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  • Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Ling Gao, Lu Wang, Yuhua Wei, Prasanna Krishnamurthy, Gregory P. Walcott, Philippe Menasché, Jianyi Zhang

    Cell therapy treatment of myocardial infarction (MI) is mediated, in part, by exosomes secreted from transplanted cells. Thus, we compared the efficacy of treatment with a mixture of cardiomyocytes (CMs; 10 million), endothelial cells (ECs; 5 million), and smooth muscle cells (SMCs; 5 million) derived from human induced pluripotent stem cells (hiPSCs), or with exosomes extracted from the three cell

    更新日期:2020-09-16
  • Metabolic control of NLRP3 inflammasome by itaconation
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Jan Van den Bossche

    The Krebs cycle–derived immunometabolite itaconate constrains NLRP3 inflammasome activation and IL-1β release.

    更新日期:2020-09-16
  • Can eating help treat malaria?
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Jennifer M. Hurley

    The identification of metabolic control of the Plasmodium life cycle may open novel avenues for malaria treatment.

    更新日期:2020-09-16
  • Memory at the margins: Antipsychotic enhances the binding of fear memory with its context
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Jennifer Strafford Stevens

    A nontraditional antipsychotic medication enhances healthy memory function in a mouse model of fear conditioning.

    更新日期:2020-09-16
  • Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Sonia García-Calzón, Alexander Perfilyev, Mats Martinell, Monta Ustinova, Sebastian Kalamajski, Paul W. Franks, Karl Bacos, Ilze Elbere, Jussi Pihlajamäki, Petr Volkov, Allan Vaag, Leif Groop, Marlena Maziarz, Janis Klovins, Emma Ahlqvist, Charlotte Ling

    Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA

    更新日期:2020-09-16
  • ROR2 blockade as a therapy for osteoarthritis
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Anne-Sophie Thorup, Danielle Strachan, Sara Caxaria, Blandine Poulet, Bethan L. Thomas, Suzanne E. Eldridge, Giovanna Nalesso, James R. Whiteford, Costantino Pitzalis, Thomas Aigner, Roger Corder, Jessica Bertrand, Francesco Dell’Accio

    Osteoarthritis is characterized by the loss of the articular cartilage, bone remodeling, pain, and disability. No pharmacological intervention can currently halt progression of osteoarthritis. Here, we show that blocking receptor tyrosine kinase–like orphan receptor 2 (ROR2) improves cartilage integrity and pain in osteoarthritis models by inhibiting yes-associated protein (YAP) signaling. ROR2 was

    更新日期:2020-09-16
  • Interleukin-2 signals converge in a lymphoid–dendritic cell pathway that promotes anticancer immunity
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Miro E. Raeber, Rodney A. Rosalia, Dominic Schmid, Ufuk Karakus, Onur Boyman

    Tumor-infiltrating dendritic cells (DCs) correlate with effective anticancer immunity and improved responsiveness to anti–PD-1 checkpoint immunotherapy. However, the drivers of DC expansion and intratumoral accumulation are ill-defined. We found that interleukin-2 (IL-2) stimulated DC formation through innate and adaptive lymphoid cells in mice and humans, and this increase in DCs improved anticancer

    更新日期:2020-09-16
  • B cell acute lymphoblastic leukemia cells mediate RANK-RANKL–dependent bone destruction
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Sujeetha A. Rajakumar, Eniko Papp, Kathy K. Lee, Ildiko Grandal, Daniele Merico, Careesa C. Liu, Bedilu Allo, Lucia Zhang, Marc D. Grynpas, Mark D. Minden, Johann K. Hitzler, Cynthia J. Guidos, Jayne S. Danska

    Although most children survive B cell acute lymphoblastic leukemia (B-ALL), they frequently experience long-term, treatment-related health problems, including osteopenia and osteonecrosis. Because some children present with fractures at ALL diagnosis, we considered the possibility that leukemic B cells contribute directly to bone pathology. To identify potential mechanisms of B-ALL–driven bone destruction

    更新日期:2020-09-16
  • Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to the graft-versus-leukemia effect
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-16
    Pavan Bachireddy, Christina Ennis, Vinhkhang N. Nguyen, Satyen H. Gohil, Kendell Clement, Sachet A. Shukla, Juliet Forman, Nikolaos Barkas, Samuel Freeman, Natalie Bavli, Liudmila Elagina, Ignaty Leshchiner, Arman W. Mohammad, Nathan D. Mathewson, Derin B. Keskin, Laura Z. Rassenti, Thomas J. Kipps, Jennifer R. Brown, Gad Getz, Vincent T. Ho, Andreas Gnirke, Donna Neuberg, Robert J. Soiffer, Jerome

    Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with

    更新日期:2020-09-16
  • Interfering too soon: Type I interferons can dampen antiviral immunity
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Allison C. Billi

    Short-term blockade of type I interferons at the time of viral infection or vaccine administration enhances immunological memory.

