TY - JOUR AB - The plasma membrane contributes to the formation of autophagosomes, the double-membrane vesicles that sequester cytosolic cargo and deliver it to lysosomes for degradation during autophagy. In this study, we have identified a regulatory role for connexins (Cx), the main components of plasma membrane gap junctions, in autophagosome formation. We have found that plasma-membrane-localized Cx proteins constitutively downregulate autophagy through a direct interaction with several autophagy-related proteins involved in the initial steps of autophagosome formation, such as Atg16 and components of the PI(3)K autophagy initiation complex (Vps34, Beclin-1 and Vps15). On nutrient starvation, this inhibitory effect is released by the arrival of Atg14 to the Cx-Atg complex. This promotes the internalization of Cx-Atg along with Atg9, which is also recruited to the plasma membrane in response to starvation. Maturation of the Cx-containing pre-autophagosomes into autophagosomes leads to degradation of these endogenous inhibitors, allowing for sustained activation of autophagy. AD - Department of Developmental and Molecular Biology and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York 10461, USA. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA. AN - 24705551 AU - Bejarano, E. AU - Yuste, A. AU - Patel, B. AU - Stout Jr, R. F. AU - Spray, D. C. AU - Cuervo, A. M. C1 - 7 CN - 12889 DA - Apr 6 DO - 10.1038/ncb2934 DP - Nlm ET - 2014/04/08 J2 - Nature cell biology L1 - internal-pdf://1988171360/Bejarano-2014-Connexins modulate autophagosome.pdf internal-pdf://0447289006/Bejarano-2014-Connexins modulate autophagosom1.pdf LA - Eng LB - 24705551 N1 - 1476-4679 Bejarano, Eloy Yuste, Andrea Patel, Bindi Stout Jr, Randy F Spray, David C Cuervo, Ana Maria Journal article Nat Cell Biol. 2014 Apr 6. doi: 10.1038/ncb2934. PY - 2014 RI - 2014 from pubmed SN - 1465-7392 ST - Connexins modulate autophagosome biogenesis T2 - Nat Cell Biol TI - Connexins modulate autophagosome biogenesis TT - P01 AG031782 P01 DK041918 R01 AG021904 R01 DK021860 R01 DK098408 R37 AG021904 T32 NS007439 UR - http://www.nature.com/ncb/journal/vaop/ncurrent/pdf/ncb2934.pdf ID - 7 ER - TY - JOUR AB - To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n=428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the Bonferroni threshold with Pallele<10(-8); two of these six had Pgenotype<10(-8). Quantitative trait loci mapping confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in a replication group (n=436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (Pgenotype=0.023). A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010, Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase alpha-like 1) (Pgenotype=0.042). DIAPH2 has been associated with premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates with lifespan in animal models, although not humans. KCND2 is expressed in human skin, but has not been associated with aging. These genes represent new candidate genes to study the molecular basis of healthy skin aging. AD - Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA. Albert Einstein College of Medicine, Bronx, New York, USA. Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio, USA. AN - 24037343 AU - Chang, A. L. AU - Atzmon, G. AU - Bergman, A. AU - Brugmann, S. AU - Atwood, S. X. AU - Chang, H. Y. AU - Barzilai, N. C1 - 5 C2 - PMC3923276 CN - 12899 DA - Mar DO - 10.1038/jid.2013.381 DP - Nlm ET - 2013/09/17 J2 - The Journal of investigative dermatology KW - Aged Aged, 80 and over Animals Carrier Proteins/*genetics Face Female *Genome-Wide Association Study Genotype Humans Jews/*genetics Langerhans Cells/physiology Linear Models Linkage Disequilibrium Male Membrane Proteins/*genetics Middle Aged Phenotype Polymorphism, Single Nucleotide Shal Potassium Channels/*genetics Skin Aging/*genetics L1 - internal-pdf://1558976314/Chang-2014-Identification of genes promoting s.pdf internal-pdf://1296766794/Chang-2014-Identification of genes promoting 1.pdf LA - eng LB - 24037343 M1 - 3 N1 - 1523-1747 Chang, Anne L S Atzmon, Gil Bergman, Aviv Brugmann, Samantha Atwood, Scott X Chang, Howard Y Barzilai, Nir Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States J Invest Dermatol. 