显示样式:     当前期刊: Nature Medicine    加入关注    导出
我的关注
我的收藏
您暂时未登录!
登录
  • Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou

    Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions1,2. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics3. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy. Here, we report that MDSCs with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins. MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with strong upregulation of an antimicrobial gene network, and had potent antibacterial activity. MDSCs played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low weight, who are prone to NEC, had lower MDSC levels and suppressive activity than did infants with normal weight. Thus, the transitory presence of MDSCs may be critical for regulation of inflammation in newborns.

    更新日期:2018-01-15
  • Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall, Daniel Malouli, Roxanne M Gilbride, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Kurt T Randall, Andrea N Selseth, Parker Rundstrom, Lauren Herlache, Matthew S Lewis, Haesun Park, Shannon L Planer, John M Turner, Miranda Fischer, Christina Armstrong, Robert C Zweig, Joseph Valvo, Jackie M Braun, Smitha Shankar, Lenette Lu, Andrew W Sylwester, Alfred W Legasse, Martin Messerle, Michael A Jarvis, Lynn M Amon, Alan Aderem, Galit Alter, Dominick J Laddy, Michele Stone, Aurelio Bonavia, Thomas G Evans, Michael K Axthelm, Klaus Früh, Paul T Edlefsen, Louis J Picker

    Despite widespread use of the bacille Calmette–Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)—which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory T cell responses—can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both studies showed no TB disease by computed tomography scans or at necropsy after challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs were Mtb-culture-negative for all tissues, an exceptional long-term vaccine effect in the RM challenge model with the Erdman strain of Mtb. These results suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is possible if immune effector responses can intercept Mtb infection at its earliest stages.

    更新日期:2018-01-15
  • Positively selected enhancer elements endow osteosarcoma cells with metastatic competence
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri

    Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs). Met-VELs drive coordinated waves of gene expression during metastatic colonization of the lung. Met-VELs cluster nonrandomly in the genome, indicating that activity of these enhancers and expression of their associated gene targets are positively selected. As evidence of this causal association, osteosarcoma lung metastasis is inhibited by global interruptions of Met-VEL-associated gene expression via pharmacologic BET inhibition, by knockdown of AP-1 transcription factors that occupy Met-VELs, and by knockdown or functional inhibition of individual genes activated by Met-VELs, such as that encoding coagulation factor III/tissue factor (F3). We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. These findings indicate that Met-VELs and the genes they regulate play a functional role in metastasis and may be suitable targets for antimetastatic therapies.

    更新日期:2018-01-15
  • Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning

    The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2. Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated cancer cell growth and proliferation, increased cell death, and increased oxidative stress, which collectively contributed to antitumor responses in vitro and in vivo. This is the first study, to our knowledge, to demonstrate the utility of a pharmacological inhibitor of glutamine transport in oncology, representing a new class of targeted therapy and laying a framework for paradigm-shifting therapies targeting cancer cell metabolism.

    更新日期:2018-01-15
  • Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt– van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren

    Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL-107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in patient-derived xenografts, including melanoma, lung, pancreas and cervical cancer. By eliminating distinct populations in heterogeneous melanoma cell pools, AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth. Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise that rationalized combinatorial targeting of distinct populations in heterogeneous tumors may improve therapeutic effect, and merit clinical validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in mono- or combination therapy.

    更新日期:2018-01-15
  • A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment
    Nat. Med. (IF 29.886) Pub Date : 2018-01-15
    Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S Amidon, Neil F Bence

    The ubiquitin–proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment.

    更新日期:2018-01-15
  • Genomics in childhood acute myeloid leukemia comes of age
    Nat. Med. (IF 29.886) Pub Date : 2018-01-09
    Andrew M Brunner, Timothy A Graubert

    Genomics in childhood acute myeloid leukemia comes of ageGenomics in childhood acute myeloid leukemia comes of age, Published online: 09 January 2018; doi:10.1038/nm.4469A Children's Oncology Group study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

    更新日期:2018-01-10
  • Correction
    Nat. Med. (IF 29.886) Pub Date : 2018-01-09

    CorrectionCorrection, Published online: 09 January 2018; doi:10.1038/nm0118-5Correction

    更新日期:2018-01-10
  • Lipid metabolic reprogramming in hepatic ischemia–reperfusion injury
    Nat. Med. (IF 29.886) Pub Date : 2018-01-09
    Satdarshan P Monga

    Lipid metabolic reprogramming in hepatic ischemia–reperfusion injuryLipid metabolic reprogramming in hepatic ischemia–reperfusion injury, Published online: 09 January 2018; doi:10.1038/nm.4468In a recent study of hepatic ischemia–reperfusion injury (IRI), Zhang et al. use tandem 'omics' approaches in mice, pigs, and nonhuman primates to identify lipid metabolic reprogramming as a key determinant of IRI, thus providing novel mechanistic and therapeutic insights.

