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  • Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Jesse D. Kirkpatrick, Andrew D. Warren, Ava P. Soleimany, Peter M. K. Westcott, Justin C. Voog, Carmen Martin-Alonso, Heather E. Fleming, Tuomas Tammela, Tyler Jacks, Sangeeta N. Bhatia

    Lung cancer is the leading cause of cancer-related death, and patients most commonly present with incurable advanced-stage disease. U.S. national guidelines recommend screening for high-risk patients with low-dose computed tomography, but this approach has limitations including high false-positive rates. Activity-based nanosensors can detect dysregulated proteases in vivo and release a reporter to

    更新日期:2020-04-01
  • PBX1 expression in uterine natural killer cells drives fetal growth
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Yonggang Zhou, Binqing Fu, Xiuxiu Xu, Jinghe Zhang, Xianhong Tong, Yanshi Wang, Zhongjun Dong, Xiaoren Zhang, Nan Shen, Yiwen Zhai, Xiangdong Kong, Rui Sun, Zhigang Tian, Haiming Wei

    Abundant decidual natural killer (dNK) cells at the maternal-fetal interface are important during early pregnancy. However, functional subsets of dNK cells remain poorly understood. We describe a CD49a+PBX homeobox 1 (PBX1)+ dNK cell subset that promotes fetal development in humans and mice. The expression of PBX1 in dNK cells is up-regulated via the activated AKT1 pathway through the interaction of

    更新日期:2020-04-01
  • Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Sumit K. Subudhi, Luis Vence, Hao Zhao, Jorge Blando, Shalini S. Yadav, Qing Xiong, Alexandre Reuben, Ana Aparicio, Paul G. Corn, Brian F. Chapin, Louis L. Pisters, Patricia Troncoso, Rebecca Slack Tidwell, Peter Thall, Chang-Jiun Wu, Jianhua Zhang, Christopher L. Logothetis, Andrew Futreal, James P. Allison, Padmanee Sharma

    Tumors with high mutational burden (TMB) tend to be responsive to immune checkpoint blockade (ICB) because there are neoantigens available for targeting by reinvigorated T cells, whereas those with low TMB demonstrate limited clinical responses. To determine whether antigen-specific T cell responses can be elicited after treatment with ICB in cancers that have a low TMB, we conducted a clinical trial

    更新日期:2020-04-01
  • The neural circuit model in psychiatry pays off
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Jennifer Strafford Stevens

    Noninvasive brain stimulation in depressed patients can be used to target different neural circuits, improving different symptoms.

    更新日期:2020-04-01
  • Macrophages make you stronger
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Jan Van den Bossche

    Macrophage-derived meteorin-like promotes skeletal muscle repair.

    更新日期:2020-04-01
  • Spontaneous reversal of stenosis in tissue-engineered vascular grafts
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Joseph D. Drews, Victoria K. Pepper, Cameron A. Best, Jason M. Szafron, John P. Cheatham, Andrew R. Yates, Kan N. Hor, Jacob C. Zbinden, Yu-Chun Chang, Gabriel J. M. Mirhaidari, Abhay B. Ramachandra, Shinka Miyamoto, Kevin M. Blum, Ekene A. Onwuka, Jason Zakko, John Kelly, Sharon L. Cheatham, Nakesha King, James W. Reinhardt, Tadahisa Sugiura, Hideki Miyachi, Yuichi Matsuzaki, Julie Breuer, Eric D

    We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)–approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first

    更新日期:2020-04-01
  • A durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Wen-Hsuan W. Lin, Eileen Moran, Robert J. Adams, Robert E. Sievers, Debra Hauer, Steven Godin, Diane E. Griffin

    Infection with wild-type (WT) measles virus (MeV) is an important cause of childhood mortality that leads to lifelong protective immunity in survivors. WT MeV and the live-attenuated MeV used in the measles vaccine (LAMV) are antigenically similar, but the determinants of attenuation are unknown, and protective immunity induced by LAMV is less robust than that induced by WT MeV. To identify factors

    更新日期:2020-04-01
  • Location, location, location: A tubal neighborhood unfriendly to implantation
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Ramakrishna Kommagani

    Reduced adrenomedullin secretion by tubal epithelial cells results in increased macrophage function and increased susceptibility to ectopic pregnancy.

    更新日期:2020-04-01
  • Control of brain tumor growth by reactivating myeloid cells with niacin
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-04-01
    Susobhan Sarkar, Runze Yang, Reza Mirzaei, Khalil Rawji, Candice Poon, Manoj K. Mishra, Franz J. Zemp, Pinaki Bose, John Kelly, Jeff F. Dunn, V. Wee Yong

    Glioblastomas are generally incurable partly because monocytes, macrophages, and microglia in afflicted patients do not function in an antitumor capacity. Medications that reactivate these macrophages/microglia, as well as circulating monocytes that become macrophages, could thus be useful to treat glioblastoma. We have discovered that niacin (vitamin B3) is a potential stimulator of these inefficient

    更新日期:2020-04-01
  • Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Angela Lek, Yuanfan Zhang, Keryn G. Woodman, Shushu Huang, Alec M. DeSimone, Justin Cohen, Vincent Ho, James Conner, Lillian Mead, Andrew Kodani, Anna Pakula, Neville Sanjana, Oliver D. King, Peter L. Jones, Kathryn R. Wagner, Monkol Lek, Louis M. Kunkel

    The emergence of CRISPR-Cas9 gene-editing technologies and genome-wide CRISPR-Cas9 libraries enables efficient unbiased genetic screening that can accelerate the process of therapeutic discovery for genetic disorders. Here, we demonstrate the utility of a genome-wide CRISPR-Cas9 loss-of-function library to identify therapeutic targets for facioscapulohumeral muscular dystrophy (FSHD), a genetically

    更新日期:2020-03-26
  • Out of the frying pan into the fire: IFN-γ in post-sepsis immunosuppression
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Allison C. Billi

    Secretion of IFN-γ in sepsis contributes to post-sepsis immunosuppression and secondary candidemia.

    更新日期:2020-03-26
  • Beyond synuclein: Organelle accumulation in Lewy bodies may drive neurodegeneration
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Albert A. Davis

    Organelle sequestration in Lewy bodies correlates more closely with neurodegeneration than α-synuclein aggregation alone.

    更新日期:2020-03-26
  • Wireless monitoring in the ICU
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Christopher G. Kanakry

    Monitoring of critically ill children can be improved by a soft, flexible wireless device that generates accurate, comprehensive, and continuous data.

    更新日期:2020-03-26
  • An ocular glymphatic clearance system removes β-amyloid from the rodent eye
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Xiaowei Wang, Nanhong Lou, Allison Eberhardt, Yujia Yang, Peter Kusk, Qiwu Xu, Benjamin Förstera, Sisi Peng, Meng Shi, Antonio Ladrón-de-Guevara, Christine Delle, Björn Sigurdsson, Anna L. R. Xavier, Ali Ertürk, Richard T. Libby, Lu Chen, Alexander S. Thrane, Maiken Nedergaard

    Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified an ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve in rodents. β-amyloid (Aβ) was cleared from the retina and vitreous via a pathway dependent on glial water channel aquaporin-4 (AQP4) and driven by the ocular-cranial pressure difference. After

    更新日期:2020-03-26
  • A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Katarzyna Jobin, Natascha E. Stumpf, Sebastian Schwab, Melanie Eichler, Patrick Neubert, Manfred Rauh, Marek Adamowski, Olena Babyak, Daniel Hinze, Sugirthan Sivalingam, Christina Weisheit, Katharina Hochheiser, Susanne Schmidt, Mirjam Meissner, Natalio Garbi, Zeinab Abdullah, Ulrich Wenzel, Michael Hölzel, Jonathan Jantsch, Christian Kurts

    The Western diet is rich in salt, which poses various health risks. A high-salt diet (HSD) can stimulate immunity through the nuclear factor of activated T cells 5 (Nfat5)–signaling pathway, especially in the skin, where sodium is stored. The kidney medulla also accumulates sodium to build an osmotic gradient for water conservation. Here, we studied the effect of an HSD on the immune defense against

    更新日期:2020-03-26
  • Quarterly picks from the editors
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    American Association for the Advancement of Science

