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Found 37684 matches. Displaying 5221-5230
Xie ZY, Zhang D, Chung DJ, Tang ZY, Huang H, Dai LZ, Qi SK, Li JY, Colak G, Chen Y, Xia CM, Peng C, Ruan HB, Kirkey M, Wang DL, Jensen LM, Kwon OK, Lee SY, Pletcher SD, Tan MJ, Lombard DB, White KP, Zhao HY, Li J, Roeder RG, Yang XY, Zhao YM
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Metabolic Regulation of Gene Expression by Histone Lysine beta-Hydroxybutyrylation
MOLECULAR CELL 2016 APR 21; 62(2):194-206
Here we report the identification and verification of a beta-hydroxybutyrate-derived protein modification, lysine beta-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated beta-hydroxybutyrate levels in cultured cells and in livers from mice subjected to prolonged fasting or streptozotocin-induced diabetic ketoacidosis. In total, we identified 44 histone Kbhb sites, a figure comparable to the known number of histone acetylation sites. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbhb is a mark enriched in active gene promoters and that the increased H3K9bhb levels that occur during starvation are associated with genes upregulated in starvation-responsive metabolic pathways. Histone beta-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and diverse functions of beta-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.
Birsoy K, Sabatini DM
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A Different Way of Doing Things
SCIENTIST 2016 APR; 30(4):47-51
Soteriou D, Kostic L, Sedov E, Yosefzon Y, Steller H, Fuchs Y
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Isolating Hair Follicle Stem Cells and Epidermal Keratinocytes from Dorsal Mouse Skin
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS 2016 APR; ?(110):? Article e53931
The hair follicle (HF) is an ideal system for studying the biology and regulation of adult stem cells (SCs). This dynamic mini organ is replenished by distinct pools of SCs, which are located in the permanent portion of the HF, a region known as the bulge. These multipotent bulge SCs were initially identified as slow cycling label retaining cells; however, their isolation has been made feasible after identification of specific cell markers, such as CD34 and keratin 15 (K15). Here, we describe a robust method for isolating bulge SCs and epidermal keratinocytes from mouse HFs utilizing fluorescence activated cell-sorting (FACS) technology. Isolated hair follicle SCs (HFSCs) can be utilized in various in vivo grafting models and are a valuable in vitro model for studying the mechanisms that govern multipotency, quiescence and activation.
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Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Taylor D, Verwilligen P, Vuosalo C, Woods N
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Search for new phenomena in monophoton final states in proton-proton collisions at root s=8 TeV
PHYSICS LETTERS B 2016 APR 10; 755(?):102-124
Results are presented from a search for new physics in final states containing a photon and missing transverse momentum. The data correspond to an integrated luminosity of 19.6 fb(-1) collected in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC. Nodeviation from the standard model predictions is observed for these final states. New, improved limits are set on dark matter production and on parameters of models with large extra dimensions. In particular, the first limits from the LHC on branon production are found and significantly extend previous limits from LEP and the Tevatron. An upper limit of 14.0 fb on the cross section is set at the 95% confidence level for events with a monophoton final state with photon transverse momentum greater than 145 GeV and missing transverse momentum greater than 140 GeV. (C) 2016 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.
Jia MX, Lu H, Markowitz M, Cheng-Mayer C, Wu XL
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Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIVSF162P3N-Infected Macaques
JOURNAL OF VIROLOGY 2016 APR; 90(8):4017-4031
To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIVSF162P3N and 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120-directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs. IMPORTANCE HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIVSF162P3N-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare, but their development might have been faster in some of the studied macaques. Plasma mapping with monomeric gp120 indicated that most bnAbs bind to the envelope trimer rather than the gp120 monomer. In support of this, none of the isolated gp120-reactive monoclonal antibodies (MAbs) displayed the neutralization breadth observed in the corresponding plasma. However, the MAb sequences revealed similarity between human and macaque genes used to encode some V3-directed MAbs. Our study sheds light on the timing and development of bnAbs in SHIV-infected macaques in comparison to HIV-1-infected humans and highlights the use of envelope trimer probes for efficient recovery of bnAbs.
