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Science Translational Medicine

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https://www.readbyqxmd.com/read/28637928/the-long-noncoding-rna-wisper-controls-cardiac-fibrosis-and-remodeling
#1
Rudi Micheletti, Isabelle Plaisance, Brian J Abraham, Alexandre Sarre, Ching-Chia Ting, Michael Alexanian, Daniel Maric, Damien Maison, Mohamed Nemir, Richard A Young, Blanche Schroen, Arantxa González, Samir Ounzain, Thierry Pedrazzini
Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified Wisper (Wisp2 super-enhancer-associated RNA) as a cardiac fibroblast-enriched lncRNA that regulates cardiac fibrosis after injury. Wisper expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637927/-amp-k-ed-up-recovery-from-ischemia-reperfusion-injury
#2
Benjamin Levi
Aging decreases tolerance to ischemia-reperfusion injury, which is mitigated by sestrin2-driven substrate metabolism.
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637926/when-they-go-low-we-go-high
#3
Kafui Dzirasa
High-frequency electrical interference can be used to drive activity deep in the brain.
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637925/flipping-the-kill-switch
#4
Stephanie A Christenson
Alveolar macrophages display an impairment in delayed bacterial killing in chronic obstructive pulmonary disease (COPD) that may contribute to an increased susceptibility to bacterial infection.
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637924/vp4-and-vp7-specific-antibodies-mediate-heterotypic-immunity-to-rotavirus-in-humans
#5
Nitya Nair, Ningguo Feng, Lisa K Blum, Mrinmoy Sanyal, Siyuan Ding, Baoming Jiang, Adrish Sen, John M Morton, Xiao-Song He, William H Robinson, Harry B Greenberg
Human rotaviruses (RVs) are the leading cause of severe diarrhea in young children worldwide. The molecular mechanisms underlying the rapid induction of heterotypic protective immunity to RV, which provides the basis for the efficacy of licensed monovalent RV vaccines, have remained unknown for more than 30 years. We used RV-specific single cell-sorted intestinal B cells from human adults, barcode-based deep sequencing of antibody repertoires, monoclonal antibody expression, and serologic and functional characterization to demonstrate that infection-induced heterotypic immunoglobulins (Igs) primarily directed to VP5*, the stalk region of the RV attachment protein, VP4, are able to mediate heterotypic protective immunity...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637923/infectivity-of-plasmodium-falciparum-sporozoites-determines-emerging-parasitemia-in-infected-volunteers
#6
Matthew B B McCall, Linda J Wammes, Marijke C C Langenberg, Geert-Jan van Gemert, Jona Walk, Cornelus C Hermsen, Wouter Graumans, Rob Koelewijn, Jean-François Franetich, Sandra Chishimba, Max Gerdsen, Audrey Lorthiois, Marga van de Vegte, Dominique Mazier, Else M Bijker, Jaap J van Hellemond, Perry J J van Genderen, Robert W Sauerwein
Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical Plasmodium falciparum isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among P...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637922/targeting-factor-d-of-the-alternative-complement-pathway-reduces-geographic-atrophy-progression-secondary-to-age-related-macular-degeneration
#7
Brian L Yaspan, David F Williams, Frank G Holz, Carl D Regillo, Zhengrong Li, Amy Dressen, Menno van Lookeren Campagne, Kha N Le, Robert R Graham, Tatiana Beres, Tushar R Bhangale, Lee A Honigberg, Ashley Smith, Erin C Henry, Carole Ho, Erich C Strauss
Geographic atrophy is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are no approved treatments. Genetic studies in AMD patients have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy. Lampalizumab is a potential therapeutic that targets complement factor D, a pivotal activator of the alternative complement pathway. The MAHALO phase 2 clinical trial was a multicenter, randomized, controlled study that evaluated lampalizumab administered by intravitreal injection monthly (n = 42) and every other month (n = 41) versus sham control (n = 40) in patients with geographic atrophy secondary to AMD...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615363/neutrophils-double-agents-for-tb
#8
Jennifer A Philips
Nitric oxide restricts growth of Mycobacterium tuberculosis by repressing neutrophilic inflammation.
