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https://www.readbyqxmd.com/read/28643795/the-genomic-landscape-of-tuberous-sclerosis-complex
#1
Katie R Martin, Wanding Zhou, Megan J Bowman, Juliann Shih, Kit Sing Au, Kristin E Dittenhafer-Reed, Kellie A Sisson, Julie Koeman, Daniel J Weisenberger, Sandra L Cottingham, Steven T DeRoos, Orrin Devinsky, Mary E Winn, Andrew D Cherniack, Hui Shen, Hope Northrup, Darcy A Krueger, Jeffrey P MacKeigan
Tuberous sclerosis complex (TSC) is a rare genetic disease causing multisystem growth of benign tumours and other hamartomatous lesions, which leads to diverse and debilitating clinical symptoms. Patients are born with TSC1 or TSC2 mutations, and somatic inactivation of wild-type alleles drives MTOR activation; however, second hits to TSC1/TSC2 are not always observed. Here, we present the genomic landscape of TSC hamartomas. We determine that TSC lesions contain a low somatic mutational burden relative to carcinomas, a subset feature large-scale chromosomal aberrations, and highly conserved molecular signatures for each type exist...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643204/host-factors-in-coronavirus-replication
#2
Adriaan H de Wilde, Eric J Snijder, Marjolein Kikkert, Martijn J van Hemert
Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviruses, our options to prevent or treat coronavirus infections remain very limited...
June 23, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28643086/gallic-and-ellagic-acids-two-natural-immunomodulator-compounds-solve-infection-of-macrophages-by-leishmania-major
#3
Michel Muálem de Moraes Alves, Lucas Moreira Brito, Adriana Cunha Souza, Bárbara Cristina Silva Holanda Queiroz, Thaynara Parente de Carvalho, Joilson Ferreira Batista, Jéssica Sara de Sousa Macêdo Oliveira, Ivete Lopes de Mendonça, Silvéria Regina de Sousa Lira, Mariana Helena Chaves, Juan Carlos Ramos Gonçalves, Sabrina Maria Portela Carneiro, Daniel Dias Rufino Arcanjo, Fernando Aécio de Amorim Carvalho
Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities...
June 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28642887/dynamic-regulation-of-serum-aryl-hydrocarbon-receptor-agonists-in-ms
#4
Veit Rothhammer, Davis M Borucki, Maria Isabel Garcia Sanchez, Maria Antonietta Mazzola, Christopher C Hemond, Keren Regev, Anu Paul, Pia Kivisäkk, Rohit Bakshi, Guillermo Izquierdo, Howard L Weiner, Francisco J Quintana
OBJECTIVE: Several factors influence the clinical course of autoimmune inflammatory diseases such as MS and inflammatory bowel disease. Only recently, the complex interaction between the gut microbiome, dietary factors, and metabolism has started to be appreciated with regard to its potential to modulate acute and chronic inflammation. One of the molecular sensors that mediates the effects of these environmental signals on the immune response is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with key functions in immune cells...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28642760/interleukin-6-in-allogeneic-stem-cell-transplantation-its-possible-importance-for-immunoregulation-and-as-a-therapeutic-target
#5
REVIEW
Tor Henrik Anderson Tvedt, Elisabeth Ersvaer, Anders Aune Tveita, Øystein Bruserud
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28641579/lps-alters-the-immuno-phenotype-of-glioma-and-glioma-stem-like-cells-and-induces-in-vivo-antitumor-immunity-via-tlr4
#6
Sheng Han, Chao Wang, Xiaofei Qin, Junzhe Xia, Anhua Wu
BACKGROUND: This study examined the ability of lipopolysaccharide (LPS) to affect glioma and glioma stem-like cells (GSCs) in vitro and to induce antitumor immunity in vivo and the role of TLR4 in these processes. METHODS: Using RT-PCR and immunohistochemistry, we examined the expression of TLR4 in 34 glioblastoma clinical samples. Using real time-PCR, western blot and ELISA analyses, the effect of LPS stimulation on the expression of immune related molecules was evaluated in RG2 and U87 GSCs...
June 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28641569/a-review-on-defects-of-dendritic-cells-in-common-variable-immunodeficiency
#7
Laleh Sharifi, Naeimeh Tavakolinia, Fatemeh Kiaee, Nima Rezaie, Monireh Mohsenzadegan, Mansoureh Shariat, Reza Yazdani, Abbas Mirshafiey, Asghar Aghamohammadi, Gholamreza Azizi
BACKGROUND AND OBJECTIVES: Common variable immunodeficiency (CVID) is the most important primary that is associated with clinical complications including recurrent infections, malignancy and autoimmune diseases. The genetic cause of CVID is mostly unknown and only a few genetic causes are identified. The various options are proposed for determining the etiology of CVID patients, such as T- and B-cell defects, Toll-like receptors (TLRs) impairments, altered cytokine production as well as blemished dendritic cells (DCs)...
June 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28640898/competition-between-influenza-a-virus-subtypes-through-heterosubtypic-immunity-modulates-re-infection-and-antibody-dynamics-in-the-mallard-duck
#8
Neus Latorre-Margalef, Justin D Brown, Alinde Fojtik, Rebecca L Poulson, Deborah Carter, Monique Franca, David E Stallknecht
Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640534/dynamics-of-transcriptomic-response-to-infection-by-the-nematode-heterorhabditis-bacteriophora-and-its-bacterial-symbiont-photorhabdus-temperata-in-heliothis-virescens-larvae
#9
R An, K S Suri, J L Jurat-Fuentes, P S Grewal
Entomopathogenic nematodes in the Heterorhabditis genus and their symbiotic Photorhabdus bacteria are important biocontrol agents of insect pests and models for the study of microbe-host interactions. In this work, we used larvae of the tobacco budworm (Heliothis virescens) as a model to study its defensive mechanisms against Heterorhabditis bacteriophora nematodes carrying symbiotic Photorhabdus temperata. We first determined time points of initial nematode entry and release of bacteria into the haemolymph to perform transcriptional analysis of insect gene expression during these steps in the infective process...
June 22, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28640444/impact-of-growth-hormone-on-regulation-of-adipose-tissue
#10
Katie M Troike, Brooke E Henry, Elizabeth A Jensen, Jonathan A Young, Edward O List, John J Kopchick, Darlene E Berryman
Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#11
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638602/b-cell-depleting-therapy-with-rituximab-or-ofatumumab-in-immunoglobulin-a-nephropathy-or-vasculitis-with-nephritis
#12
Sigrid Lundberg, Emelie Westergren, Jessica Smolander, Annette Bruchfeld
BACKGROUND: Approximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic-nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28638345/heterogeneity-and-developmental-connections-between-cell-types-inhabiting-teeth
#13
REVIEW
Jan Krivanek, Igor Adameyko, Kaj Fried
Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix-producing populations: ameloblasts generating enamel and odontoblasts producing dentin...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28637844/a-dirty-cause-of-vancomycin-mediated-henoch-schonlein-purpura-oxygen-tubing-is-not-a-foley
#14
Nikhil H Shah, Kristopher P Kline, Manas K Shukla
A 59-year-old male presented with methicillin-resistantStaphylococcus aureus bacteraemia from a prostatic abscess and was treated with vancomycin. Two weeks into his treatment course, he developed severe joint pains, abdominal pain with bloody, mucinous stools and a diffuse palpable purpuric rash on his extremities. Biopsy of the rash showed IgA immune-complex deposition consistent with Henoch-Schönlein purpura. After treatment with glucocorticoids, his symptoms resolved completely. Vancomycin is an extremely commonly used antibiotic with certain well-known adverse effects...
June 20, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28637753/structural-mimicry-of-the-dengue-virus-envelope-glycoprotein-revealed-by-the-crystallographic-study-of-an-idiotype-anti-idiotype-fab-complex
#15
Yee Hwa Wong, Boon Chong Goh, She Yah Lim, En Wei Teo, Angeline P C Lim, Pete C Dedon, Brendon J Hanson, Paul A MacAry, Julien Lescar
A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic Flaviviruses such as Dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope- a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637738/the-reanimation-low-immune-status-markers-realism-project-a-protocol-for-broad-characterisation-and-follow-up-of-injury-induced-immunosuppression-in-intensive-care-unit-icu-critically-ill-patients
#16
Mary-Luz Rol, Fabienne Venet, Thomas Rimmele, Virginie Moucadel, Pierre Cortez, Laurence Quemeneur, David Gardiner, Andrew Griffiths, Alexandre Pachot, Julien Textoris, Guillaume Monneret
INTRODUCTION: The host response to septic shock is dynamic and complex. A sepsis-induced immunosuppression phase has recently been acknowledged and linked to bad outcomes and increased healthcare costs. Moreover, a marked suppression of the immune response has also been partially described in patients hospitalized in intensive care unit (ICU) for severe trauma or burns. It has been hypothesized that immune monitoring could enable identification of patients who might most benefit from novel, adjunctive immune-stimulating therapies...
June 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28637589/elevated-factor-h-related-protein-1-and-factor-h-pathogenic-variants-decrease-complement-regulation-in%C3%A2-iga-nephropathy
#17
Agustín Tortajada, Eduardo Gutiérrez, Elena Goicoechea de Jorge, Jaouad Anter, Alfons Segarra, Mario Espinosa, Miquel Blasco, Elena Roman, Helena Marco, Luis F Quintana, Josué Gutiérrez, Sheila Pinto, Margarita Lopez-Trascasa, Manuel Praga, Santiago Rodriguez de Córdoba
IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (ΔCFHR3-CFHR1). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals...
June 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#18
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28637300/commercial-rodent-diets-differentially-regulate-autoimmune-glomerulonephritis-epigenetics-and-microbiota-in-mrl-lpr-mice
#19
Michael R Edwards, Rujuan Dai, Bettina Heid, Thomas E Cecere, Deena Khan, Qinghui Mu, Catharine Cowan, Xin M Luo, S Ansar Ahmed
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone rich soy and alfalfa, Harlan 2018 isoflavone rich soy-based diet, or ResearchDiets Inc...
June 15, 2017: International Immunology
https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#20
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
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