    更新日期:2018-01-10
  • Puzzling over privilege: How the immune system protects—and fails—the testes
    Nat. Med. (IF 29.886) Pub Date : 2018-01-09
    Shraddha Chakradhar

    Puzzling over privilege: How the immune system protects—and fails—the testesPuzzling over privilege: How the immune system protects—and fails—the testes, Published online: 09 January 2018; doi:10.1038/nm0118-2Puzzling over privilege: How the immune system protects—and fails—the testes

    更新日期:2018-01-10
  • The role of vaccines in preventing bacterial antimicrobial resistance
    Nat. Med. (IF 29.886) Pub Date : 2018-01-09
    Kathrin U Jansen, Charles Knirsch, Annaliesa S Anderson

    Antimicrobial resistance (AMR) and the associated morbidity and mortality due to bacterialpathogens have been increasing globally to alarming levels. The World Health Organization (WHO) hascalled for global action on AMR, supported worldwide by governments, health ministries and healthagencies. Many potential solutions to stem AMR are being discussed and implemented. These include increases in antimicrobial stewardship, investment in research and development to design new classes of antibiotics, and reduction of antibiotic use in rearing of livestock. However, vaccines as tools to reduce AMR have historically been under-recognized in these discussions, even though their effectiveness in reducing disease and AMR is well documented. This review article seeks to highlight the value of vaccines as an additional modality to combat AMR globally, using select examples. It also will provide perspectives on how vaccines could be more effectively used in this effort.

    更新日期:2018-01-10
  • Thinking big in mental health
    Nat. Med. (IF 29.886) Pub Date : 

    Thinking big in mental health Thinking big in mental health, Published online: 09 January 2018; doi:10.1038/nm.4471 Mental illnesses impose a grave disease burden worldwide, yet progress in managing and treating them has largely stalled. Harnessing the power of big data may break the current impasse and open new avenues for better diagnosis, treatment and prevention of these devastating illnesses.

    更新日期:2018-01-10
  • Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms
    Nat. Med. (IF 29.886) Pub Date : 2018-01-08
    Marco Bezzi, Nina Seitzer, Tomoki Ishikawa, Markus Reschke, Ming Chen, Guocan Wang, Caitlin Mitchell, Christopher Ng, Jesse Katon, Andrea Lunardi, Sabina Signoretti, John G Clohessy, Jiangwen Zhang, Pier Paolo Pandolfi

    Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes—results with important therapeutic implications. Further, we showed these qualitative differences in transcriptomic analysis of human prostate cancer samples. These data suggest that patient stratification on the basis of integrated genotypic–immunophenotypic analyses may be necessary for successful clinical trials and tailored precision immunological therapies.

    更新日期:2018-01-08
  • Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury
    Nat. Med. (IF 29.886) Pub Date : 2018-01-08
    Koshu Okubo, Miho Kurosawa, Mako Kamiya, Yasuteru Urano, Akari Suzuki, Kazuhiko Yamamoto, Koji Hase, Koichiro Homma, Junichi Sasaki, Hiroaki Miyauchi, Tatsuo Hoshino, Matsuhiko Hayashi, Tanya N Mayadas, Junichi Hirahashi

    Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation1. The muscle damage most often results from strenuous exercise, muscle hypoxia, medications, or drug abuse and can lead to life-threatening complications, such as acute kidney injury (AKI)1. Rhabdomyolysis and the AKI complication can also occur during crush syndrome, an emergency condition that commonly occurs in victims of natural disasters, such as earthquakes, and man-made disasters, such as wars and terrorism2. Myoglobin released from damaged muscle is believed to trigger renal dysfunction in this form of AKI. Recently, macrophages were implicated in the disease pathogenesis of rhabdomyolysis-induced AKI3,4, but the precise molecular mechanism remains unclear. In the present study, we show that macrophages released extracellular traps (ETs) comprising DNA fibers and granule proteins in a mouse model of rhabdomyolysis. Heme-activated platelets released from necrotic muscle cells during rhabdomyolysis enhanced the production of macrophage extracellular traps (METs) through increasing intracellular reactive oxygen species generation and histone citrullination. Here we report, for the first time to our knowledge, this unanticipated role for METs and platelets as a sensor of myoglobin-derived heme in rhabdomyolysis-induced AKI. This previously unknown mechanism might be targeted for treatment of the disease. Finally, we found a new therapeutic tool for prevention of AKI after rhabdomyolysis, which might rescue some sufferers of this pathology.

    更新日期:2018-01-08
  • High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
    Nat. Med. (IF 29.886) Pub Date : 2018-01-08
    Carsten Krieg, Malgorzata Nowicka, Silvia Guglietta, Sabrina Schindler, Felix J Hartmann, Lukas M Weber, Reinhard Dummer, Mark D Robinson, Mitchell P Levesque, Burkhard Becher

    Immune-checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable responses. Therefore, predictive biomarkers of a clinical response are urgently needed. Here we used high-dimensional single-cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of anti-PD-1 immunotherapy. During therapy, we observed a clear response to immunotherapy in the T cell compartment. However, before commencing therapy, a strong predictor of progression-free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16−HLA-DRhi monocytes. We confirmed this by conventional flow cytometry in an independent, blinded validation cohort, and we propose that the frequency of monocytes in PBMCs may serve in clinical decision support.