2014 Mar;134(3):651-7. doi: 10.1038/jid.2013.381. Epub 2013 Sep 13. PY - 2014 RI - 2014 from pubmed SN - 0022-202x SP - 651-7 ST - Identification of genes promoting skin youthfulness by genome-wide association study T2 - J Invest Dermatol TI - Identification of genes promoting skin youthfulness by genome-wide association study TT - DK-20541 P01AG021654 P30AG038072 Howard Hughes Medical Institute UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923276/pdf/jid2013381a.pdf VL - 134 ID - 10 ER - TY - JOUR AB - Ab-secreting cell (ASC) expansion and survival are important processes in optimizing vaccines and controlling autoimmunity. The microenvironment of the medullary cords is positioned to control these key processes. Previously, we imaged and characterized ASC differentiation and migration by intravital microscopy in the lymph node (LN) by transferring and activating B cells expressing yellow fluorescent protein only in the ASC compartment. In this study, we observed that yellow fluorescent protein(+) ASCs in the medullary cords migrated along myelomonocytic cells and arrested in contact with them. Acute ablation of myeloid cells using the human diphtheria receptor system (diphtheria toxin receptor [DTR]) expressed in Lysmd1-cre-positive cells increased ASC and Ab production by 2-fold. Increases in ASC numbers were associated with cell proliferation based on Ki-67 staining, rather than reduced apoptosis, or changes in egress from the LN. Using DTR-mediated ablation targeted to Ccr2-expressing myeloid cells also generated increases in ASCs. In contrast, neither the depletion of Gr-1-positive cells with an Ab nor the ablation of cells using a cd11c-DTR resulted in any change in ASCs. IL-6 cytokine signaling can enhance ASC production and has been implicated in dampening ASCs in lupus mouse models through myeloid cells. Using mixed bone marrow chimeras, we observed that IL-6 enhances ASC production, but IL-6 production was not required by myeloid cells to dampen ASCs in the LN. Inhibition of ASCs by these myeloid cells in the LN provides a new regulatory mechanism with implications for tuning Ab responses. AD - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016; AN - 24376270 AU - Fooksman, D. R. AU - Nussenzweig, M. C. AU - Dustin, M. L. C1 - 3 C2 - PMC3957337 C6 - NIHMS545373 C7 - *** CN - 12855 DA - Feb 1 DO - 10.4049/jimmunol.1300977 DP - Nlm ET - 2014/01/01 J2 - Journal of immunology (Baltimore, Md. : 1950) KW - Adoptive Transfer Animals Animals, Congenic Antibody-Producing Cells/*immunology Apoptosis B-Lymphocyte Subsets/immunology/transplantation Cell Communication Diphtheria Toxin/pharmacology Genes, Reporter Humans Immunization Intercellular Signaling Peptides and Proteins/genetics Interleukin-6/physiology Ki-67 Antigen/analysis Luminescent Proteins/analysis Lymph Nodes/*immunology/ultrastructure Mice Mice, Inbred C57BL Mice, Transgenic Myeloid Cells/drug effects/*immunology Ovalbumin/immunology Promoter Regions, Genetic Radiation Chimera Receptors, CCR2/genetics Recombinant Fusion Proteins/analysis/genetics Transcription Factors/genetics/physiology L1 - internal-pdf://3554285136/Fooksman-2014-Myeloid cells limit production o.pdf LA - eng LB - 24376270 M1 - 3 N1 - 1550-6606 Fooksman, David R Nussenzweig, Michel C Dustin, Michael L Journal Article Research Support, N.I.H., Extramural United States J Immunol. 2014 Feb 1;192(3):1004-12. doi: 10.4049/jimmunol.1300977. Epub 2013 Dec 27. PY - 2014 RI - 2014 from pubmed SN - 0022-1767 SP - 1004-12 ST - Myeloid cells limit production of antibody-secreting cells after immunization in the lymph node T2 - J Immunol TI - Myeloid cells limit production of antibody-secreting cells after immunization in the lymph node TT - R01 AI072529 UR - http://www.jimmunol.org/content/192/3/1004.full.pdf VL - 192 ID - 6 ER - TY - JOUR AB - In vertebrates, the first asymmetries are established along the animal-vegetal axis during oogenesis, but the underlying molecular mechanisms are poorly understood. Bucky ball (Buc) was identified in zebrafish as a novel vertebrate-specific regulator of oocyte polarity, acting through unknown molecular interactions. Here we show that endogenous Buc protein localizes to the Balbiani body, a conserved, asymmetric structure in oocytes that requires Buc for its formation. Asymmetric distribution of Buc in oocytes precedes Balbiani body formation, defining Buc as the earliest marker of oocyte polarity in zebrafish. Through a transgenic strategy, we determined that excess Buc disrupts polarity and results in supernumerary Balbiani bodies in a 3'UTR-dependent manner, and we identified roles for the buc introns in regulating Buc activity. Analyses of mosaic ovaries indicate that oocyte pattern determines the number of animal pole-specific micropylar cells that are associated with an egg via a close-range signal or direct cell contact. We demonstrate interactions between Buc protein and buc mRNA with two conserved RNA-binding proteins (RNAbps) that are localized to the Balbiani body: RNA binding protein with multiple splice isoforms 2 (Rbpms2) and Deleted in azoospermia-like (Dazl). Buc protein and buc mRNA interact with Rbpms2; buc and dazl mRNAs interact with Dazl protein. Cumulatively, these studies indicate that oocyte polarization depends on tight regulation of buc: Buc establishes oocyte polarity through interactions with RNAbps, initiating a feedback amplification mechanism in which Buc protein recruits RNAbps that in turn recruit buc and other RNAs to the Balbiani body. AD - Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. AN - 24496621 AU - Heim, A. E. AU - Hartung, O. AU - Rothhamel, S. AU - Ferreira, E. AU - Jenny, A. AU - Marlow, F. L. C1 - 2 C2 - PMC3912829 C7 - + CN - 12894 DA - Feb DO - 10.1242/dev.090449 DP - Nlm ET - 2014/02/06 J2 - Development (Cambridge, England) KW - Animals Cell Polarity/*physiology Cytoplasmic Structures/metabolism/*physiology Feedback, Physiological/*physiology Genotyping Techniques Immunoprecipitation In Situ Hybridization Oocytes/*physiology Oogenesis/*physiology Plasmids/genetics RNA, Messenger/*metabolism RNA-Binding Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction Two-Hybrid System Techniques Zebrafish Zebrafish Proteins/*metabolism L1 - internal-pdf://1554257660/Heim-2014-Oocyte polarity requires a Bucky bal.pdf internal-pdf://0106764059/Heim-2014-Oocyte polarity requires a Bucky ba1.pdf LA - eng LB - 24496621 M1 - 4 N1 - 1477-9129 Heim, Amanda E Hartung, Odelya Rothhamel, Sophie Ferreira, Elodie Jenny, Andreas Marlow, Florence L Journal Article Research Support, N.I.H., Extramural England Development. 2014 Feb;141(4):842-54. doi: 10.1242/dev.090449. PY - 2014 RI - 2014 from pubmed SN - 0950-1991 SP - 842-54 ST - Oocyte polarity requires a Bucky ball-dependent feedback amplification loop T2 - Development TI - Oocyte polarity requires a Bucky ball-dependent feedback amplification loop TT - R01GM088202 R01GM089979 T32-GM007288 UR - http://dev.biologists.org/content/141/4/842.full.pdf VL - 141 ID - 8 ER - TY - JOUR AB - Macroautophagy (MA) regulates cellular quality control and energy balance. For example, loss of MA in aP2-positive adipocytes converts white adipose tissue (WAT) into brown adipose tissue (BAT)-like, enhancing BAT function and thereby insulin sensitivity. However, whether MA regulates early BAT development is unknown. We report that deleting Atg7 in myogenic Myf5+ progenitors inhibits MA in Myf5-cell-derived BAT and muscle. Knock out (KO) mice have defective BAT differentiation and function. Surprisingly, their body temperature is higher due to WAT lipolysis-driven increases in fatty acid oxidation in 'Beige' cells in inguinal WAT, BAT and muscle. KO mice also present impaired muscle differentiation, reduced muscle mass and glucose intolerance. Our studies show that ATG7 in Myf5+ progenitors is required to maintain energy and glucose homeostasis through effects on BAT and muscle development. Decreased MA in myogenic progenitors with age and/or overnutrition might contribute to the metabolic defects and sarcopenia observed in these conditions. AD - 1] Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. AN - 23907538 AU - Martinez-Lopez, N. AU - Athonvarangkul, D. AU - Sahu, S. AU - Coletto, L. AU - Zong, H. AU - Bastie, C. C. AU - Pessin, J. E. AU - Schwartz, G. J. AU - Singh, R. C1 - 7 C2 - PMC3790054 CN - 12901 DA - Sep DO - 10.1038/embor.2013.111 DP - Nlm ET - 2013/08/03 J2 - EMBO reports KW - Adipose Tissue, Brown/growth & development/*metabolism Animals *Autophagy Cell Differentiation *Energy Metabolism Fatty Acids/metabolism Glucose/*metabolism *Homeostasis Mice Microtubule-Associated Proteins/genetics/metabolism Muscle, Skeletal/growth & development/*metabolism Myogenic Regulatory Factor 5/genetics/*metabolism Stem Cells/cytology/metabolism L1 - internal-pdf://4008318810/Martinez-Lopez-2013-Autophagy in Myf5+ progeni.pdf LA - eng LB - 23907538 M1 - 9 N1 - 1469-3178 Martinez-Lopez, Nuria Athonvarangkul, Diana Sahu, Srabani Coletto, Luisa Zong, Haihong Bastie, Claire C Pessin, Jeffrey E Schwartz, Gary J Singh, Rajat Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England EMBO Rep. 2013 Sep;14(9):795-803. doi: 10.1038/embor.2013.111. Epub 2013 Aug 2. PY - 2013 RI - 2014 from pubmed SN - 1469-221x SP - 795-803 ST - Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development T2 - EMBO Rep TI - Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development TT - 5T32GM728837 AG043517 DK020541 DK033823 DK087776 DK81412 K01 DK087776 R01 AG043517 T32 GM007288 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790054/pdf/embor2013111a.pdf VL - 14 ID - 11 ER - TY - JOUR AB - A rugged sample-preparation method for comprehensive affinity enrichment of phosphopeptides from protein digests has been developed. The method uses a series of chemical reactions to incorporate efficiently and specifically a thiol-functionalized affinity tag into the analyte by barium hydroxide catalyzed beta-elimination with Michael addition using 2-aminoethanethiol as nucleophile and subsequent thiolation of the resulting amino group with sulfosuccinimidyl-2-(biotinamido) ethyl-1,3-dithiopropionate. Gentle oxidation of cysteine residues, followed by acetylation of alpha- and epsilon-amino groups before these reactions, ensured selectivity of reversible capture of the modified phosphopeptides by covalent chromatography on activated thiol sepharose. The use of C18 reversed-phase supports as a miniaturized reaction bed facilitated optimization of the individual modification steps for throughput and completeness of derivatization. Reagents were exchanged directly on the supports, eliminating sample transfer between the reaction steps and thus, allowing the immobilized analyte to be carried through the multistep reaction scheme with minimal sample loss. The use of this sample-preparation method for phosphopeptide enrichment was demonstrated with low-level amounts of in-gel-digested protein. As applied to tryptic digests of alpha-S1- and beta-casein, the method enabled the enrichment and detection of the phosphorylated peptides contained in the mixture, including the tetraphosphorylated species of beta-casein, which has escaped chemical procedures reported previously. The isolates proved highly suitable for mapping the sites of phosphorylation by collisionally induced dissociation. beta-Elimination, with consecutive Michael addition, expanded the use of the solid-phase-based enrichment strategy to phosphothreonyl peptides and to phosphoseryl/phosphothreonyl peptides derived from proline-directed kinase substrates and to their O-sulfono- and O-linked beta-N-acetylglucosamine (O-GlcNAc)-modified counterparts. Solid-phase enzymatic dephosphorylation proved to be a viable tool to condition O-GlcNAcylated peptide in mixtures with phosphopeptides for selective affinity purification. Acetylation, as an integral step of the sample-preparation method, precluded reduction in recovery of the thiolation substrate caused by intrapeptide lysine-dehydroalanine cross-link formation. The solid-phase analytical platform provides robustness and simplicity of operation using equipment readily available in most biological laboratories and is expected to accommodate additional chemistries to expand the scope of solid-phase serial derivatization for protein structural characterization. AD - Laboratory for Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. AN - 23997662 AU - Nika, H. AU - Nieves, E. AU - Hawke, D. H. AU - Angeletti, R. H. C1 - 5 C2 - PMC3750845 CN - 12833 DA - Sep DO - 10.7171/jbt.13-2403-004 DP - Nlm ET - 2013/09/03 J2 - Journal of biomolecular techniques : JBT KW - Amino Acid Sequence Caseins/chemistry Chromatography, Affinity/methods Chromatography, Reverse-Phase Immobilized Proteins/*chemistry Peptide Fragments Phosphopeptides/*chemistry Phosphorylation Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods Trypsin/chemistry L1 - internal-pdf://0089069090/Nika-2013-Phosphopeptide enrichment by covalen.pdf LA - eng LB - 23997662 M1 - 3 N1 - 1943-4731 Nika, Heinz Nieves, Edward Hawke, David H Angeletti, Ruth Hogue Journal Article Research Support, N.I.H., Extramural United States J Biomol Tech. 2013 Sep;24(3):154-77. doi: 10.7171/jbt.13-2403-004. PY - 2013 RI - 2014 from pubmed SN - 1524-0215 SP - 154-77 ST - Phosphopeptide enrichment by covalent chromatography after derivatization of protein digests immobilized on reversed-phase supports T2 - J Biomol Tech TI - Phosphopeptide enrichment by covalent chromatography after derivatization of protein digests immobilized on reversed-phase supports TT - P20-DA026149 R33CA101150 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750845/pdf/jbt13-2403-004.pdf VL - 24 ID - 2 ER - TY - JOUR AB - We previously adapted the beta-elimination/Michael addition chemistry to solid-phase derivatization on reversed-phase supports, and demonstrated the utility of this reaction format to prepare phosphoseryl peptides in unfractionated protein digests for mass spectrometric identification and facile phosphorylation-site determination. Here, we have expanded the use of this technique to beta-N-acetylglucosamine peptides, modified at serine/threonine, phosphothreonyl peptides, and phosphoseryl/phosphothreonyl peptides, followed in sequence by proline. The consecutive beta-elimination with Michael addition was adapted to optimize the solid-phase reaction conditions for throughput and completeness of derivatization. The analyte remained intact during derivatization and was recovered efficiently from the silica-based, reversed-phase support with minimal sample loss. The general use of the solid-phase approach for enzymatic dephosphorylation was demonstrated with phosphoseryl and phosphothreonyl peptides and was used as an orthogonal method to confirm the identity of phosphopeptides in proteolytic mixtures. The solid-phase approach proved highly suitable to prepare substrates from low-level amounts of protein digests for phosphorylation-site determination by chemical-targeted proteolysis. The solid-phase protocol provides for a simple, robust, and efficient tool to prepare samples for phosphopeptide identification in MALDI mass maps of unfractionated protein digests, using standard equipment available in most biological laboratories. The use of a solid-phase analytical platform is expected to be readily expanded to prepare digest from O-glycosylated- and O-sulfonated proteins for mass spectrometry-based structural characterization. AD - Laboratory for Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. AN - 23997661 AU - Nika, H. AU - Nieves, E. AU - Hawke, D. H. AU - Angeletti, R. H. C1 - 5 C2 - PMC3703673 CN - 12834 DA - Sep DO - 10.7171/jbt.13-2403-005 DP - Nlm ET - 2013/09/03 J2 - Journal of biomolecular techniques : JBT KW - Acetylglucosamine/*chemistry Glycosylation Mass Spectrometry Molecular Weight Phosphopeptides/chemical synthesis/*chemistry Phosphorylation Proteolysis Solid-Phase Synthesis Techniques *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization L1 - internal-pdf://0034018850/Nika-2013-Optimization of the beta-elimination.pdf LA - eng LB - 23997661 M1 - 3 N1 - 1943-4731 Nika, Heinz Nieves, Edward Hawke, David H Angeletti, Ruth Hogue Journal Article Research Support, N.I.H., Extramural United States J Biomol Tech. 2013 Sep;24(3):132-53. doi: 10.7171/jbt.13-2403-005. PY - 2013 RI - 2014 from pubmed SN - 1524-0215 SP - 132-53 ST - Optimization of the beta-elimination/michael addition chemistry on reversed-phase supports for mass spectrometry analysis of O-linked protein modifications T2 - J Biomol Tech TI - Optimization of the beta-elimination/michael addition chemistry on reversed-phase supports for mass spectrometry analysis of O-linked protein modifications TT - P20-DA026149 R33CA101150 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703673/pdf/jbt13-2403-005.pdf VL - 24 ID - 3 ER - TY - JOUR AB - Far from now are the days when investigators raced to identify the proteolytic system responsible for the degradation of their favorite protein. Nowadays, it is well accepted that a given protein can be degraded by different systems depending on factors such as cell type, cellular conditions, or functionality of each proteolytic pathway. The realization of this sharing of substrates among pathways has also helped to unveil deeper levels of communication among the different proteolytic systems. Thus, cells often respond to blockage of one degradative mechanism by upregulating any of the other available pathways. In addition, effectors and regulators of one proteolytic system can be degraded by a different