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https://www.readbyqxmd.com/read/27923061/comparative-transcriptomic-and-epigenomic-analyses-reveal-new-regulators-of-murine-brown-adipogenesis
#1
Reinhard Brunmeir, Jingyi Wu, Xu Peng, Sun-Yee Kim, Sofi G Julien, Qiongyi Zhang, Wei Xie, Feng Xu
Increasing energy expenditure through brown adipocyte recruitment is a promising approach to combat obesity. We report here the comprehensive profiling of the epigenome and transcriptome throughout the lineage commitment and differentiation of C3H10T1/2 mesenchymal stem cell line into brown adipocytes. Through direct comparison to datasets from differentiating white adipocytes, we systematically identify stage- and lineage-specific coding genes, lncRNAs and microRNAs. Utilizing chromatin state maps, we also define stage- and lineage-specific enhancers, including super-enhancers, and their associated transcription factor binding motifs and genes...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27917284/the-neurobiology-of-dispositional-negativity-and-attentional-biases-to-threat-implications-for-understanding-anxiety-disorders-in-adults-and-youth
#2
Alexander J Shackman, Melissa D Stockbridge, Rachael M Tillman, Claire M Kaplan, Do P M Tromp, Andrew S Fox, Matthias Gamer
When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun to come into focus. Here we review recent work highlighting the importance of neural circuits centered on the amygdala. We begin by describing dispositional negativity, a core dimension of childhood temperament and adult personality and an important risk factor for the development of anxiety disorders and other kinds of stress-sensitive psychopathology...
2016: Journal of Experimental Psychopathology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#3
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910764/metabolic-regulation-of-natural-killer-cell-ifn-%C3%AE-production
#4
Annelise Y Mah, Megan A Cooper
Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27906775/improving-liver-allocation-using-optimized-neighborhoods
#5
Vikram Kilambi, Sanjay Mehrotra
BACKGROUND: Geographic disparities persist in access to liver transplantation. Candidates with similar urgency experience varying opportunities for transplants across the US. Policymakers are poised to act and 1 proposal entails reorganizing the current OPTN of 11 regions into 8 districts. However, redistricting has the shortcomings that OPOs are disconnected from their immediate neighbors by district borders and that it is not easily responsive to uncertainty resulting from variability in donor and listing rates...
October 7, 2016: Transplantation
https://www.readbyqxmd.com/read/27906472/long-term-clinical-impact-and-cost-effectiveness-of-obeticholic-acid-for-the-treatment-of-primary-biliary-cholangitis
#6
Sumeyye Samur, Matthew Klebanoff, Reiner Banken, Daniel S Pratt, Rick Chapman, Daniel A Ollendorf, Anne M Loos, Kathleen Corey, Chin Hur, Jagpreet Chhatwal
: Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA...
November 7, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#7
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902405/microbial-nanowires-an-electrifying-tale
#8
Sandeep K Sure, Leigh M Ackland, Angel A Torriero, Alok Adholeya, Mandira Kochar
Electromicrobiology has gained momentum in the last ten years with advances in microbial fuel cells and the discovery of microbial nanowires (MNWs). The list of MNWs producing microorganisms is growing and providing intriguing insights into the presence of such microorganisms in diverse environments and the potential roles MNWs can perform. This review discusses the MNWs produced by different microorganisms, including their structure, composition and role in electron transfer through MNWs. Two hypotheses, metallic-like conductivity and an electron hopping model, have been proposed for electron transfer and we present a current understanding of both these hypotheses...
October 21, 2016: Microbiology
https://www.readbyqxmd.com/read/27900765/the-role-of-the-otolaryngologist-in-the-evaluation-and-diagnosis-of-eosinophilic-esophagitis
#9
Mark Kubik, Prasad Thottam, Amber Shaffer, Sukgi Choi
OBJECTIVE: To describe the clinical presentation and role of the otolaryngologist in the evaluation of eosinophilic esophagitis (EoE) at a tertiary pediatric hospital. STUDY DESIGN: Retrospective review. METHODS: Records from pediatric patients with a diagnosis of EoE from 2003 to 2015 were reviewed. Study variables were analyzed to compare patients presenting to different specialties. RESULTS: Two hundred and fifty-one patients with EoE were evaluated...
November 30, 2016: Laryngoscope
https://www.readbyqxmd.com/read/27898391/replication-fork-instability-and-the-consequences-of-fork-collisions-from-rereplication
#10
REVIEW
Jessica L Alexander, Terry L Orr-Weaver
Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27895110/nucleosome-occupancy-as-a-novel-chromatin-parameter-for-replication-origin-functions
#11
Jairo Rodriguez, Laura Lee, Bryony Lynch, Toshio Tsukiyama
Eukaryotic DNA replication initiates from multiple discrete sites in the genome termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have showed that chromatin can strongly influence initiation of DNA replication...