    更新日期:2020-09-10
  • Leaky pipes: Tau and apoE implicated in blood-brain barrier dysfunction in Alzheimer disease
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Albert A. Davis

    Concentrations of tight junction proteins correlate with tau and apolipoprotein E in Alzheimer disease brain tissue independent of cerebral amyloid angiopathy.

    更新日期:2020-09-10
  • Targeting leukemia-specific mutations
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Christopher G. Kanakry

    T cells can recognize neoantigens derived from protein products of characteristic genetic fusions and thereby specifically target leukemia cells.

    更新日期:2020-09-10
  • Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Liangliang Wang, Yan Gao, Gao Zhang, Dan Li, Zhenda Wang, Jie Zhang, Leandro C. Hermida, Lei He, Zhisong Wang, Jingwen Si, Shuang Geng, Rizi Ai, Fei Ning, Chaoran Cheng, Haiteng Deng, Dimiter S. Dimitrov, Yan Sun, Yanyi Huang, Dong Wang, Xiaoyu Hu, Zhi Wei, Wei Wang, Xuebin Liao

    Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules

    更新日期:2020-09-10
  • Restoring the natural tropism of AAV2 vectors for human liver
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Marti Cabanes-Creus, Claus V. Hallwirth, Adrian Westhaus, Boaz H. Ng, Sophia H.Y. Liao, Erhua Zhu, Renina Gale Navarro, Grober Baltazar, Matthieu Drouyer, Suzanne Scott, Grant J. Logan, Giorgia Santilli, Antonette Bennett, Samantha L. Ginn, Geoff McCaughan, Adrian J. Thrasher, Mavis Agbandje-McKenna, Ian E. Alexander, Leszek Lisowski

    Recent clinical successes in gene therapy applications have intensified interest in using adeno-associated viruses (AAVs) as vectors for therapeutic gene delivery. Although prototypical AAV2 shows robust in vitro transduction of human hepatocyte–derived cell lines, it has not translated into an effective vector for liver-directed gene therapy in vivo. This is consistent with observations made in F

    更新日期:2020-09-10
  • A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson’s disease
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Ibrahim Boussaad, Carolin D. Obermaier, Zoé Hanss, Dheeraj R. Bobbili, Silvia Bolognin, Enrico Glaab, Katarzyna Wołyńska, Nicole Weisschuh, Laura De Conti, Caroline May, Florian Giesert, Dajana Grossmann, Annika Lambert, Susanne Kirchen, Maria Biryukov, Lena F. Burbulla, Francois Massart, Jill Bohler, Gérald Cruciani, Benjamin Schmid, Annerose Kurz-Drexler, Patrick May, Stefano Duga, Christine Klein

    Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of PARK7-linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial

    更新日期:2020-09-10
  • Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Antoine P. Fournier, Sara Martinez de Lizarrondo, Adrien Rateau, Axel Gerard-Brisou, Maximilian J. Waldner, Markus F. Neurath, Denis Vivien, Fabian Docagne, Maxime Gauberti

    Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ

    更新日期:2020-09-10
  • Characterization of ANGPT2 mutations associated with primary lymphedema
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Veli-Matti Leppänen, Pascal Brouillard, Emilia A. Korhonen, Tuomas Sipilä, Sawan Kumar Jha, Nicole Revencu, Veerle Labarque, Elodie Fastré, Matthieu Schlögel, Marie Ravoet, Amihood Singer, Claudia Luzzatto, Donatella Angelone, Giovanni Crichiutti, Angela D’Elia, Jaakko Kuurne, Harri Elamaa, Gou Young Koh, Pipsa Saharinen, Miikka Vikkula, Kari Alitalo

    Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain <30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via the TIE1-TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor–like