proteolytic pathway that exerts, in this way, a regulatory function. In this mini review, we describe the different levels of cross-talk among autophagic pathways and the ubiquitin/proteasome system. We also provide examples of how this proteolytic communication is used for compensatory purposes in different pathological conditions and discuss the possible therapeutic potential of targeting the modulators of the cross-talk among proteolytic pathways. AD - Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, USA. AN - 23709310 AU - Park, C. AU - Cuervo, A. M. C1 - 7 C2 - PMC3758803 C6 - NIHMS485220 CN - 12838 DA - Sep DO - 10.1007/s12013-013-9623-7 DP - Nlm ET - 2013/05/28 J2 - Cell biochemistry and biophysics KW - *Autophagy Humans Molecular Chaperones/metabolism Proteasome Endopeptidase Complex/*metabolism Proteolysis Substrate Specificity Ubiquitin/*metabolism L1 - internal-pdf://2394560080/Park-2013-Selective autophagy_ talking with th.pdf LA - eng LB - 23709310 M1 - 1 N1 - 1559-0283 Park, Caroline Cuervo, Ana Maria Journal Article Review United States Cell Biochem Biophys. 2013 Sep;67(1):3-13. doi: 10.1007/s12013-013-9623-7. PY - 2013 RI - 2014 from pubmed SN - 1085-9195 SP - 3-13 ST - Selective autophagy: talking with the UPS T2 - Cell Biochem Biophys TI - Selective autophagy: talking with the UPS TT - P01 AG031782 R01 AG021904 R01 DK098408 R37 AG021904 T32 GM007288 UR - http://download.springer.com/static/pdf/485/art%253A10.1007%252Fs12013-013-9623-7.pdf?auth66=1397233006_47285857306b1b2e9371203213ebd203&ext=.pdf VL - 67 ID - 5 ER - TY - JOUR AB - Mycobacterium tuberculosis releases membrane vesicles packed with molecules that can modulate the immune response. Because environmental conditions often influence the production and content of bacterial vesicles, this study examined M. tuberculosis microvesicles released under iron limitation, a common condition faced by pathogens inside the host. The findings indicate that M. tuberculosis increases microvesicle production in response to iron restriction and that these microvesicles contain mycobactin, which can serve as an iron donor and supports replication of iron-starved mycobacteria. Consequently, the results revealed a role of microvesicles in iron acquisition in M. tuberculosis, which can be critical for survival in the host. AD - Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA. AN - 24415729 AU - Prados-Rosales, R. AU - Weinrick, B. C. AU - Pique, D. G. AU - Jacobs, W. R., Jr. AU - Casadevall, A. AU - Rodriguez, G. M. C1 - 5 C2 - PMC3957709 CN - 13094 DA - Mar DO - 10.1128/jb.01090-13 DP - Nlm ET - 2014/01/15 J2 - Journal of bacteriology KW - Exosomes/*metabolism Iron/*metabolism Mycobacterium tuberculosis/*metabolism Oxazoles/metabolism Transport Vesicles/*metabolism L1 - internal-pdf://1811289977/Prados-Rosales-2014-Role for Mycobacterium tub.pdf LA - eng LB - 24415729 M1 - 6 N1 - 1098-5530 Prados-Rosales, Rafael Weinrick, Brian C Pique, Daniel G Jacobs, William R Jr Casadevall, Arturo Rodriguez, G Marcela Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States J Bacteriol. 2014 Mar;196(6):1250-6. doi: 10.1128/JB.01090-13. Epub 2014 Jan 10. PY - 2014 RI - 2014 from pubmed SN - 0021-9193 SP - 1250-6 ST - Role for Mycobacterium tuberculosis membrane vesicles in iron acquisition T2 - J Bacteriol TI - Role for Mycobacterium tuberculosis membrane vesicles in iron acquisition TT - AI044856 UR - http://jb.asm.org/content/196/6/1250.full.pdf VL - 196 ID - 14 ER - TY - JOUR AB - Standard methods for mitochondrial DNA (mtDNA) extraction do not provide the level of enrichment for mtDNA sufficient for direct sequencing and must be followed by long-range-PCR amplification, which can bias the sequencing results. Here, we describe a fast, cost-effective, and reliable method for preparation of mtDNA enriched samples from eukaryotic cells ready for direct sequencing. Our protocol utilizes a conventional miniprep kit, paramagnetic bead-based purification, and an optional, limited PCR amplification of mtDNA. The first two steps alone provide more than 2000-fold enrichment for mtDNA when compared with total cellular DNA (~200-fold in comparison with current commercially available kits) as demonstrated by real-time PCR. The percentage of sequencing reads aligned to mtDNA was about 22% for non-amplified samples and greater than 99% for samples subjected to 10 cycles