November 28, 2016: Genome Research
https://www.readbyqxmd.com/read/27893742/maintenance-of-taste-organs-is-strictly-dependent-on-epithelial-hedgehog-gli-signaling
#12
Alexandre N Ermilov, Archana Kumari, Libo Li, Ariell M Joiner, Marina A Grachtchouk, Benjamin L Allen, Andrzej A Dlugosz, Charlotte M Mistretta
For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27892478/continuous-single-cell-imaging-reveals-sequential-steps-of-plasmacytoid-dendritic-cell-development-from-common-dendritic-cell-progenitors
#13
Ezgi Dursun, Max Endele, Andrea Musumeci, Henrik Failmezger, Shu-Hung Wang, Achim Tresch, Timm Schroeder, Anne B Krug
Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c(+) MHCII(-) precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892454/miniature-optical-planar-camera-based-on-a-wide-angle-metasurface-doublet-corrected-for-monochromatic-aberrations
#14
Amir Arbabi, Ehsan Arbabi, Seyedeh Mahsa Kamali, Yu Horie, Seunghoon Han, Andrei Faraon
Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify optical wavefronts at subwavelength spatial resolution. They are poised to revolutionize optics by enabling complex low-cost systems where multiple metasurfaces are lithographically stacked and integrated with electronics. For imaging applications, metasurface stacks can perform sophisticated image corrections and can be directly integrated with image sensors. Here we demonstrate this concept with a miniature flat camera integrating a monolithic metasurface lens doublet corrected for monochromatic aberrations, and an image sensor...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27886537/bioelectrochemical-approach-for-reductive-and-oxidative-dechlorination-of-chlorinated-aliphatic-hydrocarbons-cahs
#15
Agnese Lai, Federico Aulenta, Marina Mingazzini, Maria Teresa Palumbo, Marco Petrangeli Papini, Roberta Verdini, Mauro Majone
A sequential reductive-oxidative treatment was developed in this study in a continuous-flow bioelectrochemical reactor to address bioremediation of groundwater contaminated by trichloroethene (TCE) and less-chlorinated but still harmful intermediates, such as vinyl chloride. In order to optimize the anodic compartment, whereby the oxygen-driven microbial oxidation of TCE-daughter products occurs, abiotic batch experiments were performed with various anode materials poised at +1.20 V vs. SHE (i.e., graphite rods and titanium mesh anode coated with mixed metal oxides (MMO)) and setups (i...
November 22, 2016: Chemosphere
https://www.readbyqxmd.com/read/27885887/cell-therapies-for-parkinson-s-disease-how-far-have-we-come
#16
Thomas B Stoker, Roger A Barker
Over the past three decades, significant progress has been made in the development of potential regenerative cell-based therapies for neurodegenerative disease, with most success being seen in Parkinson's disease. Cell-based therapies face many challenges including ethical considerations, potential for immune-mediated rejection with allogeneic and xenogeneic tissue, pathological spread of protein-related disease into the grafted tissue as well as the risk of graft overgrowth and tumorigenesis in stem cell-derived transplants...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27884598/coiled-coils-a-model-system-for-the-21st-century
#17
REVIEW
Andrei N Lupas, Jens Bassler
α-Helical coiled coils were described more than 60 years ago as simple, repetitive structures mediating oligomerization and mechanical stability. Over the past 20 years, however, they have emerged as one of the most diverse protein folds in nature, enabling many biological functions beyond mechanical rigidity, such as membrane fusion, signal transduction, and solute transport. Despite this great diversity, their structures can be described by parametric equations, making them uniquely suited for rational protein design...
November 21, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27883012/immune-signatures-of-protective-spleen-memory-cd8-t-cells
#18
Lilia Brinza, Sophia Djebali, Martine Tomkowiak, Julien Mafille, Céline Loiseau, Pierre-Emmanuel Jouve, Simon de Bernard, Laurent Buffat, Bruno Lina, Michèle Ottmann, Manuel Rosa-Calatrava, Stéphane Schicklin, Nathalie Bonnefoy, Grégoire Lauvau, Morgan Grau, Mélanie Wencker, Christophe Arpin, Thierry Walzer, Yann Leverrier, Jacqueline Marvel
Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876760/changes-of-bivalent-chromatin-coincide-with-increased-expression-of-developmental-genes-in-cancer
#19
Stephan H Bernhart, Helene Kretzmer, Lesca M Holdt, Frank Jühling, Ole Ammerpohl, Anke K Bergmann, Bernd H Northoff, Gero Doose, Reiner Siebert, Peter F Stadler, Steve Hoffmann
Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872212/a-proinflammatory-role-of-type-2-innate-lymphoid-cells-in-murine-immune-mediated-hepatitis
#20
Katrin Neumann, Khalil Karimi, Jana Meiners, Ruth Voetlause, Silja Steinmann, Werner Dammermann, Stefan Lüth, Farahnaz Asghari, Claudia Wegscheid, Andrea K Horst, Gisa Tiegs
Type 2 innate lymphoid cells (ILC2) mediate inflammatory immune responses in the context of diseases triggered by the alarmin IL-33. In recent years, IL-33 has been implicated in the pathogenesis of immune-mediated liver diseases. However, the immunoregulatory function of ILC2s in the inflamed liver remains elusive. Using the murine model of Con A-induced immune-mediated hepatitis, we showed that selective expansion of ILC2s in the liver was associated with highly elevated hepatic IL-33 expression, severe liver inflammation, and infiltration of eosinophils...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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