ALBERT

Description: Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a 〉40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model.

Description: HLA-DM is a major histocompatibility complex (MHC) class II-like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides (CLIP) from class II molecules for antigenic peptides. HLA-DO is a second class II-like molecule that physically associates with HLA-DM in B cells. HLA-DO was shown to block HLA-DM function. Purified HLA-DM-DO complexes could not promote peptide exchange in vitro. Expression of HLA-DO in a class II+ and DM+, DO- human T cell line caused the accumulation of class II-CLIP complexes, indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denzin, L K -- Sant'Angelo, D B -- Hammond, C -- Surman, M J -- Cresswell, P -- AI14579/AI/NIAID NIH HHS/ -- AI23081/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 3;278(5335):106-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9311912" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammond, William C -- New York, N.Y. -- Science. 2005 Dec 2;310(5753):1440-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nevada Bureau of Mines and Geology, University of Nevada, Reno, Reno NV 89557-0088, USA. whammond@unr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16322443" target="_blank"〉PubMed〈/a〉

Description: Relative travel time delays of teleseismic P and S waves, recorded during the Mantle Electromagnetic and Tomography (MELT) Experiment, have been inverted tomographically for upper-mantle structure beneath the southern East Pacific Rise. A broad zone of low seismic velocities extends beneath the rise to depths of about 200 kilometers and is centered to the west of the spreading center. The magnitudes of the P and S wave anomalies require the presence of retained mantle melt; the melt fraction near the rise exceeds the fraction 300 kilometers off axis by as little as 1%. Seismic anisotropy, induced by mantle flow, is evident in the P wave delays at near-vertical incidence and is consistent with a half-width of mantle upwelling of about 100 km.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toomey -- Wilcock -- Solomon -- Hammond -- Orcutt -- New York, N.Y. -- Science. 1998 May 22;280(5367):1224-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D. R. Toomey and W. C. Hammond, Department of Geological Sciences, University of Oregon, Eugene, OR 97403, USA. W. S. D. Wilcock, School of Oceanography, University of Washington, Seattle, WA 98195, USA. S. C. Solomon, Department of Terrestrial.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9596567" target="_blank"〉PubMed〈/a〉

