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Science Translational Medicine

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https://www.readbyqxmd.com/read/28724577/in-situ-expansion-of-engineered-human-liver-tissue-in-a-mouse-model-of-chronic-liver-disease
#1
Kelly R Stevens, Margaret A Scull, Vyas Ramanan, Chelsea L Fortin, Ritika R Chaturvedi, Kristin A Knouse, Jing W Xiao, Canny Fung, Teodelinda Mirabella, Amanda X Chen, Margaret G McCue, Michael T Yang, Heather E Fleming, Kwanghun Chung, Ype P de Jong, Christopher S Chen, Charles M Rice, Sangeeta N Bhatia
Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724576/erratum-for-the-research-article-neoadjuvant-chemotherapy-induces-breast-cancer-metastasis-through-a-tmem-mediated-mechanism-by-g-s-karagiannis-j-m-pastoriza-y-wang-a-s-harney-d-entenberg-j-pignatelli-v-p-sharma-e-a-xue-e-cheng-t-m-d-alfonso-j-g-jones-j-anampa
#2
https://www.readbyqxmd.com/read/28724575/a-multidirectional-gravity-assist-algorithm-that-enhances-locomotor-control-in-patients-with-stroke-or-spinal-cord-injury
#3
Jean-Baptiste Mignardot, Camille G Le Goff, Rubia van den Brand, Marco Capogrosso, Nicolas Fumeaux, Heike Vallery, Selin Anil, Jessica Lanini, Isabelle Fodor, Grégoire Eberle, Auke Ijspeert, Brigitte Schurch, Armin Curt, Stefano Carda, Jocelyne Bloch, Joachim von Zitzewitz, Grégoire Courtine
Gait recovery after neurological disorders requires remastering the interplay between body mechanics and gravitational forces. Despite the importance of gravity-dependent gait interactions and active participation for promoting this learning, these essential components of gait rehabilitation have received comparatively little attention. To address these issues, we developed an adaptive algorithm that personalizes multidirectional forces applied to the trunk based on patient-specific motor deficits. Implementation of this algorithm in a robotic interface reestablished gait dynamics during highly participative locomotion within a large and safe environment...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724574/the-microvascular-niche-instructs-t-cells-in-large-vessel-vasculitis-via-the-vegf-jagged1-notch-pathway
#4
Zhenke Wen, Yi Shen, Gerald Berry, Farhad Shahram, Yinyin Li, Ryu Watanabe, Yaping Joyce Liao, Jörg J Goronzy, Cornelia M Weyand
Microvascular networks in the adventitia of large arteries control access of inflammatory cells to the inner wall layers (media and intima) and thus protect the immune privilege of the aorta and its major branches. In autoimmune vasculitis giant cell arteritis (GCA), CD4 T helper 1 (TH1) and TH17 cells invade into the wall of the aorta and large elastic arteries to form tissue-destructive granulomas. Whether the disease microenvironment provides instructive cues for vasculitogenic T cells is unknown. We report that adventitial microvascular endothelial cells (mvECs) perform immunoregulatory functions by up-regulating the expression of the Notch ligand Jagged1...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#5
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701480/shining-new-light-on-migraine
#6
Maria K Lehtinen
Migraine-related photophobia is multifaceted and may be mediated by numerous pathways.
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701479/on-the-origin-of-relapse-in-aml
#7
Brian A Jonas
Preexisting therapy-resistant leukemia stem cell populations underlie the cellular origin of relapse in acute myeloid leukemia.
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701478/conjugation-does-not-conquer-all-in-cancer-nanotherapy
#8
Christopher Hine
Vaccination with potato virus X nanoparticles enhances the efficacy of traditional doxorubicin anticancer therapy against a mouse melanoma tumor model.
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701477/accelerating-the-production-of-insulating-brain-cells
#9
Kwanghun Chung
A 3D hydrogel enables rapid and scalable production of oligodendrocyte progenitor cells for transplantation to treat demyelination diseases.