    更新日期:2020-09-10
  • Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-09
    Ian A. Myles, Carlo R. Castillo, Kent D. Barbian, Kishore Kanakabandi, Kimmo Virtaneva, Emily Fitzmeyer, Monica Paneru, Francisco Otaizo-Carrasquero, Timothy G. Myers, Tovah E. Markowitz, Ian N. Moore, Xue Liu, Marc Ferrer, Yosuke Sakamachi, Stavros Garantziotis, Muthulekha Swamydas, Michail S. Lionakis, Erik D. Anderson, Noah J. Earland, Sundar Ganesan, Ashleigh A. Sun, Jenna R.E. Bergerson, Robert

    Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium Roseomonas mucosa for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action

    更新日期:2020-09-10
  • We're on our own.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-04
    H Holden Thorp

    The failure of U.S. government scientists in the Trump administration to follow the science around COVID-19 has left the medical community to fend for itself.

    更新日期:2020-09-04
  • Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Anthony K Park,Yuman Fong,Sang-In Kim,Jason Yang,John P Murad,Jianming Lu,Brook Jeang,Wen-Chung Chang,Nanhai G Chen,Sandra H Thomas,Stephen J Forman,Saul J Priceman

    Chimeric antigen receptor (CAR)–engineered T cell therapy for solid tumors is limited by the lack of both tumor-restricted and homogeneously expressed tumor antigens. Therefore, we engineered an oncolytic virus to express a nonsignaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-CAR T cells. Infecting tumor cells with an oncolytic vaccinia virus coding

    更新日期:2020-09-03
  • A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Ludivine Grzelak,Sarah Temmam,Cyril Planchais,Caroline Demeret,Laura Tondeur,Christèle Huon,Florence Guivel-Benhassine,Isabelle Staropoli,Maxime Chazal,Jeremy Dufloo,Delphine Planas,Julian Buchrieser,Maaran Michael Rajah,Remy Robinot,Françoise Porrot,Mélanie Albert,Kuang-Yu Chen,Bernadette Crescenzo-Chaigne,Flora Donati,François Anna,Philippe Souque,Marion Gransagne,Jacques Bellalou,Mireille Nowakowski

    It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti–SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with

    更新日期:2020-09-03
  • C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Casey N Cook,Yanwei Wu,Hana M Odeh,Tania F Gendron,Karen Jansen-West,Giulia Del Rosso,Mei Yue,Peizhou Jiang,Edward Gomes,Jimei Tong,Lillian M Daughrity,Nicole M Avendano,Monica Castanedes-Casey,Wei Shao,Björn Oskarsson,Giulio S Tomassy,Alexander McCampbell,Frank Rigo,Dennis W Dickson,James Shorter,Yong-Jie Zhang,Leonard Petrucelli

    TAR DNA-binding protein 43 (TDP-43) inclusions are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), including cases caused by G4C2 repeat expansions in the C9orf72 gene (c9FTD/ALS). Providing mechanistic insight into the link between C9orf72 mutations and TDP-43 pathology, we demonstrated that a glycine-arginine repeat protein [poly(GR)] translated from

    更新日期:2020-09-03
  • Organoids control glucose
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Bence György

    Human islet-like organoids improve glucose control in immunocompetent mice.

    更新日期:2020-09-03
  • PARP inhibitors unleash the antitumor immune response
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Ecaterina Ileana-Dumbrava

    Combination of a PARP inhibitor with immune checkpoint blockade showed promising antitumor activity without additional toxicity.

    更新日期:2020-09-03
  • Shedding light on heart failure
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Ellen T. Roche

    Optogenetic stimulation of vagal preganglionic neurons preserved left ventricular ejection fraction in an experimental heart failure model.

    更新日期:2020-09-03
  • A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Monique B Nilsson,Huiying Sun,Jacqulyne Robichaux,Matthias Pfeifer,Ultan McDermott,Jon Travers,Lixia Diao,Yuanxin Xi,Pan Tong,Li Shen,Mia Hofstad,Masanori Kawakami,Xiuning Le,Xi Liu,Youhong Fan,Alissa Poteete,Limei Hu,Marcelo V Negrao,Hai Tran,Ethan Dmitrovsky,David Peng,Don L Gibbons,Jing Wang,John V Heymach

    Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which resistance emerges through EGFR-independent mechanisms, such as through pathways that promote epithelial-to-mesenchymal transition (EMT). Through an integrated transcriptomic, proteomic, and drug screening approach, we identified

    更新日期:2020-09-03
  • SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Magdalene K Montgomery,Jacqueline Bayliss,Camille Devereux,Ayenachew Bezawork-Geleta,David Roberts,Cheng Huang,Ralf B Schittenhelm,Andrew Ryan,Scott L Townley,Luke A Selth,Trevor J Biden,Gregory R Steinberg,Dorit Samocha-Bonet,Ruth C R Meex,Matthew J Watt

    Intertissue communication is a fundamental feature of metabolic regulation, and the liver is central to this process. We have identified sparc-related modular calcium-binding protein 1 (SMOC1) as a glucose-responsive hepatokine and regulator of glucose homeostasis. Acute intraperitoneal administration of SMOC1 improved glycemic control and insulin sensitivity in mice without changes in insulin secretion

    更新日期:2020-09-03
  • Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-09-02
    Suzanne E Eldridge,Aida Barawi,Hui Wang,Anke J Roelofs,Magdalena Kaneva,Zeyu Guan,Helen Lydon,Bethan L Thomas,Anne-Sophie Thorup,Beatriz F Fernandez,Sara Caxaria,Danielle Strachan,Ahmed Ali,Kanatheepan Shanmuganathan,Costantino Pitzalis,James R Whiteford,Frances Henson,Andrew W McCaskie,Cosimo De Bari,Francesco Dell'Accio

    Cartilage loss leads to osteoarthritis, the most common cause of disability for which there is no cure. Cartilage regeneration, therefore, is a priority in medicine. We report that agrin is a potent chondrogenic factor and that a single intraarticular administration of agrin induced long-lasting regeneration of critical-size osteochondral defects in mice, with restoration of tissue architecture and

    更新日期:2020-09-03
  • Gastrointestinal synthetic epithelial linings.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Junwei Li,Thomas Wang,Ameya R Kirtane,Yunhua Shi,Alexis Jones,Zaina Moussa,Aaron Lopes,Joy Collins,Siddartha M Tamang,Kaitlyn Hess,Rameen Shakur,Paramesh Karandikar,Jung Seung Lee,Hen-Wei Huang,Alison Hayward,Giovanni Traverso

    Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption and identified catalase

    更新日期:2020-08-27
  • BET inhibition increases βIII-tubulin expression and sensitizes metastatic breast cancer in the brain to vinorelbine.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Deepak Kanojia,Wojciech K Panek,Alex Cordero,Jawad Fares,Annie Xiao,Solomiia Savchuk,Krishan Kumar,Ting Xiao,Katarzyna C Pituch,Jason Miska,Peng Zhang,Kwok-Ling Kam,Craig Horbinski,Irina V Balyasnikova,Atique U Ahmed,Maciej S Lesniak

    Metastases from primary breast cancer result in poor survival. βIII-tubulin (TUBB3) has been established as a therapeutic target for breast cancer metastases specifically to the brain. In this study, we conducted a systematic analysis to determine the regulation of TUBB3 expression in breast cancer metastases to the brain and strategically target these metastases using vinorelbine (VRB), a drug approved

    更新日期:2020-08-27
  • Mapping cancer genetics at single-cell resolution.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Luke A Gilbert

    CRISPR genetic interaction mapping reveals networks of genes that drive cancer phenotypes.

    更新日期:2020-08-27
  • A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Emily J Davis,Lauren Broestl,Samira Abdulai-Saiku,Kurtresha Worden,Luke W Bonham,Elena Miñones-Moyano,Arturo J Moreno,Dan Wang,Kevin Chang,Gina Williams,Bayardo I Garay,Iryna Lobach,Nino Devidze,Daniel Kim,Cliff Anderson-Bergman,Gui-Qiu Yu,Charles C White,Julie A Harris,Bruce L Miller,David A Bennett,Arthur P Arnold,Phil L De Jager,Jorge J Palop,Barbara Panning,Jennifer S Yokoyama,Lennart Mucke,Dena

    A major sex difference in Alzheimer’s disease (AD) is that men with the disease die earlier than do women. In aging and preclinical AD, men also show more cognitive deficits. Here, we show that the X chromosome affects AD-related vulnerability in mice expressing the human amyloid precursor protein (hAPP), a model of AD. XY-hAPP mice genetically modified to develop testicles or ovaries showed worse

    更新日期:2020-08-27
  • Breaking up forces stem cells to come together
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Carlos A. Aguilar

    Microfracture surgery followed by local delivery of therapy induces stem cells to rebuild cartilage in osteoarthritis.