Description: Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335296/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gieger, Christian -- Radhakrishnan, Aparna -- Cvejic, Ana -- Tang, Weihong -- Porcu, Eleonora -- Pistis, Giorgio -- Serbanovic-Canic, Jovana -- Elling, Ulrich -- Goodall, Alison H -- Labrune, Yann -- Lopez, Lorna M -- Magi, Reedik -- Meacham, Stuart -- Okada, Yukinori -- Pirastu, Nicola -- Sorice, Rossella -- Teumer, Alexander -- Voss, Katrin -- Zhang, Weihua -- Ramirez-Solis, Ramiro -- Bis, Joshua C -- Ellinghaus, David -- Gogele, Martin -- Hottenga, Jouke-Jan -- Langenberg, Claudia -- Kovacs, Peter -- O'Reilly, Paul F -- Shin, So-Youn -- Esko, Tonu -- Hartiala, Jaana -- Kanoni, Stavroula -- Murgia, Federico -- Parsa, Afshin -- Stephens, Jonathan -- van der Harst, Pim -- Ellen van der Schoot, C -- Allayee, Hooman -- Attwood, Antony -- Balkau, Beverley -- Bastardot, Francois -- Basu, Saonli -- Baumeister, Sebastian E -- Biino, Ginevra -- Bomba, Lorenzo -- Bonnefond, Amelie -- Cambien, Francois -- Chambers, John C -- Cucca, Francesco -- D'Adamo, Pio -- Davies, Gail -- de Boer, Rudolf A -- de Geus, Eco J C -- Doring, Angela -- Elliott, Paul -- Erdmann, Jeanette -- Evans, David M -- Falchi, Mario -- Feng, Wei -- Folsom, Aaron R -- Frazer, Ian H -- Gibson, Quince D -- Glazer, Nicole L -- Hammond, Chris -- Hartikainen, Anna-Liisa -- Heckbert, Susan R -- Hengstenberg, Christian -- Hersch, Micha -- Illig, Thomas -- Loos, Ruth J F -- Jolley, Jennifer -- Khaw, Kay Tee -- Kuhnel, Brigitte -- Kyrtsonis, Marie-Christine -- Lagou, Vasiliki -- Lloyd-Jones, Heather -- Lumley, Thomas -- Mangino, Massimo -- Maschio, Andrea -- Mateo Leach, Irene -- McKnight, Barbara -- Memari, Yasin -- Mitchell, Braxton D -- Montgomery, Grant W -- Nakamura, Yusuke -- Nauck, Matthias -- Navis, Gerjan -- Nothlings, Ute -- Nolte, Ilja M -- Porteous, David J -- Pouta, Anneli -- Pramstaller, Peter P -- Pullat, Janne -- Ring, Susan M -- Rotter, Jerome I -- Ruggiero, Daniela -- Ruokonen, Aimo -- Sala, Cinzia -- Samani, Nilesh J -- Sambrook, Jennifer -- Schlessinger, David -- Schreiber, Stefan -- Schunkert, Heribert -- Scott, James -- Smith, Nicholas L -- Snieder, Harold -- Starr, John M -- Stumvoll, Michael -- Takahashi, Atsushi -- Tang, W H Wilson -- Taylor, Kent -- Tenesa, Albert -- Lay Thein, Swee -- Tonjes, Anke -- Uda, Manuela -- Ulivi, Sheila -- van Veldhuisen, Dirk J -- Visscher, Peter M -- Volker, Uwe -- Wichmann, H-Erich -- Wiggins, Kerri L -- Willemsen, Gonneke -- Yang, Tsun-Po -- Hua Zhao, Jing -- Zitting, Paavo -- Bradley, John R -- Dedoussis, George V -- Gasparini, Paolo -- Hazen, Stanley L -- Metspalu, Andres -- Pirastu, Mario -- Shuldiner, Alan R -- Joost van Pelt, L -- Zwaginga, Jaap-Jan -- Boomsma, Dorret I -- Deary, Ian J -- Franke, Andre -- Froguel, Philippe -- Ganesh, Santhi K -- Jarvelin, Marjo-Riitta -- Martin, Nicholas G -- Meisinger, Christa -- Psaty, Bruce M -- Spector, Timothy D -- Wareham, Nicholas J -- Akkerman, Jan-Willem N -- Ciullo, Marina -- Deloukas, Panos -- Greinacher, Andreas -- Jupe, Steve -- Kamatani, Naoyuki -- Khadake, Jyoti -- Kooner, Jaspal S -- Penninger, Josef -- Prokopenko, Inga -- Stemple, Derek -- Toniolo, Daniela -- Wernisch, Lorenz -- Sanna, Serena -- Hicks, Andrew A -- Rendon, Augusto -- Ferreira, Manuel A -- Ouwehand, Willem H -- Soranzo, Nicole -- 092731/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- CZB/4/505/Chief Scientist Office/United Kingdom -- ETM/55/Chief Scientist Office/United Kingdom -- G0000111/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K12 RR023250/RR/NCRR NIH HHS/ -- K12 RR023250-05/RR/NCRR NIH HHS/ -- M01 RR016500/RR/NCRR NIH HHS/ -- M01 RR016500-08/RR/NCRR NIH HHS/ -- MC_U105260799/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- N01 HC055015/HC/NHLBI NIH HHS/ -- N01 HC055016/HC/NHLBI NIH HHS/ -- N01 HC055018/HC/NHLBI NIH HHS/ -- N01 HC055019/HC/NHLBI NIH HHS/ -- N01 HC055020/HC/NHLBI NIH HHS/ -- N01 HC055021/HC/NHLBI NIH HHS/ -- N01 HC055022/HC/NHLBI NIH HHS/ -- N01 HC085079/HC/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL076491-09/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P01 HL098055-03/HL/NHLBI NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- P30 DK072488-08/DK/NIDDK NIH HHS/ -- P41 HG003751/HG/NHGRI NIH HHS/ -- R01 AG018728/AG/NIA NIH HHS/ -- R01 AG018728-05S1/AG/NIA NIH HHS/ -- R01 GM053275/GM/NIGMS NIH HHS/ -- R01 GM053275-14/GM/NIGMS NIH HHS/ -- R01 HD042157/HD/NICHD NIH HHS/ -- R01 HD042157-01A1/HD/NICHD NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL059367-11/HL/NHLBI NIH HHS/ -- R01 HL068986/HL/NHLBI NIH HHS/ -- R01 HL068986-06/HL/NHLBI NIH HHS/ -- R01 HL073410/HL/NHLBI NIH HHS/ -- R01 HL073410-08/HL/NHLBI NIH HHS/ -- R01 HL085251/HL/NHLBI NIH HHS/ -- R01 HL085251-04/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087641-03/HL/NHLBI NIH HHS/ -- R01 HL087679-03/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 HL088119-04/HL/NHLBI NIH HHS/ -- R01 HL103866/HL/NHLBI NIH HHS/ -- R01 HL103866-03/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RL1 MH083268/MH/NIMH NIH HHS/ -- RL1 MH083268-05/MH/NIMH NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- U54 RR020278-06/RR/NCRR NIH HHS/ -- UL1 RR025005/RR/NCRR NIH HHS/ -- UL1 RR025005-05/RR/NCRR NIH HHS/ -- WT077037/Z/05/Z/Wellcome Trust/United Kingdom -- WT077047/Z/05/Z/Wellcome Trust/United Kingdom -- WT082597/Z/07/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Nov 30;480(7376):201-8. doi: 10.1038/nature10659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstr 1, 85764 Neuherberg, Germany. christian.gieger@helmholtz-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22139419" target="_blank"〉PubMed〈/a〉