    Four times a year, the Science Translational Medicine editors select recently published articles across the Science family of journals and highlight interesting translational ties. These short write-ups identify common links between disparate diseases; technologies and research approaches that could prove complementary; and biomedical insights that may inform therapies or treatments. This quarter’s

    更新日期:2020-03-26
  • Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Anna Julie Peired, Giulia Antonelli, Maria Lucia Angelotti, Marco Allinovi, Francesco Guzzi, Alessandro Sisti, Roberto Semeraro, Carolina Conte, Benedetta Mazzinghi, Sara Nardi, Maria Elena Melica, Letizia De Chiara, Elena Lazzeri, Laura Lasagni, Tiziano Lottini, Samuela Landini, Sabrina Giglio, Andrea Mari, Fabrizio Di Maida, Alessandro Antonelli, Francesco Porpiglia, Riccardo Schiavina, Vincenzo

    Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center

    更新日期:2020-03-26
  • Noninvasive localization of cardiac arrhythmias using electromechanical wave imaging
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Christopher S. Grubb, Lea Melki, Daniel Y. Wang, James Peacock, Jose Dizon, Vivek Iyer, Carmine Sorbera, Angelo Biviano, David A. Rubin, John P. Morrow, Deepak Saluja, Andrew Tieu, Pierre Nauleau, Rachel Weber, Salma Chaudhary, Irfan Khurram, Marc Waase, Hasan Garan, Elisa E. Konofagou, Elaine Y. Wan

    Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. The 12-lead electrocardiogram (ECG) is the current noninvasive clinical tool used to diagnose and localize cardiac arrhythmias. However, it has limited accuracy and is subject to operator bias. Here, we present electromechanical wave imaging (EWI), a high–frame rate ultrasound technique that can noninvasively map with high

    更新日期:2020-03-26
  • Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-25
    Constance J. Martin, Abhishek Datta, Christopher Littlefield, Ashish Kalra, Christopher Chapron, Stefan Wawersik, Kevin B. Dagbay, Christopher T. Brueckner, Anastasia Nikiforov, Francis T. Danehy, Frederick C. Streich, Christopher Boston, Allison Simpson, Justin W. Jackson, Susan Lin, Nicole Danek, Ryan R. Faucette, Pichai Raman, Allan D. Capili, Alan Buckler, Gregory J. Carven, Thomas Schürpf

    Despite breakthroughs achieved with cancer checkpoint blockade therapy (CBT), many patients do not respond to anti–programmed cell death-1 (PD-1) due to primary or acquired resistance. Human tumor profiling and preclinical studies in tumor models have recently uncovered transforming growth factor–β (TGFβ) signaling activity as a potential point of intervention to overcome primary resistance to CBT

    更新日期:2020-03-26
  • A quantitative super-resolution imaging toolbox for diagnosis of motile ciliopathies
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Zhen Liu, Quynh P. H. Nguyen, Qingxu Guan, Alexandra Albulescu, Lauren Erdman, Yasaman Mahdaviyeh, Jasmine Kang, Hong Ouyang, Richard G. Hegele, Theo Moraes, Anna Goldenberg, Sharon D. Dell, Vito Mennella

    Airway clearance of pathogens and particulates relies on motile cilia. Impaired cilia motility can lead to reduction in lung function, lung transplant, or death in some cases. More than 50 proteins regulating cilia motility are linked to primary ciliary dyskinesia (PCD), a heterogeneous, mainly recessive genetic lung disease. Accurate PCD molecular diagnosis is essential for identifying therapeutic

    更新日期:2020-03-19
  • Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Ana Maria Manso, Sherin I. Hashem, Bradley C. Nelson, Emily Gault, Angel Soto-Hermida, Elizza Villarruel, Michela Brambatti, Julius Bogomolovas, Paul J. Bushway, Chao Chen, Pavan Battiprolu, Annahita Keravala, Jonathan D. Schwartz, Gaurav Shah, Yusu Gu, Nancy D. Dalton, Kirk Hammond, Kirk Peterson, Paul Saftig, Eric D. Adler

    Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy associated with multiorgan dysfunction, including the heart, skeletal muscle, and liver. There are no specific treatments, and most male patients die from advanced heart failure during the second or third decade of life. DD is caused by mutations in the lysosomal-associated membrane protein 2 (LAMP2) gene, a key mediator of autophagy

