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Science Translational Medicine

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https://www.readbyqxmd.com/read/27903866/nigral-dopaminergic-pak4-prevents-neurodegeneration-in-rat-models-of-parkinson-s-disease
#1
So-Yoon Won, Mee-Hee Park, Soon-Tae You, Seung-Won Choi, Hyong-Kyu Kim, Catriona McLean, Suk-Chul Bae, Sang Ryong Kim, Byung Kwan Jin, Kun Ho Lee, Eun-Young Shin, Eung-Gook Kim
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons. We observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from PD patients and in rodent models of PD...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903865/imaging-mitochondrial-dynamics-in-human-skin-reveals-depth-dependent-hypoxia-and-malignant-potential-for-diagnosis
#2
Dimitra Pouli, Mihaela Balu, Carlo A Alonzo, Zhiyi Liu, Kyle P Quinn, Francisca Rius-Diaz, Ronald M Harris, Kristen M Kelly, Bruce J Tromberg, Irene Georgakoudi
Active changes in mitochondrial structure and organization facilitate cellular homeostasis. Because aberrant mitochondrial dynamics are implicated in a variety of human diseases, their assessment is potentially useful for diagnosis, therapy, and disease monitoring. Because current techniques for evaluating mitochondrial morphology are invasive or necessitate mitochondria-specific dyes, their clinical translation is limited. We report that mitochondrial dynamics can be monitored in vivo, within intact human skin by relying entirely on endogenous two-photon-excited fluorescence from the reduced metabolic coenzyme nicotinamide adenine dinucleotide (NADH)...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903864/oral-thrombin-inhibitor-aggravates-platelet-adhesion-and-aggregation-during-arterial-thrombosis
#3
Tobias Petzold, Manuela Thienel, Ildiko Konrad, Irene Schubert, Ron Regenauer, Boj Hoppe, Michael Lorenz, Annekathrin Eckart, Sue Chandraratne, Carsten Lennerz, Christof Kolb, Daniel Braun, Janina Jamasbi, Richard Brandl, Siegmund Braun, Wolfgang Siess, Christian Schulz, Steffen Massberg
In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#4
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#5
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903861/muscling-out-gene-mutations
#6
Kathryn A Whitehead
No abstract text is available yet for this article.
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903860/grave-effects-of-a-specific-immune-therapy
#7
Daniel J Moore
No abstract text is available yet for this article.
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903859/imaging-serotonin-reuptake-in-the-living-brain
#8
Lawrence K Fung
No abstract text is available yet for this article.
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903858/taking-cancer-drug-screening-very-personally
#9
Cesar M Castro
No abstract text is available yet for this article.
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881826/a-soft-wearable-microfluidic-device-for-the-capture-storage-and-colorimetric-sensing-of-sweat
#10
Ahyeon Koh, Daeshik Kang, Yeguang Xue, Seungmin Lee, Rafal M Pielak, Jeonghyun Kim, Taehwan Hwang, Seunghwan Min, Anthony Banks, Philippe Bastien, Megan C Manco, Liang Wang, Kaitlyn R Ammann, Kyung-In Jang, Phillip Won, Seungyong Han, Roozbeh Ghaffari, Ungyu Paik, Marvin J Slepian, Guive Balooch, Yonggang Huang, John A Rogers
Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881825/effects-of-a-gut-pathobiont-in-a-gnotobiotic-mouse-model-of-childhood-undernutrition
#11
Vitas E Wagner, Neelendu Dey, Janaki Guruge, Ansel Hsiao, Philip P Ahern, Nicholas P Semenkovich, Laura V Blanton, Jiye Cheng, Nicholas Griffin, Thaddeus S Stappenbeck, Olga Ilkayeva, Christopher B Newgard, William Petri, Rashidul Haque, Tahmeed Ahmed, Jeffrey I Gordon