    更新日期:2020-08-27
  • Sirt2: A master regulator of T cell metabolism?
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Lewis Z. Shi

    Sirt2 controls metabolic fitness and antitumor function of T cells.

    更新日期:2020-08-27
  • Novel stem cell niche to preserve vision
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Su Xinyi

    Neural derived cells in the optic nerve express multiple stem cell markers and can differentiate into multiple neural lineages.

    更新日期:2020-08-27
  • Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Zhou Han,Chunling Chen,Anne Christiansen,Sophina Ji,Qian Lin,Charles Anumonwo,Chante Liu,Steven C Leiser,Meena,Isabel Aznarez,Gene Liau,Lori L Isom

    Dravet syndrome (DS) is an intractable developmental and epileptic encephalopathy caused largely by de novo variants in the SCN1A gene, resulting in haploinsufficiency of the voltage-gated sodium channel α subunit NaV1.1. Here, we used Targeted Augmentation of Nuclear Gene Output (TANGO) technology, which modulates naturally occurring, nonproductive splicing events to increase target gene and protein

    更新日期:2020-08-27
  • Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Xiayi Xu,Xianfeng Xia,Kunyu Zhang,Aliza Rai,Zhuo Li,Pengchao Zhao,Kongchang Wei,Li Zou,Boguang Yang,Wai-Ki Wong,Philip Wai-Yan Chiu,Liming Bian

    Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here

    更新日期:2020-08-27
  • CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-26
    Chih-Hao Wang,Morten Lundh,Accalia Fu,Rókus Kriszt,Tian Lian Huang,Matthew D Lynes,Luiz O Leiria,Farnaz Shamsi,Justin Darcy,Bennett P Greenwood,Niven R Narain,Vladimir Tolstikov,Kyle L Smith,Brice Emanuelli,Young-Tae Chang,Susan Hagen,Nika N Danial,Michael A Kiebish,Yu-Hua Tseng

    Brown and brown-like beige/brite adipocytes dissipate energy and have been proposed as therapeutic targets to combat metabolic disorders. However, the therapeutic effects of cell-based therapy in humans remain unclear. Here, we created human brown-like (HUMBLE) cells by engineering human white preadipocytes using CRISPR-Cas9–SAM–gRNA to activate endogenous uncoupling protein 1 expression. Obese mice

    更新日期:2020-08-27
  • De novo prediction of cancer-associated T cell receptors for noninvasive cancer detection.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Daria Beshnova,Jianfeng Ye,Oreoluwa Onabolu,Benjamin Moon,Wenxin Zheng,Yang-Xin Fu,James Brugarolas,Jayanthi Lea,Bo Li

    The adaptive immune system recognizes tumor antigens at an early stage to eradicate cancer cells. This process is accompanied by systemic proliferation of the tumor antigen–specific T lymphocytes. While detection of asymptomatic early-stage cancers is challenging due to small tumor size and limited somatic alterations, tracking peripheral T cell repertoire changes may provide an attractive solution

    更新日期:2020-08-20
  • Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Nicholas A J Dawson,Isaac Rosado-Sánchez,German E Novakovsky,Vivian C W Fung,Qing Huang,Emma McIver,Grace Sun,Jana Gillies,Madeleine Speck,Paul C Orban,Majid Mojibian,Megan K Levings

    Antigen-specific regulatory T cells (Tregs) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal Treg therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do Tregs. To date, most of the CAR Treg studies used second-generation

    更新日期:2020-08-20
  • Considering COVID-19 kidney injury
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Girish N. Nadkarni

    Does SARS-CoV-2 infection have long-term effects on the kidney?

    更新日期:2020-08-20
  • An affinity for pure drugs
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Christopher B. Rodell

    High-affinity supramolecular interactions improve the purification of recombinant therapeutic proteins, simplifying their production.

    更新日期:2020-08-20
  • It’s all about the X
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Priyathama Vellanki

    Genes expressed on the X chromosome affect body weight and body fat composition.