Description: Groundwater use in California's San Joaquin Valley exceeds replenishment of the aquifer, leading to substantial diminution of this resource and rapid subsidence of the valley floor. The volume of groundwater lost over the past century and a half also represents a substantial reduction in mass and a large-scale unburdening of the lithosphere, with significant but unexplored potential impacts on crustal deformation and seismicity. Here we use vertical global positioning system measurements to show that a broad zone of rock uplift of up to 1-3 mm per year surrounds the southern San Joaquin Valley. The observed uplift matches well with predicted flexure from a simple elastic model of current rates of water-storage loss, most of which is caused by groundwater depletion. The height of the adjacent central Coast Ranges and the Sierra Nevada is strongly seasonal and peaks during the dry late summer and autumn, out of phase with uplift of the valley floor during wetter months. Our results suggest that long-term and late-summer flexural uplift of the Coast Ranges reduce the effective normal stress resolved on the San Andreas Fault. This process brings the fault closer to failure, thereby providing a viable mechanism for observed seasonality in microseismicity at Parkfield and potentially affecting long-term seismicity rates for fault systems adjacent to the valley. We also infer that the observed contemporary uplift of the southern Sierra Nevada previously attributed to tectonic or mantle-derived forces is partly a consequence of human-caused groundwater depletion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amos, Colin B -- Audet, Pascal -- Hammond, William C -- Burgmann, Roland -- Johanson, Ingrid A -- Blewitt, Geoffrey -- England -- Nature. 2014 May 22;509(7501):483-6. doi: 10.1038/nature13275. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geology Department, Western Washington University, Bellingham, Washington 98225-9080, USA. ; Department of Earth Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. ; Nevada Geodetic Laboratory, Nevada Bureau of Mines and Geology and Nevada Seismological Laboratory, University of Nevada, Reno, Nevada 89557, USA. ; 1] Berkeley Seismological Laboratory, University of California, Berkeley, California 94720-4760, USA [2] Department of Earth and Planetary Science, University of California, Berkeley, California 97720-4767, USA. ; Berkeley Seismological Laboratory, University of California, Berkeley, California 94720-4760, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828048" target="_blank"〉PubMed〈/a〉