    更新日期:2018-01-08
  • Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury
    Nat. Med. (IF 29.886) Pub Date : 2018-01-08
    Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos, Shieh Jae-Hung, Lauren F Young, Amina Lazrak, Odette M Smith, Sophie Lieberman, Fabiana Kreines, Yusuke Shono, Tobias Wertheimer, Robert R Jenq, Alan M Hanash, Prema Narayan, Zhenmin Lei, Malcolm A Moore, Hans-Peter Kiem, Marcel R M van den Brink, Jarrod A Dudakov

    There is a substantial unmet clinical need for new strategies to protect the hematopoietic stem cell (HSC) pool and regenerate hematopoiesis after radiation injury from either cancer therapy or accidental exposure1,2. Increasing evidence suggests that sex hormones, beyond their role in promoting sexual dimorphism, regulate HSC self-renewal, differentiation, and proliferation3,4,5. We and others have previously reported that sex-steroid ablation promotes bone marrow (BM) lymphopoiesis and HSC recovery in aged and immunodepleted mice5,6,7. Here we found that a luteinizing hormone (LH)-releasing hormone antagonist (LHRH-Ant), currently in wide clinical use for sex-steroid inhibition, promoted hematopoietic recovery and mouse survival when administered 24 h after an otherwise-lethal dose of total-body irradiation (L-TBI). Unexpectedly, this protective effect was independent of sex steroids and instead relied on suppression of LH levels. Human and mouse long-term self-renewing HSCs (LT-HSCs) expressed high levels of the LH/choriogonadotropin receptor (LHCGR) and expanded ex vitro when stimulated with LH. In contrast, the suppression of LH after L-TBI inhibited entry of HSCs into the cell cycle, thus promoting HSC quiescence and protecting the cells from exhaustion. These findings reveal a role of LH in regulating HSC function and offer a new therapeutic approach for hematopoietic regeneration after hematopoietic injury.

    更新日期:2018-01-08
  • The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis
    Nat. Med. (IF 29.886) Pub Date : 2018-01-01
    Yan-Xiao Ji, Zan Huang, Xia Yang, Xiaozhan Wang, Ling-Ping Zhao, Pi-Xiao Wang, Xiao-Jing Zhang, Michele Alves-Bezerra, Lin Cai, Peng Zhang, Yue-Xin Lu, Lan Bai, Mao-Mao Gao, Huan Zhao, Song Tian, Yong Wang, Zhi-Xiang Huang, Xue-Yong Zhu, Yan Zhang, Jun Gong, Zhi-Gang She, Feng Li, David E Cohen, Hongliang Li

    Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. Lack of effective pharmacotherapies for NASH is largely attributable to an incomplete understanding of its pathogenesis. The deubiquitinase cylindromatosis (CYLD) plays key roles in inflammation and cancer. Here we identified CYLD as a suppressor of NASH in mice and in monkeys. CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity. We observed that overexpression of Cyld in hepatocytes concomitantly inhibits lipid accumulation, insulin resistance, inflammation and fibrosis in mice with NASH induced in an experimental setting. Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK–p38 cascades. Notably, reconstitution of hepatic CYLD expression effectively reverses disease progression in mice with dietary or genetically induced NASH and in high-fat diet–fed monkeys predisposed to metabolic syndrome. Collectively, our findings demonstrate that CYLD mitigates NASH severity and identify the CYLD–TAK1 axis as a promising therapeutic target for management of the disease.

    更新日期:2018-01-01
  • Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma
    Nat. Med. (IF 29.886) Pub Date : 2018-01-01
    Haijun Wen, Huajuan Ma, Qichun Cai, Suxia Lin, Xinxing Lei, Bin He, Sijin Wu, Zifeng Wang, Yan Gao, Wensheng Liu, Weiping Liu, Qian Tao, Zijie Long, Min Yan, Dali Li, Keith W. Kelley, Yongliang Yang, Huiqiang Huang, Quentin Liu

    Hemophagocytic syndrome (HPS) is a fatal hyperinflammatory disease with a poorly understood mechanism that occurs most frequently in extranodal natural killer/T cell lymphoma (ENKTL). Through exome sequencing of ENKTL tumor–normal samples, we have identified a hotspot mutation (c.419T>C) in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene, encoding a V140A variant of ECSIT. ECSIT-V140A activated NF-κB more potently than the wild-type protein owing to its increased affinity for the S100A8 and S100A9 heterodimer, which promotes NADPH oxidase activity. ECSIT-T419C knock-in mice showed higher peritoneal NADPH oxidase activity than mice with wild-type ECSIT in response to LPS. ECSIT-T419C-transfected ENKTL cell lines produced tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which induced macrophage activation and massive cytokine secretion in cell culture and mouse xenografts. In individuals with ENKTL, ECSIT-V140A was associated with activation of NF-κB, higher HPS incidence, and poor prognosis. The immunosuppressive drug thalidomide prevented NF-κB from binding to the promoters of its target genes (including TNF and IFNG), and combination treatment with thalidomide and dexamethasone extended survival of mice engrafted with ECSIT-T419C-transfected ENKTL cells. We added thalidomide to the conventional dexamethasone-containing therapy regimen for two patients with HPS who expressed ECSIT-V140A, and we observed reversal of their HPS and disease-free survival for longer than 3 years. These findings provide mechanistic insights and a potential therapeutic strategy for ENKTL-associated HPS.

    更新日期:2018-01-01
  • An ALOX12–12-HETE–GPR31 signaling axis is a key mediator of hepatic ischemia–reperfusion injury
    Nat. Med. (IF 29.886) Pub Date : 2017-12-11
    Xiao-Jing Zhang, Xu Cheng, Zhen-Zhen Yan, Jing Fang, Xiaozhan Wang, Weijun Wang, Zhen-Yu Liu, Li-Jun Shen, Peng Zhang, Pi-Xiao Wang, Rufang Liao, Yan-Xiao Ji, Jun-Yong Wang, Song Tian, Xue-Yong Zhu, Yan Zhang, Rui-Feng Tian, Lin Wang, Xin-Liang Ma, Zan Huang, Zhi-Gang She, Hongliang Li

    An ALOX12–12-HETE–GPR31 signaling axis is a key mediator of hepatic ischemia–reperfusion injury An ALOX12–12-HETE–GPR31 signaling axis is a key mediator of hepatic ischemia–reperfusion injury, Published online: 11 December 2017; doi:10.1038/nm.4451 ALOX12-mediated generation of 12-HETE leads to GPR31 activation and liver injury in ischemia–reperfusion, which can be targeted in a nonhuman primate model to improve outcome.

    更新日期:2017-12-11
  • The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis
    Nat. Med. (IF 29.886) Pub Date : 2017-12-11
    Peng Zhang, Pi-Xiao Wang, Ling-Ping Zhao, Xin Zhang, Yan-Xiao Ji, Xiao-Jing Zhang, Chun Fang, Yue-Xin Lu, Xia Yang, Mao-Mao Gao, Yan Zhang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin-Liang Ma, Feng Li, Zhihua Wang, Zan Huang, Zhi-Gang She, Hongliang Li

    The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis, Published online: 11 December 2017; doi:10.1038/nm.4453 The deubiquitinase TNFAIP3 suppresses the kinase ASK1 to ameliorate nonalcoholic fatty liver disease.

    更新日期:2017-12-11
  • A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway
    Nat. Med. (IF 29.886) Pub Date : 2017-12-11
    Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs

    A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway, Published online: 11 December 2017; doi:10.1038/nm.4452 A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

    更新日期:2017-12-11
  • The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions
    Nat. Med. (IF 29.886) Pub Date : 2017-12-11
    Hamid Bolouri, Jason E Farrar, Timothy Triche Jr, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi

    The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions, Published online: 11 December 2017; doi:10.1038/nm.4439 A comprehensive molecular analysis of almost 1,000 pediatric subjects with acute myeloid leukemia (AML) uncovers widespread differences in pediatric AML as compared to adult AML, including a higher frequency of structural variants and different mutational patterns and epigenetic signatures. Future studies are needed to characterize the functional relevance of these alterations and to explore age-tailored therapies to improve disease control in younger patients.

    更新日期:2017-12-11
  • The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Ross A Cardarelli, Karen Jones, Lucie I Pisella, Heike J Wobst, Lisa J McWilliams, Paul M Sharpe, Matthew P Burnham, David J Baker, Ilona Chudotvorova, Justine Guyot, Liliya Silayeva, Danielle H Morrow, Niek Dekker, Stephen Zicha, Paul A Davies, Jörg Holenz, Mark E Duggan, John Dunlop, Robert J Mather, Qi Wang, Igor Medina, Nicholas J Brandon, Tarek Z Deeb, Stephen J Moss

    The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity The small molecule CLP257 does not modify activity of the K+–Cl co-transporter KCC2 but does potentiate GABAA receptor activity, Published online: 07 December 2017; doi:10.1038/nm.4442 The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity

    更新日期:2017-12-07
  • Organoids lead the cancer attack
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Amber R Smith, Calvin J Kuo

    Organoids lead the cancer attack Organoids lead the cancer attack, Published online: 07 December 2017; doi:10.1038/nm.4454 In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.

    更新日期:2017-12-07
  • Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst, Alicia Franklin, Daniela M Santos, Paula Grasberger, Neil Ahluwalia, Sydney B Montesi, Barry S Shea, Katharine E Black, Rachel Knipe, Meryem Blati, Murray Baron, Brian Wu, Hassan Fahmi, Rajiv Gandhi, Annie Pardo, Moisés Selman, Jiangping Wu, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Andrew M Tager, Mohit Kapoor

    Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis, Published online: 07 December 2017; doi:10.1038/nm1217-1499b Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis

    更新日期:2017-12-07
  • Notable advances 2017
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Tanya Bondar, Javier Carmona, Kate Gao, Brett Benedetti, Michael Basson, Randy Levinson, Hannah Stower, Alison Farrell

    Notable advances 2017 Notable advances 2017, Published online: 07 December 2017; doi:10.1038/nm1217-1387 This past year included numerous research studies that broke the mold and elucidated new biology and drug targets. Here are some of the exciting papers from 2017 that moved biomedicine forward.