    更新日期:2020-03-19
  • Priorities for developing respiratory syncytial virus vaccines in different target populations
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Simon B. Drysdale, Rachael S. Barr, Christine S. Rollier, Christopher A. Green, Andrew J. Pollard, Charles J. Sande

    The development of an effective vaccine against respiratory syncytial virus (RSV) has been hampered by major difficulties that occurred in the 1960s when a formalin-inactivated vaccine led to increased severity of RSV disease after acquisition of the virus in the RSV season after vaccination. Recent renewed efforts to develop a vaccine have resulted in about 38 candidate vaccines and monoclonal antibodies

    更新日期:2020-03-19
  • A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Joshua Y. C. Yang, Reuben D. Sarwal, Tara K. Sigdel, Izabella Damm, Ben Rosenbaum, Juliane M. Liberto, Chitranon Chan-On, José M. Arreola-Guerra, Josefina Alberu, Flavio Vincenti, Minnie M. Sarwal

    Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection of acute rejection (AR) and to affect the long-term survival of the transplant. We present the development and validation of a noninvasive, spot urine–based diagnostic assay based on measurements of six urinary DNA, protein, and metabolic biomarkers. The performance of this assay for detecting kidney

    更新日期:2020-03-19
  • Hope on the horizon for inherited blindness
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Bence György

    In a clinical trial, gene therapy for X-linked retinitis pigmentosa improved vision.

    更新日期:2020-03-19
  • Boosting immune responses against early breast cancer
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Ecaterina Ileana-Dumbrava

    Pembrolizumab combined with neoadjuvant chemotherapy improves therapeutic responses in patients with early triple-negative breast cancer.

    更新日期:2020-03-19
  • Not “dust” any neural stimulator
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Ellen Roche

    An untethered, ultrasound-powered milliscale device can stimulate peripheral nerves in rats.

    更新日期:2020-03-19
  • Platelets from HIV-infected individuals on antiretroviral drug therapy with poor CD4+ T cell recovery can harbor replication-competent HIV despite viral suppression
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Fernando Real, Claude Capron, Alexis Sennepin, Riccardo Arrigucci, Aiwei Zhu, Gérémy Sannier, Jonathan Zheng, Lin Xu, Jean-Marc Massé, Ségolène Greffe, Michelle Cazabat, Maribel Donoso, Pierre Delobel, Jacques Izopet, Eliseo Eugenin, Maria Laura Gennaro, Elisabeth Rouveix, Elisabeth Cramer Bordé, Morgane Bomsel

    In addition to hemostasis, human platelets have several immune functions and interact with infectious pathogens including HIV in vitro. Here, we report that platelets from HIV-infected individuals on combined antiretroviral drug therapy (ART) with low blood CD4+ T cell counts (<350 cells/μl) contained replication-competent HIV despite viral suppression. In vitro, human platelets harboring HIV propagated

    更新日期:2020-03-19
  • Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Katelyn Arnold, Yongmei Xu, Erica M. Sparkenbaugh, Miaomiao Li, Xiaorui Han, Xing Zhang, Ke Xia, Mark Piegore, Fuming Zhang, Xiaoxiao Zhang, Mike Henderson, Vijayakanth Pagadala, Guowei Su, Lisi Tan, Pyong Woo Park, Richard T. Stravitz, Nigel S. Key, Robert J. Linhardt, Rafal Pawlinski, Ding Xu, Jian Liu

    Acetaminophen/paracetamol (APAP) overdose is the leading cause of drug-induced acute liver failure (ALF) in the United States and Europe. The progression of the disease is attributed to sterile inflammation induced by the release of high mobility group box 1 (HMGB1) and the interaction with receptor for advanced glycation end products (RAGE). A specific, effective, and safe approach to neutralize the