of long-range-PCR with mtDNA specific primers. AD - Albert Einstein College of Medicine, Department of Genetics, New York, NY, USA. AN - 24003945 AU - Quispe-Tintaya, W. AU - White, R. R. AU - Popov, V. N. AU - Vijg, J. AU - Maslov, A. Y. C1 - 7 CN - 12832 DA - Sep DO - 10.2144/000114077 DP - Nlm ET - 2013/09/06 J2 - BioTechniques KW - Animals Biotechnology/methods Cell Line DNA, Mitochondrial/chemistry/genetics/*isolation & purification High-Throughput Nucleotide Sequencing/*methods Mice Polymerase Chain Reaction Sequence Alignment Sequence Analysis, DNA/*methods LA - eng LB - 24003945 M1 - 3 N1 - 1940-9818 Quispe-Tintaya, Wilber White, Ryan R Popov, Vasily N Vijg, Jan Maslov, Alexander Y Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Biotechniques. 2013 Sep;55(3):133-6. doi: 10.2144/000114077. PY - 2013 RI - 2014 from pubmed SN - 0736-6205 SP - 133-6 ST - Fast mitochondrial DNA isolation from mammalian cells for next-generation sequencing T2 - Biotechniques TI - Fast mitochondrial DNA isolation from mammalian cells for next-generation sequencing TT - P01 AG017242 VL - 55 ID - 1 ER - TY - JOUR AB - PURPOSE OF REVIEW: In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. RECENT FINDINGS: Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. SUMMARY: There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection. AD - Division of Oncology, Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467, USA. AN - 23942294 AU - Shcherba, M. AU - Shuter, J. AU - Haigentz, M., Jr. C1 - 5 C2 - PMC3906041 C6 - NIHMS539984 C7 - + CN - 12836 DA - Sep DO - 10.1097/CCO.0b013e328363dfdb DP - Nlm ET - 2013/08/15 J2 - Current opinion in oncology KW - Age of Onset HIV Infections/*complications Humans Immunosuppression/adverse effects Lung Neoplasms/diagnosis/*etiology Risk Factors Smoking/adverse effects L1 - internal-pdf://0209458753/Shcherba-2013-Current questions in HIV-associa.pdf LA - eng LB - 23942294 M1 - 5 N1 - 1531-703x Shcherba, Marina Shuter, Jonathan Haigentz, Missak Jr Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States Curr Opin Oncol. 2013 Sep;25(5):511-7. doi: 10.1097/CCO.0b013e328363dfdb. PY - 2013 RI - 2014 from pubmed SN - 1040-8746 SP - 511-7 ST - Current questions in HIV-associated lung cancer T2 - Curr Opin Oncol TI - Current questions in HIV-associated lung cancer TT - P30 AI051519 U01 CA121947 U01CA121947 UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCMCEHICCO00/fs046/ovft/live/gv023/00001622/00001622-201309000-00010.pdf VL - 25 ID - 4 ER - TY - JOUR AD - Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, New York 10467-2490, USA. vthiruko@montefiore.org AN - 23271267 AU - Thirukonda, V. AU - Petrich, A. AU - Parekh, S. C1 - 3 CN - 11057 DA - Nov DP - Nlm ET - 2012/12/29 KW - Aged, 80 and over Female Hodgkin Disease/diagnosis/*pathology Humans *Neoplasm Regression, Spontaneous LA - eng LB - 23271267 M1 - 11 N1 - Thirukonda, Venu Petrich, Adam Parekh, Samir Case Reports Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States Clinical advances in hematology & oncology : H&O Clin Adv Hematol Oncol. 2012 Nov;10(11):765-6. PY - 2012 RI - 2012 from pubmed SN - 1543-0790 (Print) 1543-0790 (Linking) SP - 765-6 ST - Classical Hodgkin lymphoma and spontaneous regression T2 - Clin Adv Hematol Oncol TI - Classical Hodgkin lymphoma and spontaneous regression TT - CA132783-01 UR - http://www.ncbi.nlm.nih.gov/pubmed/23271267 VL - 10 ID - 13 ER - TY - JOUR AB - Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG's (58.5%) in HIV-1 proviral genomes including ten CpG's in each LTR and additional CpG's in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC's of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG's regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG's suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC's. Unmethylated CpG's may play a role in HIV-1 immunopathogenesis. AD - Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany. University of California, Davis School of Medicine and Sacramento Veterans Administration Medical Center, Sacramento, CA 95655, USA. Albert Einstein College of Medicine, Bronx, NY 10461, USA. University of California, Los Angeles, CA 90095, USA. University of Toronto, Toronto, ON, Canada M55 1A8. Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany; Institute of Genetics, University of Cologne, D-50674 Cologne, Germany. Electronic address: walter.doerfler@viro.med.uni-erlangen.de. AN - 24418551 AU - Weber, S. AU - Weiser, B. AU - Kemal, K. S. AU - Burger, H. AU - Ramirez, C. M. AU - Korn, K. AU - Anastos, K. AU - Kaul, R. AU - Kovacs, C. AU - Doerfler, W. C1 - 6 CN - 12895 DA - Jan 20 DO - 10.1016/j.virol.2013.11.013 DP - Nlm ET - 2014/01/15 J2 - Virology KW - Adult Cells, Cultured DNA Methylation Dinucleoside Phosphates/*genetics *Epigenesis, Genetic Female *Genome, Viral HIV Infections/*virology HIV-1/*genetics/physiology Humans Leukocytes, Mononuclear/virology Male Proviruses/*genetics/physiology Young Adult L1 - internal-pdf://2246186795/Weber-2014-Epigenetic analysis of HIV-1 provir.pdf internal-pdf://2652837675/Weber-2014-Epigenetic analysis of HIV-1 provi1.pdf LA - eng LB - 24418551 N1 - 1096-0341 Weber, Stefanie Weiser, Barbara Kemal, Kimdar S Burger, Harold Ramirez, Christina M Korn, Klaus Anastos, Kathryn Kaul, Rupert Kovacs, Colin Doerfler, Walter Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Virology. 2014 Jan 20;449:181-9. doi: 10.1016/j.virol.2013.11.013. Epub 2013 Dec 5. PY - 2014 RI - 2014 from pubmed SN - 0042-6822 SP - 181-9 ST - Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's T2 - Virology TI - Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's TT - HET-85518 U01 AI035004 UO1-AI35004 UR - http://ac.els-cdn.com/S0042682213006260/1-s2.0-S0042682213006260-main.pdf?_tid=0115200c-c3f1-11e3-a688-00000aab0f27&acdnat=1397492742_a34a49de0e6f859489a3defcdcdf5a15 http://ac.els-cdn.com/S0042682213006260/1-s2.0-S0042682213006260-main.pdf?_tid=40c4b3d2-ca60-11e3-a368-00000aab0f02&acdnat=1398200230_9608aa25835b090a4407538e720e3ac2 VL - 449 ID - 9 ER - TY - JOUR AB - Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG's (58.5%) in HIV-1 proviral genomes including ten CpG's in each LTR and additional CpG's in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC's of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG's regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG's suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC's. Unmethylated CpG's may play a role in HIV-1 immunopathogenesis. AD - Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany. University of California, Davis School of Medicine and Sacramento Veterans Administration Medical Center, Sacramento, CA 95655, USA. Albert Einstein College of Medicine, Bronx, NY 10461, USA. University of California, Los Angeles, CA 90095, USA. University of Toronto, Toronto, ON, Canada M55 1A8. Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany; Institute of Genetics, University of Cologne, D-50674 Cologne, Germany. Electronic address: walter.doerfler@viro.med.uni-erlangen.de. AN - 24418551 AU - Weber, S. AU - Weiser, B. AU - Kemal, K. S. AU - Burger, H. AU - Ramirez, C. M. AU - Korn, K. AU - Anastos, K. AU - Kaul, R. AU - Kovacs, C. AU - Doerfler, W. C1 - 6 CN - 12910 DA - Jan 20 DO - 10.1016/j.virol.2013.11.013 DP - NLM ET - 2014/01/15 J2 - Virology KW - Adult Cells, Cultured DNA Methylation Dinucleoside Phosphates/*genetics *Epigenesis, Genetic Female *Genome, Viral HIV Infections/*virology HIV-1/*genetics/physiology Humans Leukocytes, Mononuclear/virology Male Proviruses/*genetics/physiology Young Adult Bisulfite sequencing Epigenetics of HIV-1 proviral DNA Escape from proviral DNA methylation Fluctuation of CpG methylation in one LTNP individual Integrated HIV-1 DNA in PBMC's from infected individuals Methylation analysis of integrated HIV-1 genomes Predominance of unmethylated CpG's in PBMC's Wide spectrum of infection outcome L1 - internal-pdf://1676679017/Weber-2014-Epigenetic analysis of HIV-1 provir.pdf LA - eng LB - 24418551 N1 - 1096-0341 Weber, Stefanie Weiser, Barbara Kemal, Kimdar S Burger, Harold Ramirez, Christina M Korn, Klaus Anastos, Kathryn Kaul, Rupert Kovacs, Colin Doerfler, Walter Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Virology. 2014 Jan 20;449:181-9. doi: 10.1016/j.virol.2013.11.013. Epub 2013 Dec 5. PY - 2014 RI - 2014 from pubmed SN - 0042-6822 SP - 181-9 ST - Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's T2 - Virology TI - Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's TT - HET-85518 U01 AI035004 UO1-AI35004 UR - http://ac.els-cdn.com/S0042682213006260/1-s2.0-S0042682213006260-main.pdf?_tid=b1afa0c0-ca60-11e3-855d-00000aab0f01&acdnat=1398200419_0736eb62b552779b5e6533220cd8136d VL - 449 ID - 12 ER -