    更新日期:2017-12-07
  • Correction
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07

    Correction Correction, Published online: 07 December 2017; doi:10.1038/nm1217-1391 Correction

    更新日期:2017-12-07
  • Targeted cellular immunotherapy for T cell malignancies
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Teresa Palomero, Adolfo Ferrando

    Targeted cellular immunotherapy for T cell malignancies Targeted cellular immunotherapy for T cell malignancies, Published online: 07 December 2017; doi:10.1038/nm.4458 In a recent study, Maciocia et al. develop a novel T cell receptor beta (TCRB) constant C1-chain-directed cellular immunotherapy for the treatment of T cell malignancies.

    更新日期:2017-12-07
  • Reply to The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Martin Gagnon, Marc J Bergeron, Jimena Perez-Sanchez, Isabel Plasencia-Fernández, Louis-Etienne Lorenzo, Antoine G Godin, Annie Castonguay, Robert P Bonin, Yves De Koninck

    Reply to The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity Reply to The small molecule CLP257 does not modify activity of the K+–Cl co-transporter KCC2 but does potentiate GABAA receptor activity, Published online: 07 December 2017; doi:10.1038/nm.4449 Reply to The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity

    更新日期:2017-12-07
  • Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure
    Nat. Med. (IF 29.886) Pub Date : 2017-12-07
    Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov, Magdalena Kriel, Tran Van, Ray Y Chen, James Warwick, Laura E Via, Taeksun Song, Myungsun Lee, Gary Schoolnik, Gerard Tromp, David Alland, Clifton E Barry III, Jill Winter, Gerhard Walzl, the Catalysis TB–Biomarker Consortium

    Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure, Published online: 07 December 2017; doi:10.1038/nm1217-1499a Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure

    更新日期:2017-12-07
  • Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
    Nat. Med. (IF 29.886) Pub Date : 2017-12-04
    Guoying Yu, Argyris Tzouvelekis, Rong Wang, Jose D Herazo-Maya, Gabriel H Ibarra, Anup Srivastava, Joao Pedro Werneck de Castro, Giuseppe DeIuliis, Farida Ahangari, Tony Woolard, Nachelle Aurelien, Rafael Arrojo e Drigo, Ye Gan, Morven Graham, Xinran Liu, Robert J Homer, Thomas S Scanlan, Praveen Mannam, Patty J Lee, Erica L Herzog, Antonio C Bianco, Naftali Kaminski

    Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function, Published online: 04 December 2017; doi:10.1038/nm.4447 Thyroid hormone improves mitochondrial function and dynamics in lung epithelium to reduce pulmonary fibrosis in mice.

    更新日期:2017-12-05
  • Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation
    Nat. Med. (IF 29.886) Pub Date : 2017-12-04
    Zhuohao He, Jing L Guo, Jennifer D McBride, Sneha Narasimhan, Hyesung Kim, Lakshmi Changolkar, Bin Zhang, Ronald J Gathagan, Cuiyong Yue, Christopher Dengler, Anna Stieber, Magdalena Nitla, Douglas A Coulter, Ted Abel, Kurt R Brunden, John Q Trojanowski, Virginia M-Y Lee

    Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation, Published online: 04 December 2017; doi:10.1038/nm.4443 Through injection of human Alzheimer's disease (AD) brain extracts containing pathological tau protein into transgenic mouse lines harboring different levels of amyloid plaque burden, the authors find that the presence of amyloid plaques modifies endogenous pools of tau protein, creating a unique environment required for the seeding and spreading of distinct tau pathologies.

    更新日期:2017-12-05
  • cGAS drives noncanonical-inflammasome activation in age-related macular degeneration
    Nat. Med. (IF 29.886) Pub Date : 2017-11-27
    Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati

    cGAS drives noncanonical-inflammasome activation in age-related macular degeneration cGAS drives noncanonical-inflammasome activation in age-related macular degeneration, Published online: 27 November 2017; doi:10.1038/nm.4450 Degeneration of the retinal pigment epithelium is a hallmark of geographic atrophy, a type of age-related macular degeneration. Kerur et al. show that this degeneration results from a multistep pathway in which mitochondrial dysfunction in RPE cells, triggered by accumulation of Alu RNA, leads to activation of the noncanonical inflammasome via a cGAS–STING–IRF3 signaling axis.

    更新日期:2017-11-28
  • cGAS drives noncanonical-inflammasome activation in age-related macular degeneration
    Nat. Med. (IF 29.886) Pub Date : 2017-11-27
    Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati

    cGAS drives noncanonical-inflammasome activation in age-related macular degeneration cGAS drives noncanonical-inflammasome activation in age-related macular degeneration, Published online: 27 November 2017; doi:10.1038/nm.4450 Degeneration of the retinal pigment epithelium is a hallmark of geographic atrophy, a type of age-related macular degeneration. Kerur et al. show that this degeneration results from a multistep pathway in which mitochondrial dysfunction in RPE cells, triggered by accumulation of Alu RNA, leads to activation of the noncanonical inflammasome via a cGAS–STING–IRF3 signaling axis.

    更新日期:2017-11-28
  • Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow
    Nat. Med. (IF 29.886) Pub Date : 2017-11-20
    Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello, Daniel Lucas

    Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow, Published online: 20 November 2017; doi:10.1038/nm.4448 In the bone marrow, granulocyte-derived TNFα acts on endothelial cells to maintain the vasculature under steady-state conditions and to promote its regeneration after injury or transplantation.