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701476/detection-of-early-pancreatic-ductal-adenocarcinoma-with-thrombospondin-2-and-ca19-9-blood-markers
#10
Jungsun Kim, William R Bamlet, Ann L Oberg, Kari G Chaffee, Greg Donahue, Xing-Jun Cao, Suresh Chari, Benjamin A Garcia, Gloria M Petersen, Kenneth S Zaret
Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701475/hif-activation-causes-synthetic-lethality-between-the-vhl-tumor-suppressor-and-the-ezh1-histone-methyltransferase
#11
Abhishek A Chakraborty, Eijiro Nakamura, Jun Qi, Amanda Creech, Jacob D Jaffe, Joshiawa Paulk, Jesse S Novak, Kshithija Nagulapalli, Samuel K McBrayer, Glenn S Cowley, Javier Pineda, Jiaxi Song, Yaoyu E Wang, Steven A Carr, David E Root, Sabina Signoretti, James E Bradner, William G Kaelin
Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) is the signature lesion in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). pVHL loss causes the transcriptional activation of hypoxia-inducible factor (HIF) target genes, including many genes that encode histone lysine demethylases. Moreover, chromatin regulators are frequently mutated in this disease. We found that ccRCC displays increased H3K27 acetylation and a shift toward mono- or unmethylated H3K27 caused by an HIF-dependent increase in H3K27 demethylase activity...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701474/detecting-human-coronary-inflammation-by-imaging-perivascular-fat
#12
Alexios S Antonopoulos, Fabio Sanna, Nikant Sabharwal, Sheena Thomas, Evangelos K Oikonomou, Laura Herdman, Marios Margaritis, Cheerag Shirodaria, Anna-Maria Kampoli, Ioannis Akoumianakis, Mario Petrou, Rana Sayeed, George Krasopoulos, Constantinos Psarros, Patricia Ciccone, Carl M Brophy, Janet Digby, Andrew Kelion, Raman Uberoi, Suzan Anthony, Nikolaos Alexopoulos, Dimitris Tousoulis, Stephan Achenbach, Stefan Neubauer, Keith M Channon, Charalambos Antoniades
Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701473/zbtb7a-induction-in-alveolar-macrophages-is-implicated-in-anti-hla-mediated-lung-allograft-rejection
#13
Deepak K Nayak, Fangyu Zhou, Min Xu, Jing Huang, Moriya Tsuji, Jinsheng Yu, Ramsey Hachem, Andrew E Gelman, Ross M Bremner, Michael A Smith, Thalachallour Mohanakumar
Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679662/measuring-the-plasmodium-falciparum-hrp2-protein-in-blood-from-artesunate-treated-malaria-patients-predicts-post-artesunate-delayed-hemolysis
#14
Papa Alioune Ndour, Sébastien Larréché, Oussama Mouri, Nicolas Argy, Frédérick Gay, Camille Roussel, Stéphane Jauréguiberry, Claire Perillaud, Dominique Langui, Sylvestre Biligui, Nathalie Chartrel, Audrey Mérens, Eric Kendjo, Aniruddha Ghose, Md Mahtab Uddin Hassan, Md Amir Hossain, Hugh W F Kingston, Katherine Plewes, Arjen M Dondorp, Martin Danis, Sandrine Houzé, Serge Bonnefoy, Marc Thellier, Charles J Woodrow, Pierre A Buffet
Artesunate, the recommended drug for severe malaria, rapidly clears the malaria parasite from infected patients but frequently induces anemia-called post-artesunate delayed hemolysis (PADH)-for which a simple predictive test is urgently needed. The underlying event in PADH is the expulsion of artesunate-exposed parasites from their host erythrocytes by pitting. We show that the histidine-rich protein 2 (HRP2) of the malaria parasite Plasmodium falciparum persists in the circulation of artesunate-treated malaria patients in Bangladesh and in French travelers who became infected with malaria in Africa...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679661/glucose-regulated-protein-78-autoantibody-associates-with-blood-brain-barrier-disruption-in-neuromyelitis-optica
#15
Fumitaka Shimizu, Kristin L Schaller, Gregory P Owens, Anne C Cotleur, Debra Kellner, Yukio Takeshita, Birgit Obermeier, Thomas J Kryzer, Yasuteru Sano, Takashi Kanda, Vanda A Lennon, Richard M Ransohoff, Jeffrey L Bennett
Neuromyelitis optica (NMO) is an inflammatory disorder mediated by antibodies to aquaporin-4 (AQP4) with prominent blood-brain barrier (BBB) breakdown in the acute phase of the disease. Anti-AQP4 antibodies are produced mainly in the periphery, yet they target the astrocyte perivascular end feet behind the BBB. We reasoned that an endothelial cell-targeted autoantibody might promote BBB transit of AQP4 antibodies and facilitate NMO attacks. Using monoclonal recombinant antibodies (rAbs) from patients with NMO, we identified two that strongly bound to the brain microvascular endothelial cells (BMECs)...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679660/self-tanning-cells-the-new-spf
#16
Monica Venere
A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage.
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679659/enduring-scars-of-cocaine
#17
Vasiliki Michopoulos
Long-lasting metabolic changes within the brain upon abstinence from cocaine self-administration may increase risk for relapse.
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679658/defining-targets-to-defeat-hidradenitis-suppurativa
#18
Hadar Lev-Tov
Immunological data implicates IL-17 pathway in the pathogenesis of hidradenitis suppurativa.
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679657/eccentric-implants-stand-alone
#19
Christopher M Jewell
Controlling antibiotic drug clustering in replacement joint material provides a single-step strategy to clear infection while maintaining the mechanical strength needed for load bearing.
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28679656/staphylococcus-aureus-and-staphylococcus-epidermidis-strain-diversity-underlying-pediatric-atopic-dermatitis
#20
Allyson L Byrd, Clay Deming, Sara K B Cassidy, Oliver J Harrison, Weng-Ian Ng, Sean Conlan, Yasmine Belkaid, Julia A Segre, Heidi H Kong
The heterogeneous course, severity, and treatment responses among patients with atopic dermatitis (AD; eczema) highlight the complexity of this multifactorial disease. Prior studies have used traditional typing methods on cultivated isolates or sequenced a bacterial marker gene to study the skin microbial communities of AD patients. Shotgun metagenomic sequence analysis provides much greater resolution, elucidating multiple levels of microbial community assembly ranging from kingdom to species and strain-level diversification...
July 5, 2017: Science Translational Medicine
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