Description: The endoplasmic reticulum (ER) contains molecular chaperones that facilitate the folding of proteins in mammalian cells. Biosynthetic labeling was used to study the interactions of two chaperones, BiP and calnexin, with vesicular stomatitis virus (VSV) glycoprotein (G protein). Coimmunoprecipitation of G protein with the chaperones showed that BiP bound maximally to early folding intermediates of G protein, whereas calnexin bound after a short lag to more folded molecules. Castanospermine, an inhibitor of ER glucosidases, blocked the binding of proteins to calnexin and inhibited G protein folding. Interaction with calnexin was necessary for efficient folding of G protein and for retention of partially folded forms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammond, C -- Helenius, A -- P01 CA46128/CA/NCI NIH HHS/ -- R01 GM38346/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Oct 21;266(5184):456-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939687" target="_blank"〉PubMed〈/a〉

Description: Riboswitches are structured RNAs typically located in the 5' untranslated regions of bacterial mRNAs that bind metabolites and control gene expression. Most riboswitches sense one metabolite and function as simple genetic switches. However, we found that the 5' region of the Bacillus clausii metE messenger RNA includes two riboswitches that respond to S-adenosylmethionine and coenzyme B12. This tandem arrangement yields a composite gene control system that functions as a two-input Boolean NOR logic gate. These findings and the discovery of additional tandem riboswitch architectures reveal how simple RNA elements can be assembled to make sophisticated genetic decisions without involving protein factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudarsan, Narasimhan -- Hammond, Ming C -- Block, Kirsten F -- Welz, Rudiger -- Barrick, Jeffrey E -- Roth, Adam -- Breaker, Ronald R -- GM 068819/GM/NIGMS NIH HHS/ -- GM 07223-31/GM/NIGMS NIH HHS/ -- R01 GM068819/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 13;314(5797):300-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, Post Office Box 208103, New Haven, CT 06520-8103, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17038623" target="_blank"〉PubMed〈/a〉

Description: 3-Methylindole, a ruminal fermentation product of tryptophan, induces acute pulmonary edema and emphysema in cattle, and 3-methylindole is present in the ruminal fluid and blood of cows with a natually occurring form of this disease. Monensin, a polyether antibiotic and widely used feed additive for beef cattle, prevented tryptophan-induced acute bovine pulmonary edema and emphysema. Monensin acted by reducing the ruminal conversion of L-tryptophan to 3-methylindole both in vitro and in vivo. Lasalocid, also a polyether antibiotic, showed similar effects in vitro. These results provide a promising approach to prevention of this major respiratory disease of cattle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammond, A C -- Carlson, J R -- Breeze, R G -- New York, N.Y. -- Science. 1978 Jul 14;201(4351):153-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/663643" target="_blank"〉PubMed〈/a〉

Description: Preliminary analysis of radar altimeter data indicates that the instrument has met its specifications for measuring spacecraft height above the ocean surface (+/- 10 centimeters) and significant wave height (+/- 0.5 meter). There is ample evidence that the radar altimeter, having undergone development through three earth orbit missions [Skylab, Geodynamics Experimental Ocean Satellite 3 (GEOS-3), and Seasat], has reached a level of precision that now makes possible its use for important quantitative oceanographic investigations and practical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tapley, B D -- Born, G H -- Hagar, H H -- Lorell, J -- Parke, M E -- Diamante, J M -- Douglas, B C -- Goad, C C -- Kolenkiewicz, R -- Marsh, J G -- Martin, C F -- Smith, S L 3rd -- Townsend, W F -- Whitehead, J A -- Byrne, H M -- Fedor, L S -- Hammond, D C -- Mognard, N M -- New York, N.Y. -- Science. 1979 Jun 29;204(4400):1410-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17814198" target="_blank"〉PubMed〈/a〉