draheim1,
- Myriam F Wlodarczyk1,
- Karine Crozat2,
- Jean‐Michel Saliou3,4,
- Tchilabalo Dilezitoko Alayi3,4,
- Stanislas Tomavo3,4,
- Ali Hassan1,
- Anna Salvioni1,
- Claudia Demarta‐Gatsi5,
- John Sidney6,
- Alessandro Sette6,
- Marc Dalod2,
- Antoine Berry1,
- Olivier Silvie7 and
- Nicolas Blanchard (nicolas.blanchard{at}inserm.fr)*,1
- 1Centre de Physiopathologie Toulouse Purpan (CPTP), INSERM, CNRS, Université de Toulouse, UPS, Toulouse, France
- 2CNRS, INSERM, CIML, Aix Marseille Université, Marseille, France
- 3Centre d'Infection et d'Immunité de Lille (CIIL), CNRS UMR 8204, Inserm U1019, CHU Lille, Institut Pasteur de Lille, University of Lille, Lille, France
- 4Plateforme de Protéomique et Peptides Modifiés (P3M), CNRS, Institut Pasteur de Lille, University of Lille, Lille, France
- 5CNRS, INSERM, Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, Paris, France
- 6La Jolla Institute of Allergy and Immunology, San Diego, CA, USA
- 7INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, UPMC University of Paris 06, Paris, France
- ↵*Corresponding author. Tel: +33 562 74 83 07; E‐mail: nicolas.blanchard{at}inserm.fr
To better understand how dendritic cells (DCs) control the functionality of parasite‐specific CD4 T cells and help in vaccine design, the MHC II immunopeptidome of blood stage Plasmodium berghei malaria was profiled. Type I DCs were found to promote Th1 cells and inhibit IL‐10 regulatory T cells.
Synopsis
To better understand how dendritic cells (DCs) control the functionality of parasite‐specific CD4 T cells and help in vaccine design, the MHC II immunopeptidome of blood stage Plasmodium berghei malaria was profiled. Type I DCs were found to promote Th1 cells and inhibit IL‐10 regulatory T cells.
The immunopeptidome presented by MHC II on the surface of dendritic cells during blood stage malaria is profiled by MS/MS and uncovered 14 peptides.
The three dominant CD4 responses during Plasmodium berghei ANKA infection target the ETRAMP10.2, GAPDH and EF1α antigens.
CD8α+ XCR1+ type I dendritic cells (cDC1) display higher MHC II presentation of Plasmodium‐derived antigens than type II DC (cDC2).
cDC1 are required for the differentiation of parasite‐specific IFNγ/TNF+ Th1 cells but are inhibitory for the development of IL‐10+ CD4 T cells.
- Received June 8, 2017.
- Revision received August 25, 2017.
- Accepted August 29, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