    更新日期:2017-11-21
  • CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy
    Nat. Med. (IF 29.886) Pub Date : 2017-11-20
    Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall

    CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy, Published online: 20 November 2017; doi:10.1038/nm.4441 Fry et al. report the first results from a human trial of a CD22-directed chimeric antigen receptor (CAR) T cell therapy providing evidence of efficacy in the treatment of pre–B cell acute lymphoblastic leukemia that is immunotherapy-naive or resistant to CD19-directed CAR T cells.

    更新日期:2017-11-21
  • Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow
    Nat. Med. (IF 29.886) Pub Date : 2017-11-20
    Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello, Daniel Lucas

    Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow, Published online: 20 November 2017; doi:10.1038/nm.4448 In the bone marrow, granulocyte-derived TNFα acts on endothelial cells to maintain the vasculature under steady-state conditions and to promote its regeneration after injury or transplantation.

    更新日期:2017-11-21
  • CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy
    Nat. Med. (IF 29.886) Pub Date : 2017-11-20
    Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall

    CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy, Published online: 20 November 2017; doi:10.1038/nm.4441 Fry et al. report the first results from a human trial of a CD22-directed chimeric antigen receptor (CAR) T cell therapy providing evidence of efficacy in the treatment of pre–B cell acute lymphoblastic leukemia that is immunotherapy-naive or resistant to CD19-directed CAR T cells.

    更新日期:2017-11-21
  • Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
    Nat. Med. (IF 29.886) Pub Date : 2017-11-13
    Laura Broutier, Gianmarco Mastrogiovanni, Monique MA Verstegen, Hayley E Francies, Lena Morrill Gavarró, Charles R Bradshaw, George E Allen, Robert Arnes-Benito, Olga Sidorova, Marcia P Gaspersz, Nikitas Georgakopoulos, Bon-Kyoung Koo, Sabine Dietmann, Susan E Davies, Raaj K Praseedom, Ruby Lieshout, Jan N M IJzermans, Stephen J Wigmore, Kourosh Saeb-Parsy, Mathew J Garnett, Luc JW van der Laan, Meritxell Huch

    Human primary liver cancer–derived organoid cultures for disease modeling and drug screening Human primary liver cancer–derived organoid cultures for disease modeling and drug screening, Published online: 13 November 2017; doi:10.1038/nm.4438 NatureArticleSnippet(type=short-summary, markup= Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment. , isJats=true)

    更新日期:2017-11-13
  • Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies
    Nat. Med. (IF 29.886) Pub Date : 2017-11-13
    Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca, Shimobi C Onuoha, Mateusz Legut, David K Cole, Andrew K Sewell, Giuseppe Gritti, Joan Somja, Miguel A Piris, Karl S Peggs, David C Linch, Teresa Marafioti, Martin A Pule

    Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies, Published online: 13 November 2017; doi:10.1038/nm.4444 NatureArticleSnippet(type=short-summary, markup= Pule and colleagues identify the TCR β-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1+ T cells while sparing nearly one-third of normal TCRB2+ T cells. , isJats=true)

    更新日期:2017-11-13
  • UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis
    Nat. Med. (IF 29.886) Pub Date : 2017-11-13
    Kenji Ikeda, Qianqian Kang, Takeshi Yoneshiro, Joao Paulo Camporez, Hiroko Maki, Mayu Homma, Kosaku Shinoda, Yong Chen, Xiaodan Lu, Pema Maretich, Kazuki Tajima, Kolapo M Ajuwon, Tomoyoshi Soga, Shingo Kajimura

    UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis, Published online: 13 November 2017; doi:10.1038/nm.4429 NatureArticleSnippet(type=short-summary, markup= Calcium cycling induced by the SERCA2b–RyR2 pathway in beige fat cells allows for thermogenic activity independent of UCP1. , isJats=true)

    更新日期:2017-11-13
  • Enhancing the precision of genetic lineage tracing using dual recombinases
    Nat. Med. (IF 29.886) Pub Date : 2017-11-13
    Lingjuan He, Yan Li, Yi Li, Wenjuan Pu, Xiuzhen Huang, Xueying Tian, Yue Wang, Hui Zhang, Qiaozhen Liu, Libo Zhang, Huan Zhao, Juan Tang, Hongbin Ji, Dongqing Cai, Zhibo Han, Zhongchao Han, Yu Nie, Shengshou Hu, Qing-Dong Wang, Ruilin Sun, Jian Fei, Fengchao Wang, Ting Chen, Yan Yan, Hefeng Huang, William T Pu, Bin Zhou

    Enhancing the precision of genetic lineage tracing using dual recombinases Enhancing the precision of genetic lineage tracing using dual recombinases, Published online: 13 November 2017; doi:10.1038/nm.4437 NatureArticleSnippet(type=short-summary, markup= Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver. , isJats=true)

    更新日期:2017-11-13
  • Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
    Nat. Med. (IF 29.886) Pub Date : 
    Laura Broutier, Gianmarco Mastrogiovanni, Monique MA Verstegen, Hayley E Francies, Lena Morrill Gavarró, Charles R Bradshaw, George E Allen, Robert Arnes-Benito, Olga Sidorova, Marcia P Gaspersz, Nikitas Georgakopoulos, Bon-Kyoung Koo, Sabine Dietmann, Susan E Davies, Raaj K Praseedom, Ruby Lieshout, Jan N M IJzermans, Stephen J Wigmore, Kourosh Saeb-Parsy, Mathew J Garnett, Luc JW van der Laan, Meritxell Huch