    更新日期:2020-03-19
  • Strong vaccine responses during chemotherapy are associated with prolonged cancer survival
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-18
    Cornelis J. M. Melief, Marij J. P. Welters, Ignace Vergote, Judith R. Kroep, Gemma G. Kenter, Petronella B. Ottevanger, Wiebren A. A. Tjalma, Hannelore Denys, Mariette I. E. van Poelgeest, Hans W. Nijman, Anna K. L. Reyners, Thierry Velu, Frederic Goffin, Roy I. Lalisang, Nikki M. Loof, Sanne Boekestijn, Willem Jan Krebber, Leon Hooftman, Sonja Visscher, Brent A. Blumenstein, Richard B. Stead, Winald

    Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)–induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high

    更新日期:2020-03-19
  • Interdomain spacing and spatial configuration drive the potency of IgG-[L]-scFv T cell bispecific antibodies
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Brian H. Santich, Jeong A. Park, Hoa Tran, Hong-Fen Guo, Morgan Huse, Nai-Kong V. Cheung

    T cell–bispecific antibodies (BsAbs) couple cytotoxic T lymphocytes to tumor cells, inducing their destruction. Although there are more than 60 classes of BsAbs in development, the relative importance of parameters such as interdomain spacing or spatial configuration is largely unknown. Here, we dissected a symmetric dual bivalent BsAb platform (IgG-[L]-scFv: antitumor IgG with anti-CD3 scFv fused

    更新日期:2020-03-12
  • New coronavirus outbreak: Framing questions for pandemic prevention
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Scott P. Layne, James M. Hyman, David M. Morens, Jeffery K. Taubenberger

    We need to understand and quantify the dominant variables that govern the SARS–CoV-2 outbreak, rather than relying exclusively on confirmed cases and their geospatial spread.

    更新日期:2020-03-12
  • Combined nucleus pulposus augmentation and annulus fibrosus repair prevents acute intervertebral disc degeneration after discectomy
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Stephen R. Sloan, Christoph Wipplinger, Sertaç Kirnaz, Rodrigo Navarro-Ramirez, Franziska Schmidt, Duncan McCloskey, Tania Pannellini, Antonella Schiavinato, Roger Härtl, Lawrence J. Bonassar

    Tissue-engineered approaches for the treatment of early-stage intervertebral disc degeneration have shown promise in preclinical studies. However, none of these therapies has been approved for clinical use, in part because each therapy targets only one aspect of the intervertebral disc’s composite structure. At present, there is no reliable method to prevent intervertebral disc degeneration after herniation

    更新日期:2020-03-12
  • Hematopoietic maladaptation facilitates septic screening
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Carlos A. Aguilar

    Single-cell RNA sequencing of peripheral blood cells from patients with bacterial infections reveals a monocyte subset that can distinguish those at risk of sepsis.

    更新日期:2020-03-12
  • Trimming the “fatty” intratumoral Tregs for cancer immunotherapy
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Lewis Z. Shi

    Fatty acid receptor CD36 preferentially regulates intratumoral but not peripheral Tregs.

    更新日期:2020-03-12
  • “You are what you eat!”
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Xinyi Su

    Single-cell transcriptomic analysis reveals how caloric restriction prevents aging at the cellular level.

    更新日期:2020-03-12
  • Neurophysiological signatures in Alzheimer’s disease are distinctly associated with TAU, amyloid-β accumulation, and cognitive decline
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Kamalini G. Ranasinghe, Jungho Cha, Leonardo Iaccarino, Leighton B. Hinkley, Alexander J. Beagle, Julie Pham, William J. Jagust, Bruce L. Miller, Katherine P. Rankin, Gil D. Rabinovici, Keith A. Vossel, Srikantan S. Nagarajan

    Neural synchrony is intricately balanced in the normal resting brain but becomes altered in Alzheimer’s disease (AD). To determine the neurophysiological manifestations associated with molecular biomarkers of AD neuropathology, in patients with AD, we used magnetoencephalographic imaging (MEGI) and positron emission tomography with amyloid-beta (Aβ) and TAU tracers. We found that alpha oscillations

    更新日期:2020-03-12
  • An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Mohammad Mahdi Hasani-Sadrabadi, Patricia Sarrion, Sevda Pouraghaei, Yee Chau, Sahar Ansari, Song Li, Tara Aghaloo, Alireza Moshaverinia

    Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties. The engineered

    更新日期:2020-03-12
  • Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Maud Mayoux, Andreas Roller, Vesna Pulko, Stefano Sammicheli, Stanford Chen, Eva Sum, Christian Jost, Marieke F. Fransen, Regula B. Buser, Marcin Kowanetz, Karolin Rommel, Ines Matos, Sara Colombetti, Anton Belousov, Vaios Karanikas, Ferry Ossendorp, Priti S. Hegde, Daniel S. Chen, Pablo Umana, Mario Perro, Christian Klein, Wei Xu

    PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target

    更新日期:2020-03-12
  • Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-11
    Johanna M. Schafer, Brian D. Lehmann, Paula I. Gonzalez-Ericsson, Clayton B. Marshall, J. Scott Beeler, Lindsay N. Redman, Hailing Jin, Violeta Sanchez, Matthew C. Stubbs, Peggy Scherle, Kimberly N. Johnson, Quanhu Sheng, Joseph T. Roland, Joshua A. Bauer, Yu Shyr, Bapsi Chakravarthy, Bret C. Mobley, Scott W. Hiebert, Justin M. Balko, Melinda E. Sanders, Phillip C. C. Liu, Jennifer A. Pietenpol

    Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to endocrine therapy or human epidermal growth factor receptor 2 (HER2)–targeted therapies. Individuals with TNBC experience higher rates of relapse and shorter overall survival compared to patients with receptor-positive breast cancer subtypes. Preclinical discoveries are needed to identify, develop,

    更新日期:2020-03-12
  • Knowing what’s growing: Why ductal and intraductal prostate cancer matter
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Mitchell G. Lawrence, Laura H. Porter, David Clouston, Declan G. Murphy, Mark Frydenberg, Renea A. Taylor, Gail P. Risbridger

    Prostate cancer is a common malignancy, but only some tumors are lethal. Accurately identifying these tumors will improve clinical practice and instruct research. Aggressive cancers often have distinctive pathologies, including intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma. Here, we review the importance of these pathologies because they are often overlooked, especially in

    更新日期:2020-03-06
  • suPAR news for acute kidney injury?
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Girish N. Nadkarni

    suPAR might serve as a biomarker for prediction of acute kidney injury with possible therapeutic implications.

    更新日期:2020-03-06
  • TAMing efferocytosis to fight tumors
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Christopher B. Rodell

    Preventing clearance of dying tumor cells elicits an inflammatory response by macrophages, supporting development of antitumor immunity in mice.

    更新日期:2020-03-06
  • “Eat breakfast like a king and dinner like a pauper”?
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Priyathama Vellanki

    Eating most of one’s calories at breakfast results in higher diet-induced thermogenesis.

    更新日期:2020-03-06
  • A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Michelle L. Cook Sangar, Emily J. Girard, Gene Hopping, Chunfeng Yin, Fiona Pakiam, Mi-Youn Brusniak, Elizabeth Nguyen, Raymond Ruff, Mesfin M. Gewe, Kelly Byrnes-Blake, Natalie W. Nairn, Dennis M. Miller, Christopher Mehlin, Andrew D. Strand, Andrew J. Mhyre, Colin E. Correnti, Roland K. Strong, Julian A. Simon, James M. Olson

    On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense peptides (CDPs) that rapidly accumulate in cartilage of the knees, ankles, hips, shoulders, and intervertebral discs after systemic administration. These

    更新日期:2020-03-06
  • Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Dongrui Wang, Renate Starr, Wen-Chung Chang, Brenda Aguilar, Darya Alizadeh, Sarah L. Wright, Xin Yang, Alfonso Brito, Aniee Sarkissian, Julie R. Ostberg, Li Li, Yanhong Shi, Margarita Gutova, Karen Aboody, Behnam Badie, Stephen J. Forman, Michael E. Barish, Christine E. Brown

    Although chimeric antigen receptor (CAR) T cells have demonstrated signs of antitumor activity against glioblastoma (GBM), tumor heterogeneity remains a critical challenge. To achieve broader and more effective GBM targeting, we developed a peptide-bearing CAR exploiting the GBM-binding potential of chlorotoxin (CLTX). We find that CLTX peptide binds a great proportion of tumors and constituent tumor