    更新日期:2020-08-20
  • 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Athri D Rathnayake,Jian Zheng,Yunjeong Kim,Krishani Dinali Perera,Samantha Mackin,David K Meyerholz,Maithri M Kashipathy,Kevin P Battaile,Scott Lovell,Stanley Perlman,William C Groutas,Kyeong-Ok Chang

    Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like

    更新日期:2020-08-20
  • Artery to vein configuration of arteriovenous fistula improves hemodynamics to increase maturation and patency.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Hualong Bai,Nirvana Sadaghianloo,Jolanta Gorecka,Shirley Liu,Shun Ono,Abhay B Ramachandra,Sophie Bonnet,Nathalie M Mazure,Serge Declemy,Jay D Humphrey,Alan Dardik

    Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, but 60% of conventional [vein-to-artery (V-A)] AVF fail to mature, and only 50% remain patent at 1 year. We previously showed improved maturation and patency in a pilot study of the radial artery deviation and reimplantation (RADAR) technique that uses an artery-to-vein (A-V) configuration. Here, we show that RADAR exhibits

    更新日期:2020-08-20
  • Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Sarah Alsamman, Stephanie A. Christenson, Amy Yu, Nadia M. E. Ayad, Meghan S. Mooring, Joe M. Segal, Jimmy Kuang-Hsien Hu, Johanna R. Schaub, Steve S. Ho, Vikram Rao, Megan M. Marlow, Scott M. Turner, Mai Sedki, Lorena Pantano, Sarani Ghoshal, Diego Dos Santos Ferreira, Hsiao-Yen Ma, Caroline C. Duwaerts, Regina Espanol-Suner, Lan Wei, Benjamin Newcomb, Izolda Mileva, Daniel Canals, Yusuf A. Hannun

    Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits

    更新日期:2020-08-20
  • Pathophysiological regulation of lung function by the free fatty acid receptor FFA4.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-19
    Rudi Prihandoko,Davinder Kaur,Coen H Wiegman,Elisa Alvarez-Curto,Chantal Donovan,Latifa Chachi,Trond Ulven,Martha R Tyas,Eloise Euston,Zhaoyang Dong,Abdulrahman Ghali M Alharbi,Richard Y Kim,Jack G Lowe,Philip M Hansbro,Kian Fan Chung,Christopher E Brightling,Graeme Milligan,Andrew B Tobin

    Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein–coupled receptor family, FFA4, that responds to free circulating fatty acids including

    更新日期:2020-08-20
  • These nanoparticles are just right
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    James Ankrum

    Optimizing nanoparticle size, charge, and route of delivery enables highly efficient and selective targeting of tumor-associated macrophages.

    更新日期:2020-08-14
  • Genetic ultrasonic biosensor for picturing proteases
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Raag Airan

    A genetically encoded biosensor allows noninvasive imaging of protease activity using ultrasound.

    更新日期:2020-08-14
  • A gut feeling to stress enhances neutrophil-mediated vascular occlusion
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Chiara Giannarelli

    Psychological stress alters TH17 cell response to gut microbiome and triggers acute vascular-occlusion induced by aged-neutrophils in sickle cell disease.

    更新日期:2020-08-14
  • Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Xueguang Lu,Lei Miao,Wenting Gao,Ziqi Chen,Kevin J McHugh,Yehui Sun,Zachary Tochka,Stephanie Tomasic,Kaitlyn Sadtler,Alain Hyacinthe,Yuxuan Huang,Tyler Graf,Quanyin Hu,Morteza Sarmadi,Robert Langer,Daniel G Anderson,Ana Jaklenec

    Activation of the stimulator of interferon gene (STING) pathway within the tumor microenvironment has been shown to generate a strong antitumor response. Although local administration of STING agonists has promise for cancer immunotherapy, the dosing regimen needed to achieve efficacy requires frequent intratumoral injections over months. Frequent dosing for cancer treatment is associated with poor

    更新日期:2020-08-14
  • Predicting functional effects of missense variants in voltage-gated sodium and calcium channels.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Henrike O Heyne,David Baez-Nieto,Sumaiya Iqbal,Duncan S Palmer,Andreas Brunklaus,Patrick May,,Katrine M Johannesen,Stephan Lauxmann,Johannes R Lemke,Rikke S Møller,Eduardo Pérez-Palma,Ute I Scholl,Steffen Syrbe,Holger Lerche,Dennis Lal,Arthur J Campbell,Hao-Ran Wang,Jen Pan,Mark J Daly