    Human primary liver cancer–derived organoid cultures for disease modeling and drug screening Human primary liver cancer–derived organoid cultures for disease modeling and drug screening, Published online: 13 November 2017; doi:10.1038/nm.4438 NatureArticleSnippet(type=short-summary, markup= Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment. , isJats=true)

    更新日期:2017-11-13
  • Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies
    Nat. Med. (IF 29.886) Pub Date : 
    Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca, Shimobi C Onuoha, Mateusz Legut, David K Cole, Andrew K Sewell, Giuseppe Gritti, Joan Somja, Miguel A Piris, Karl S Peggs, David C Linch, Teresa Marafioti, Martin A Pule

    Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies, Published online: 13 November 2017; doi:10.1038/nm.4444 NatureArticleSnippet(type=short-summary, markup= Pule and colleagues identify the TCR β-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1+ T cells while sparing nearly one-third of normal TCRB2+ T cells. , isJats=true)

    更新日期:2017-11-13
  • UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis
    Nat. Med. (IF 29.886) Pub Date : 
    Kenji Ikeda, Qianqian Kang, Takeshi Yoneshiro, Joao Paulo Camporez, Hiroko Maki, Mayu Homma, Kosaku Shinoda, Yong Chen, Xiaodan Lu, Pema Maretich, Kazuki Tajima, Kolapo M Ajuwon, Tomoyoshi Soga, Shingo Kajimura

    UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis, Published online: 13 November 2017; doi:10.1038/nm.4429 NatureArticleSnippet(type=short-summary, markup= Calcium cycling induced by the SERCA2b–RyR2 pathway in beige fat cells allows for thermogenic activity independent of UCP1. , isJats=true)

    更新日期:2017-11-13
  • Enhancing the precision of genetic lineage tracing using dual recombinases
    Nat. Med. (IF 29.886) Pub Date : 
    Lingjuan He, Yan Li, Yi Li, Wenjuan Pu, Xiuzhen Huang, Xueying Tian, Yue Wang, Hui Zhang, Qiaozhen Liu, Libo Zhang, Huan Zhao, Juan Tang, Hongbin Ji, Dongqing Cai, Zhibo Han, Zhongchao Han, Yu Nie, Shengshou Hu, Qing-Dong Wang, Ruilin Sun, Jian Fei, Fengchao Wang, Ting Chen, Yan Yan, Hefeng Huang, William T Pu, Bin Zhou

    Enhancing the precision of genetic lineage tracing using dual recombinases Enhancing the precision of genetic lineage tracing using dual recombinases, Published online: 13 November 2017; doi:10.1038/nm.4437 NatureArticleSnippet(type=short-summary, markup= Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver. , isJats=true)

    更新日期:2017-11-13
  • Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedán, Theodora-Dorita Tsourouktsoglou, Yee Man Ching, Coraline Radermecker, Heidi Makrinioti, Julia Aniscenko, Michael R Edwards, Roberto Solari, Frédéric Farnir, Venizelos Papayannopoulos, Fabrice Bureau, Thomas Marichal, Sebastian L Johnston

    Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation, Published online: 07 November 2017; doi:10.1038/nm1117-1384a

    更新日期:2017-11-08
  • Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Joshua N Farr, Ming Xu, Megan M Weivoda, David G Monroe, Daniel G Fraser, Jennifer L Onken, Brittany A Negley, Jad G Sfeir, Mikolaj B Ogrodnik, Christine M Hachfeld, Nathan K LeBrasseur, Matthew T Drake, Robert J Pignolo, Tamar Pirtskhalava, Tamara Tchkonia, Merry Jo Oursler, James L Kirkland, Sundeep Khosla

    Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice, Published online: 07 November 2017; doi:10.1038/nm1117-1384c

    更新日期:2017-11-08
  • Barrier-tissue macrophages: functional adaptation to environmental challenges
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Allan McI Mowat, Charlotte L Scott, Calum C Bain

    Barrier-tissue macrophages: functional adaptation to environmental challenges Barrier-tissue macrophages: functional adaptation to environmental challenges, Published online: 07 November 2017; doi:10.1038/nm.4430 NatureArticleSnippet(type=short-summary, markup= Mowat, Scott and Bain discuss the functions of barrier-tissue macrophages in homeostasis and disease, and how these are shaped by their local environment. , isJats=true)

    更新日期:2017-11-08
  • Can NK cells purge HIV sanctuaries?
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Madeleine J Bunders, Marcus Altfeld

    Can NK cells purge HIV sanctuaries? Can NK cells purge HIV sanctuaries?, Published online: 07 November 2017; doi:10.1038/nm.4434 NatureArticleSnippet(type=standfirst, markup= A recent study identifies a population of CXCR5+ natural killer (NK) cells patrolling B cell follicles in simian immunodeficiency virus (SIV)-infected African green monkeys that might contribute to the lack of disease progression in this nonpathogenic model. , isJats=true)