To model how interactions among enteropathogens and gut microbial community members contribute to undernutrition, we colonized gnotobiotic mice fed representative Bangladeshi diets with sequenced bacterial strains cultured from the fecal microbiota of two 24-month-old Bangladeshi children: one healthy and the other underweight. The undernourished donor's bacterial collection contained an enterotoxigenic Bacteroides fragilis strain (ETBF), whereas the healthy donor's bacterial collection contained two nontoxigenic strains of B...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881824/two-tissue-resident-progenitor-lineages-drive-distinct-phenotypes-of-heterotopic-ossification
#12
Devaveena Dey, Jana Bagarova, Sarah J Hatsell, Kelli A Armstrong, Lily Huang, Joerg Ermann, Ashley J Vonner, Yue Shen, Agustin H Mohedas, Arthur Lee, Elisabeth M W Eekhoff, Annelies van Schie, Marie B Demay, Charles Keller, Amy J Wagers, Aris N Economides, Paul B Yu
Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1(R206H) knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881823/nanobodies-that-block-gating-of-the-p2x7-ion-channel-ameliorate-inflammation
#13
Welbeck Danquah, Catherine Meyer-Schwesinger, Björn Rissiek, Carolina Pinto, Arnau Serracant-Prat, Miriam Amadi, Domenica Iacenda, Jan-Hendrik Knop, Anna Hammel, Philine Bergmann, Nicole Schwarz, Joana Assunção, Wendy Rotthier, Friedrich Haag, Eva Tolosa, Peter Bannas, Eric Boué-Grabot, Tim Magnus, Toon Laeremans, Catelijne Stortelers, Friedrich Koch-Nolte
Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β)...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881822/lowered-h3k27me3-and-dna-hypomethylation-define-poorly-prognostic-pediatric-posterior-fossa-ependymomas
#14
Jill Bayliss, Piali Mukherjee, Chao Lu, Siddhant U Jain, Chan Chung, Daniel Martinez, Benjamin Sabari, Ashley S Margol, Pooja Panwalkar, Abhijit Parolia, Melike Pekmezci, Richard C McEachin, Marcin Cieslik, Benita Tamrazi, Benjamin A Garcia, Gaspare La Rocca, Mariarita Santi, Peter W Lewis, Cynthia Hawkins, Ari Melnick, C David Allis, Craig B Thompson, Arul M Chinnaiyan, Alexander R Judkins, Sriram Venneti
Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881821/nih-s-transformative-opportunities-for-the-behavioral-and-social-sciences
#15
EDITORIAL
Francis S Collins, William T Riley
No abstract text is available yet for this article.
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881820/biomaterials-based-biologic-burst-release-builds-better-bone
#16
Bret D Ulery
No abstract text is available yet for this article.
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881819/sweet-signals-and-diabetes-carbohydrate-binding-proteins-contribute-to-insulin-resistance
#17
Sarah A Stanley
No abstract text is available yet for this article.
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881818/bugs-clogging-your-arteries-take-an-anti-b2-shot
#18
Purna Kashyap
No abstract text is available yet for this article.
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881817/photoacoustic-imaging-sounds-the-alarm-on-liver-fibrosis
#19
Conor L Evans
No abstract text is available yet for this article.
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27856799/reloadable-multidrug-capturing-delivery-system-for-targeted-ischemic-disease-treatment
#20
Jasmine P J Wu, Bill Cheng, Steve R Roffler, David J Lundy, Christopher Y T Yen, Peilin Chen, James J Lai, Suzie H Pun, Patrick S Stayton, Patrick C H Hsieh
Human clinical trials of protein therapy for ischemic diseases have shown disappointing outcomes so far, mainly because of the poor circulatory half-life of growth factors in circulation and their low uptake and retention by the targeted injury site. The attachment of polyethylene glycol (PEG) extends the circulatory half-lives of protein drugs but reduces their extravasation and retention at the target site. To address this issue, we have developed a drug capture system using a mixture of hyaluronic acid (HA) hydrogel and anti-PEG immunoglobulin M antibodies, which, when injected at a target body site, can capture and retain a variety of systemically injected PEGylated therapeutics at that site...
November 16, 2016: Science Translational Medicine
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