    Malfunctions of voltage-gated sodium and calcium channels (encoded by SCNxA and CACNA1x family genes, respectively) have been associated with severe neurologic, psychiatric, cardiac, and other diseases. Altered channel activity is frequently grouped into gain or loss of ion channel function (GOF or LOF, respectively) that often corresponds not only to clinical disease manifestations but also to differences

    更新日期:2020-08-14
  • A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Viet Loan Dao Thi,Konrad Herbst,Kathleen Boerner,Matthias Meurer,Lukas Pm Kremer,Daniel Kirrmaier,Andrew Freistaedter,Dimitrios Papagiannidis,Carla Galmozzi,Megan L Stanifer,Steeve Boulant,Steffen Klein,Petr Chlanda,Dina Khalid,Isabel Barreto Miranda,Paul Schnitzler,Hans-Georg Kräusslich,Michael Knop,Simon Anders

    The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) coronavirus is a major public health challenge. Rapid tests for detecting existing SARS-CoV-2 infections and assessing virus spread are critical. Approaches to detect viral RNA based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) have potential as simple

    更新日期:2020-08-14
  • Reelin depletion protects against autoimmune encephalomyelitis by decreasing vascular adhesion of leukocytes.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Laurent Calvier,Guillaume Demuth,Navid Manouchehri,Connie Wong,Anastasia Sacharidou,Chieko Mineo,Philip W Shaul,Nancy L Monson,Maria Z Kounnas,Olaf Stüve,Joachim Herz

    Neuroinflammation as a result of immune cell recruitment into the central nervous system (CNS) is a key pathogenic mechanism of multiple sclerosis (MS). However, current anti-inflammatory interventions depleting immune cells or directly targeting their trafficking into the CNS can have serious side effects, highlighting a need for better immunomodulatory strategies. We detected increased Reelin concentrations

    更新日期:2020-08-14
  • Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Yannouck F van Lier,Mark Davids,Nienke J E Haverkate,Pieter F de Groot,Marjolein L Donker,Ellen Meijer,Floor C J I Heubel-Moenen,Erfan Nur,Sacha S Zeerleder,Max Nieuwdorp,Bianca Blom,Mette D Hazenberg

    Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset

    更新日期:2020-08-14
  • Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-12
    Shanna L Ashley,Michael W Sjoding,Antonia P Popova,Tracy X Cui,Matthew J Hoostal,Thomas M Schmidt,William R Branton,Michael G Dieterle,Nicole R Falkowski,Jennifer M Baker,Kevin J Hinkle,Kristine E Konopka,John R Erb-Downward,Gary B Huffnagle,Robert P Dickson

    Inhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species (e.g.,

    更新日期:2020-08-14
  • Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche.
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-05
    Zhiping Liu,Jiean Xu,Qian Ma,Xiaoyu Zhang,Qiuhua Yang,Lina Wang,Yapeng Cao,Zhimin Xu,Amany Tawfik,Ye Sun,Neal L Weintraub,David J Fulton,Mei Hong,Zheng Dong,Lois E H Smith,Ruth B Caldwell,Akrit Sodhi,Yuqing Huo

    The coordination of metabolic signals among different cellular components in pathological retinal angiogenesis is poorly understood. Here, we showed that in the pathological angiogenic vascular niche, retinal myeloid cells, particularly macrophages/microglia that are spatially adjacent to endothelial cells (ECs), are highly glycolytic. We refer to these macrophages/microglia that exhibit a unique angiogenic

    更新日期:2020-08-06
  • Confetti illuminates the cryptic way calorie restriction protects from cancer
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-05
    Emily J. Gallagher

    Calorie restriction increases intestinal stem cell competition and decreases the retention of stem cells with mutations in mice.

    更新日期:2020-08-06
  • Chrono-immunization with BCG: It is about “time”!
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-05
    Shaon Sengupta

    Morning vaccination with BCG enhances immunity.

    更新日期:2020-08-06
  • Not all fibroblasts are equal in cancer
    Sci. Transl. Med. (IF 16.304) Pub Date : 2020-08-05
    Ioannis Zervantonakis

    The ratio of two cancer-associated fibroblast subpopulations with distinct functions affects breast cancer clinical outcomes.

    更新日期:2020-08-06
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