    更新日期:2017-11-08
  • Long-range hypoxia signaling in NAFLD
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Edward L LaGory, Amato J Giaccia

    Long-range hypoxia signaling in NAFLD Long-range hypoxia signaling in NAFLD, Published online: 07 November 2017; doi:10.1038/nm.4436 NatureArticleSnippet(type=standfirst, markup= A recent study describes a role for hypoxic signaling in the small intestine in the etiology of nonalcoholic fatty liver disease (NAFLD) and suggests that HIF-2α inhibitors may be an effective option for the treatment of this disease. , isJats=true)

    更新日期:2017-11-08
  • Macrophages dispose of catecholamines in adipose tissue
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Michael P Czech

    Macrophages dispose of catecholamines in adipose tissue Macrophages dispose of catecholamines in adipose tissue, Published online: 07 November 2017; doi:10.1038/nm.4440 NatureArticleSnippet(type=standfirst, markup= Recent research has identified sympathetic neuron–associated macrophages in adipose tissue that take up and degrade catecholamines released from neurons. Obesity and aging enhance this system, decreasing responses to cold stress and starvation. , isJats=true)

    更新日期:2017-11-08
  • Predictable response: Finding optimal drugs and doses using artificial intelligence
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Shraddha Chakradhar

    Predictable response: Finding optimal drugs and doses using artificial intelligence Predictable response: Finding optimal drugs and doses using artificial intelligence, Published online: 07 November 2017; doi:10.1038/nm1117-1244

    更新日期:2017-11-08
  • Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Carrie Arnold

    Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach, Published online: 07 November 2017; doi:10.1038/nm1117-1248

    更新日期:2017-11-08
  • Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedán, Theodora-Dorita Tsourouktsoglou, Yee Man Ching, Coraline Radermecker, Heidi Makrinioti, Julia Aniscenko, Michael R Edwards, Roberto Solari, Frédéric Farnir, Venizelos Papayannopoulos, Fabrice Bureau, Thomas Marichal, Sebastian L Johnston

    Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation, Published online: 07 November 2017; doi:10.1038/nm1117-1384a

    更新日期:2017-11-08
  • Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Joshua N Farr, Ming Xu, Megan M Weivoda, David G Monroe, Daniel G Fraser, Jennifer L Onken, Brittany A Negley, Jad G Sfeir, Mikolaj B Ogrodnik, Christine M Hachfeld, Nathan K LeBrasseur, Matthew T Drake, Robert J Pignolo, Tamar Pirtskhalava, Tamara Tchkonia, Merry Jo Oursler, James L Kirkland, Sundeep Khosla

    Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice Corrigendum: Targeting cellular senescence prevents age-related bone loss in mice, Published online: 07 November 2017; doi:10.1038/nm1117-1384c

    更新日期:2017-11-08
  • Barrier-tissue macrophages: functional adaptation to environmental challenges
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Allan McI Mowat, Charlotte L Scott, Calum C Bain

    Barrier-tissue macrophages: functional adaptation to environmental challenges Barrier-tissue macrophages: functional adaptation to environmental challenges, Published online: 07 November 2017; doi:10.1038/nm.4430 NatureArticleSnippet(type=short-summary, markup= Mowat, Scott and Bain discuss the functions of barrier-tissue macrophages in homeostasis and disease, and how these are shaped by their local environment. , isJats=true)

    更新日期:2017-11-08
  • Can NK cells purge HIV sanctuaries?
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Madeleine J Bunders, Marcus Altfeld

    Can NK cells purge HIV sanctuaries? Can NK cells purge HIV sanctuaries?, Published online: 07 November 2017; doi:10.1038/nm.4434 NatureArticleSnippet(type=standfirst, markup= A recent study identifies a population of CXCR5+ natural killer (NK) cells patrolling B cell follicles in simian immunodeficiency virus (SIV)-infected African green monkeys that might contribute to the lack of disease progression in this nonpathogenic model. , isJats=true)

    更新日期:2017-11-08
  • Long-range hypoxia signaling in NAFLD
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Edward L LaGory, Amato J Giaccia

    Long-range hypoxia signaling in NAFLD Long-range hypoxia signaling in NAFLD, Published online: 07 November 2017; doi:10.1038/nm.4436 NatureArticleSnippet(type=standfirst, markup= A recent study describes a role for hypoxic signaling in the small intestine in the etiology of nonalcoholic fatty liver disease (NAFLD) and suggests that HIF-2α inhibitors may be an effective option for the treatment of this disease. , isJats=true)

    更新日期:2017-11-08
  • Macrophages dispose of catecholamines in adipose tissue
    Nat. Med. (IF 29.886) Pub Date : 2017-11-07
    Michael P Czech

    Macrophages dispose of catecholamines in adipose tissue Macrophages dispose of catecholamines in adipose tissue, Published online: 07 November 2017; doi:10.1038/nm.4440 NatureArticleSnippet(type=standfirst, markup= Recent research has identified sympathetic neuron–associated macrophages in adipose tissue that take up and degrade catecholamines released from neurons. Obesity and aging enhance this system, decreasing responses to cold stress and starvation. , isJats=true)

    更新日期:2017-11-08
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
化学 • 材料 期刊列表