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615362/drugging-the-catalytically-inactive-state-of-ret-kinase-in-ret-rearranged-tumors
#9
Dennis Plenker, Maximilian Riedel, Johannes Brägelmann, Marcel A Dammert, Rakhee Chauhan, Phillip P Knowles, Carina Lorenz, Marina Keul, Mike Bührmann, Oliver Pagel, Verena Tischler, Andreas H Scheel, Daniel Schütte, Yanrui Song, Justina Stark, Florian Mrugalla, Yannic Alber, André Richters, Julian Engel, Frauke Leenders, Johannes M Heuckmann, Jürgen Wolf, Joachim Diebold, Georg Pall, Martin Peifer, Maarten Aerts, Kris Gevaert, René P Zahedi, Reinhard Buettner, Kevan M Shokat, Neil Q McDonald, Stefan M Kast, Oliver Gautschi, Roman K Thomas, Martin L Sos
Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615361/targeting-kras-dependent-tumors-with-azd4785-a-high-affinity-therapeutic-antisense-oligonucleotide-inhibitor-of-kras
#10
Sarah J Ross, Alexey S Revenko, Lyndsey L Hanson, Rebecca Ellston, Anna Staniszewska, Nicky Whalley, Sanjay K Pandey, Mitchell Revill, Claire Rooney, Linda K Buckett, Stephanie K Klein, Kevin Hudson, Brett P Monia, Michael Zinda, David C Blakey, Paul D Lyne, A Robert Macleod
Activating mutations in KRAS underlie the pathogenesis of up to 20% of human tumors, and KRAS is one of the most frequently mutated genes in cancer. Developing therapeutics to block KRAS activity has proven difficult, and no direct inhibitor of KRAS function has entered clinical trials. We describe the preclinical evaluation of AZD4785, a high-affinity constrained ethyl-containing therapeutic antisense oligonucleotide (ASO) targeting KRAS mRNA. AZD4785 potently and selectively depleted cellular KRAS mRNA and protein, resulting in inhibition of downstream effector pathways and antiproliferative effects selectively in KRAS mutant cells...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615360/a-vitamin-to-d-crease-sunburn
#11
Tiffany C Scharschmidt
High doses of oral vitamin D3 attenuate skin inflammation following experimentally induced sun damage.
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615359/immunity-at-the-forefront-of-the-brain-a-new-genetic-model-of-ftd
#12
Jill K Morris
Functional characterization of a genetic variant linked to frontotemporal dementia in a murine model reveals deficits in cerebral immune response and metabolism.
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615358/it-s-reticulated-diabetes-atherosclerosis-and-reticulated-platelets
#13
Kathryn Dupnik
New research describes regulatory pathways for reticulated thrombocytosis in a mouse model of diabetes.
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615357/donor-pulmonary-intravascular-nonclassical-monocytes-recruit-recipient-neutrophils-and-mediate-primary-lung-allograft-dysfunction
#14
Zhikun Zheng, Stephen Chiu, Mahzad Akbarpour, Haiying Sun, Paul A Reyfman, Kishore R Anekalla, Hiam Abdala-Valencia, Daphne Edgren, Wenjun Li, Daniel Kreisel, Farida V Korobova, Ramiro Fernandez, Alexandra McQuattie-Pimentel, Zheng J Zhang, Harris Perlman, Alexander V Misharin, G R Scott Budinger, Ankit Bharat
Primary graft dysfunction is the predominant driver of mortality and graft loss after lung transplantation. Recruitment of neutrophils as a result of ischemia-reperfusion injury is thought to cause primary graft dysfunction; however, the mechanisms that regulate neutrophil influx into the injured lung are incompletely understood. We found that donor-derived intravascular nonclassical monocytes (NCMs) are retained in human and murine donor lungs used in transplantation and can be visualized at sites of endothelial injury after reperfusion...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615356/sulforaphane-reduces-hepatic-glucose-production-and-improves-glucose-control-in-patients-with-type-2-diabetes
#15
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M J Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, Anders H Rosengren
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28592570/editorial-retraction
#16
Jeremy M Berg, Orla M Smith
No abstract text is available yet for this article.
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28592569/rett-syndrome-modeling-goes-simian
#17
Gaia Novarino
Rett syndrome modeling in monkey mirrors the human disorder.
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28592568/congenital-zika-virus-infection-more-than-just-microcephaly
#18
Jonathan J Miner
A nonhuman primate model demonstrates efficient vertical transmission of Zika virus.
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28592567/driver-mutations-take-the-wheel-in-invasive-yet-nonmalignant-disease
#19
Miles A Miller
Despite their low risk for malignant transformation, infiltrating endometriotic lesions harbor cancer-associated mutations.
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28592566/combined-immune-checkpoint-blockade-as-a-therapeutic-strategy-for-brca1-mutated-breast-cancer
#20
Emma Nolan, Peter Savas, Antonia N Policheni, Phillip K Darcy, François Vaillant, Christopher P Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B Pang, Stephen B Fox, Charles M Perou, Jane E Visvader, Daniel H D Gray, Sherene Loi, Geoffrey J Lindeman
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model...
June 7, 2017: Science Translational Medicine
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