    更新日期:2020-03-06
  • A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Philip P. Vu, Alex K. Vaskov, Zachary T. Irwin, Phillip T. Henning, Daniel R. Lueders, Ann T. Laidlaw, Alicia J. Davis, Chrono S. Nu, Deanna H. Gates, R. Brent Gillespie, Stephen W. P. Kemp, Theodore A. Kung, Cynthia A. Chestek, Paul S. Cederna

    Peripheral nerves provide a promising source of motor control signals for neuroprosthetic devices. Unfortunately, the clinical utility of current peripheral nerve interfaces is limited by signal amplitude and stability. Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in

    更新日期:2020-03-06
  • Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Louise Leyre, Eugène Kroon, Claire Vandergeeten, Carlo Sacdalan, Donn J. Colby, Supranee Buranapraditkun, Alexandra Schuetz, Nitiya Chomchey, Mark de Souza, Wendy Bakeman, Rémi Fromentin, Suteeraporn Pinyakorn, Siriwat Akapirat, Rapee Trichavaroj, Suthat Chottanapund, Sopark Manasnayakorn, Rungsun Rerknimitr, Phandee Wattanaboonyoungcharoen, Jerome H. Kim, Sodsai Tovanabutra, Timothy W. Schacker, Robert

    The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion

    更新日期:2020-03-06
  • GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-03-04
    Samantha M. Fortin, Rachele K. Lipsky, Rinzin Lhamo, Jack Chen, Eun Kim, Tito Borner, Heath D. Schmidt, Matthew R. Hayes

    The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part through central GLP-1Rs in both the hypothalamus and the hindbrain. Here, we extend

    更新日期:2020-03-06
  • Echolocating electricity through the skull, in HD
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Raag Airan

    Ultrasound can make high-resolution images of electrical fields across intact human skulls.

    更新日期:2020-02-27
  • Cell therapies can bring insult to injury
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    James Ankrum

    Some cell therapies increase the risk of thromboembolism in trauma patients due to high tissue factor expression.

    更新日期:2020-02-27
  • Boosting arginine metabolism to regress atherosclerosis?
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Chiara Giannarelli

    The arginine metabolic pathway in macrophages is required to ensure continual efferocytosis and inflammation resolution.

    更新日期:2020-02-27
  • Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Madison R Mack,Jonathan R Brestoff,Melissa M Berrien-Elliott,Anna M Trier,Ting-Lin B Yang,Matthew McCullen,Patrick L Collins,Haixia Niu,Nancy D Bodet,Julia A Wagner,Eugene Park,Amy Z Xu,Fang Wang,Rebecca Chibnall,M Laurin Council,Carrie Heffington,Friederike Kreisel,David J Margolis,David Sheinbein,Paola Lovato,Eric Vivier,Marina Cella,Marco Colonna,Wayne M Yokoyama,Eugene M Oltz,Todd A Fehniger,Brian

    Atopic dermatitis (AD) is a widespread, chronic skin disease associated with aberrant allergic inflammation. Current treatments involve either broad or targeted immunosuppression strategies. However, enhancing the immune system to control disease remains untested. We demonstrate that patients with AD harbor a blood natural killer (NK) cell deficiency that both has diagnostic value and improves with

    更新日期:2020-02-27
  • Wnt-mediated endothelial transformation into mesenchymal stem cell-like cells induces chemoresistance in glioblastoma.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Menggui Huang,Duo Zhang,Janet Y Wu,Kun Xing,Eujin Yeo,Chunsheng Li,Lin Zhang,Eric Holland,Lutian Yao,Ling Qin,Zev A Binder,Donald M O'Rourke,Steven Brem,Constantinos Koumenis,Yanqing Gong,Yi Fan

    Therapeutic resistance remains a persistent challenge for patients with malignant tumors. Here, we reveal that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like cells in glioblastoma (GBM), driving tumor resistance to cytotoxic treatment. Transcriptome analysis by RNA sequencing (RNA-seq) revealed that ECs undergo mesenchymal transformation and stemness-like activation

    更新日期:2020-02-27
  • High-dose vitamin C enhances cancer immunotherapy.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Alessandro Magrì,Giovanni Germano,Annalisa Lorenzato,Simona Lamba,Rosaria Chilà,Monica Montone,Vito Amodio,Tommaso Ceruti,Francesco Sassi,Sabrina Arena,Sergio Abrignani,Maurizio D'Incalci,Massimo Zucchetti,Federica Di Nicolantonio,Alberto Bardelli

    Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic

    更新日期:2020-02-27
  • Tolerance induction and microglial engraftment after fetal therapy without conditioning in mice with Mucopolysaccharidosis type VII.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Quoc-Hung Nguyen,Russell G Witt,Bowen Wang,Carlo Eikani,Jeremy Shea,Lucas K Smith,Gabrielle Boyle,Jaclyn Cadaoas,Renan Sper,John D MacKenzie,Saul Villeda,Tippi C MacKenzie

    Mucopolysaccharidosis type VII (MPS7) is a lysosomal storage disorder (LSD) resulting from mutations in the β-glucuronidase gene, leading to multiorgan dysfunction and fetal demise. While postnatal enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation have resulted in some phenotypic improvements, prenatal treatment might take advantage of a unique developmental window to penetrate

    更新日期:2020-02-27
  • Natural killer cells get under your skin.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Graham Ogg

    Natural killer cells collaborate with type 2 immune cells to modulate atopic dermatitis pathogenesis (Mack et al, this issue).

    更新日期:2020-02-27
  • Liver macrophages inhibit the endogenous antioxidant response in obesity-associated insulin resistance.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-26
    Valerio Azzimato,Jennifer Jager,Ping Chen,Cecilia Morgantini,Laura Levi,Emelie Barreby,André Sulen,Carolina Oses,Joost Willerbrords,Connie Xu,Xidan Li,Joanne X Shen,Naveed Akbar,Lars Haag,Ewa Ellis,Kerstin Wålhen,Erik Näslund,Anders Thorell,Robin P Choudhury,Volker M Lauschke,Mikael Rydén,Siobhan M Craige,Myriam Aouadi

    Obesity and insulin resistance are risk factors for nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Because no approved medication nor an accurate and noninvasive diagnosis is currently available for NAFLD, there is a clear need to better understand the link between obesity and NAFLD. Lipid accumulation during obesity is known to be associated with oxidative

    更新日期:2020-02-27
  • Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-19
    Longbo Zhang,Tianxiang Huang,Shannon Teaw,Lena H Nguyen,Lawrence S Hsieh,Xuan Gong,Lindsay H Burns,Angélique Bordey

    Epilepsy treatments for patients with mechanistic target of rapamycin (mTOR) disorders, such as tuberous sclerosis complex (TSC) or focal cortical dysplasia type II (FCDII), are urgently needed. In these patients, the presence of focal cortical malformations is associated with the occurrence of lifelong epilepsy, leading to severe neurological comorbidities. Here, we show that the expression of the

    更新日期:2020-02-19
  • Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-19
    Stefan Haemmig,Dafeng Yang,Xinghui Sun,Debapria Das,Siavash Ghaffari,Roberto Molinaro,Lei Chen,Yihuan Deng,Dan Freeman,Norman Moullan,Yevgenia Tesmenitsky,A K M Khyrul Wara,Viorel Simion,Eugenia Shvartz,James F Lee,Tianlun Yang,Galina Sukova,Jarrod A Marto,Peter H Stone,Warren L Lee,Johan Auwerx,Peter Libby,Mark W Feinberg

    Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of Ldlr -/- mice on a high-cholesterol diet during lesion progression and regression phases. We found that the evolutionarily conserved lncRNA small nucleolar

    更新日期:2020-02-19
  • BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-02-19
    Florence Coussy,Rania El-Botty,Sophie Château-Joubert,Ahmed Dahmani,Elodie Montaudon,Sophie Leboucher,Ludivine Morisset,Pierre Painsec,Laura Sourd,Léa Huguet,Fariba Nemati,Jean-Luc Servely,Thibaut Larcher,Sophie Vacher,Adrien Briaux,Cécile Reyes,Philippe La Rosa,Georges Lucotte,Tatiana Popova,Pierre Foidart,Nor Eddine Sounni,Agnès Noel,Didier Decaudin,Laetitia Fuhrmann,Anne Salomon,Fabien Reyal,Christopher

    Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived

    更新日期:2020-02-19
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