Jabot-Hanin F, Cobat A, Feinberg J, Grange G, Remus N, Poirier C, Boland-Auge A, Besse C, Bustamante J, Boisson-Dupuis S, Casanova JL, Schurr E, Alcais A, Hoal EG, Delacourt C, Abel L
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Major Loci on Chromosomes 8q and 3q Control Interferon gamma Production Triggered by Bacillus Calmette-Guerin and 6-kDa Early Secretory Antigen Target, Respectively, in Various Populations
JOURNAL OF INFECTIOUS DISEASES 2016 APR 1; 213(7):1173-1179
Background. Interferon gamma (IFN-gamma) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown. Methods. We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified. Results. We identified a major locus on chromosome 8q controlling IFN-gamma production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 x 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-gamma levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-gamma production shared with that induced by BCG (LOD score, 3.72; P = 1.8 x 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. These loci differ from those previously identified as controlling the response to the tuberculin skin test (TST1 and TST2) and the production of TNF-alpha (TNF1). Conclusions. The identification of 2 new linkage signals in populations of various ethnic origins living in different M. tuberculosis exposure settings provides new clues about the genetic control of human antimycobacterial immunity.
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Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Sheldon P, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Gomber B, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Comparison of the Z/gamma* + jets to gamma + jets cross sections in pp collisions at root s = 8 (vol 10, 128, 2015)
JOURNAL OF HIGH ENERGY PHYSICS 2016 APR 4; ?(4):? Article 010
Balbontin R, Villagra N, de la Gandara MP, Mora G, Figueroa-Bossi N, Bossi L
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Expression of IroN, the salmochelin siderophore receptor, requires mRNA activation by RyhB small RNA homologues
MOLECULAR MICROBIOLOGY 2016 APR; 100(1):139-155
The iroN gene of Salmonella enterica and uropathogenic Escherichia coli encodes the outer membrane receptor of Fe3+-bound salmochelin, a siderophore tailored to evade capture by the host's immune system. The iroN gene is under negative control of the Fur repressor and transcribed under iron limiting conditions. We show here that transcriptional de-repression is not sufficient to allow iroN expression, as this also requires activation by either of two partially homologous small RNAs (sRNAs), RyhB1 and RyhB2. The two sRNAs target the same sequence segment approximately in the middle of the 94-nucleotide 5 untranslated region (UTR) of iroN mRNA. Several lines of evidence suggest that base pair interaction stimulates iroN mRNA translation. Activation does not result from the disruption of a secondary structure masking the ribosome binding site; rather it involves sequences at the 5 end of iroN 5 UTR. In vitro toeprint' assays revealed that this upstream site binds the 30S ribosomal subunit provided that RyhB1 is paired with the mRNA. Altogether, our data suggest that RyhB1, and to lesser extent RyhB2, activate iroN mRNA translation by promoting entry of the ribosome at an upstream standby' site. These findings add yet an additional nuance to the polychromatic landscape of sRNA-mediated regulation.
Lee AJ, Moncada-Velez M, Picard C, Llanora G, Huang CH, Abel L, Chan SM, Lee BW, Casanova JL, Bustamante J, Shek LPC, Boisson-Dupuis S
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Severe Mycobacterial Diseases in a Patient with GOF I kappa B alpha Mutation Without EDA (vol 36, pg 12, 2016)
JOURNAL OF CLINICAL IMMUNOLOGY 2016 APR; 36(3):335-335
Loschko J, Schreiber HA, Rieke GJ, Esterhazy D, Meredith MM, Pedicord VA, Yao KH, Caballero S, Pamer EG, Mucida D, Nussenzweig MC
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Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation
JOURNAL OF EXPERIMENTAL MEDICINE 2016 APR 4; 213(4):517-534
Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHC II) mouse. Absence of MHC II on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria.