Science translational medicine (Sci Transl Med)

Publisher: American Association for the Advancement of Science

Journal description

Current impact factor: 14.41

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 14.414
2012 Impact Factor 10.757
2011 Impact Factor 7.804
2010 Impact Factor 3.511

Impact factor over time

Impact factor

Additional details

5-year impact 10.48
Cited half-life 1.80
Immediacy index 3.69
Eigenfactor 0.04
Article influence 5.18
ISSN 1946-6242

Publisher details

American Association for the Advancement of Science

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Pre-print may be considered prior publication
    • Pre-print on not-for-profit preprint servers where allowed, please contact editors for clarification
    • Cannot archive until publication
    • Authors retain copyright
    • On author's personal website or institutional repository
    • Publisher's version/PDF cannot be used
    • Must link to publisher version
    • Set statement must accompany post-print (see policy)
    • Published source must be acknowledged with DOI
    • Authors covered by funding agency rules, may post author's post-print in PubMed Central or funder's designated repository after a 6 month embargo
    • Authors covered by funding agency rules, must state on submission, for article to be released in PubMed Central or funder's designated repository after 6 months after publication.
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Innate natural killer (NK) cells are diverse at the single-cell level because of variegated expressions of activating and inhibitory receptors, yet the developmental roots and functional consequences of this diversity remain unknown. Because NK cells are critical for antiviral and antitumor responses, a better understanding of their diversity could lead to an improved ability to harness them therapeutically. We found that NK diversity is lower at birth than in adults. During an antiviral response to either HIV-1 or West Nile virus, NK diversity increases, resulting in terminal differentiation and cytokine production at the cost of cell division and degranulation. In African women matched for HIV-1 exposure risk, high NK diversity is associated with increased risk of HIV-1 acquisition. Existing diversity may therefore decrease the flexibility of the antiviral response. Collectively, the data reveal that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in forecasting the outcomes of infection and malignancy. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(297):297ra115. DOI:10.1126/scitranslmed.aac5722
  • Science translational medicine 07/2015; 7(297):297ed10. DOI:10.1126/scitranslmed.aab1206
  • Science translational medicine 07/2015; 7(297):297le1. DOI:10.1126/scitranslmed.aab1994
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    ABSTRACT: Degeneration of photoreceptors is a primary cause of vision loss worldwide, making the underlying mechanisms surrounding photoreceptor cell death critical to developing new treatment strategies. Retinal detachment, characterized by the separation of photoreceptors from the underlying retinal pigment epithelium, is a sight-threatening event that can happen in a number of retinal diseases. The detached photoreceptors undergo apoptosis and programmed necrosis. Given that photoreceptors are nondividing cells, their loss leads to irreversible visual impairment even after successful retinal reattachment surgery. To better understand the underlying disease mechanisms, we analyzed innate immune system regulators in the vitreous of human patients with retinal detachment and correlated the results with findings in a mouse model of retinal detachment. We identified the alternative complement pathway as promoting early photoreceptor cell death during retinal detachment. Photoreceptors down-regulate membrane-bound inhibitors of complement, allowing for selective targeting by the alternative complement pathway. When photoreceptors in the detached retina were removed from the primary source of oxygen and nutrients (choroidal vascular bed), the retina became hypoxic, leading to an up-regulation of complement factor B, a key mediator of the alternative pathway. Inhibition of the alternative complement pathway in knockout mice or through pharmacological means ameliorated photoreceptor cell death during retinal detachment. Our current study begins to outline the mechanism by which the alternative complement pathway facilitates photoreceptor cell death in the damaged retina. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(297):297ra116. DOI:10.1126/scitranslmed.aab1482
  • Science translational medicine 07/2015; 7(297):297lr1. DOI:10.1126/scitranslmed.aac9461
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    ABSTRACT: Single-cell sequencing methods are revolutionizing cancer research and medicine by providing powerful tools to investigate intratumor heterogeneity and rare subpopulations. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(296):296fs29. DOI:10.1126/scitranslmed.aac8319
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    ABSTRACT: Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(296):296ra110. DOI:10.1126/scitranslmed.aaa8791
  • Science translational medicine 07/2015; 7(296):296ed9. DOI:10.1126/scitranslmed.aab2404
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    ABSTRACT: Semen parameters are typically used to diagnose male infertility and specify clinical interventions. In idiopathic infertile couples, an unknown male factor could be the cause of infertility even when the semen parameters are normal. Next-generation sequencing of spermatozoal RNAs can provide an objective measure of the paternal contribution and may help guide the care of these couples. We assessed spermatozoal RNAs from 96 couples presenting with idiopathic infertility and identified the final reproductive outcome and sperm RNA elements (SREs) reflective of fecundity status. The absence of required SREs reduced the probability of achieving live birth by timed intercourse or intrauterine insemination from 73 to 27%. However, the absence of these same SREs does not appear to be critical when using assisted reproductive technologies such as in vitro fertilization with or without intracytoplasmic sperm injection. About 30% of the idiopathic infertile couples presented an incomplete set of required SREs, suggesting a male component as the cause of their infertility. Conversely, analysis of couples that failed to achieve a live birth despite presenting with a complete set of SREs suggested that a female factor may have been involved, and this was confirmed by their diagnosis. The data in this study suggest that SRE analysis has the potential to predict the individual success rate of different fertility treatments and reduce the time to achieve live birth. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(295):295re6. DOI:10.1126/scitranslmed.aab1287
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    ABSTRACT: The U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria will succeed only if we alter the definition of "antibiotic." Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(295):295ed8. DOI:10.1126/scitranslmed.aab2373
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    ABSTRACT: Virus-mediated transfer of genes encoding the mechanotransducer channel candidates TMC1 and TMC2 into hair cells of the ear partially restores hearing in animal models of human genetic deafness (Askew et al., this issue). Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(295):295fs28. DOI:10.1126/scitranslmed.aac7545
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    ABSTRACT: Invading pathogens may trigger overactivation of the innate immune system, which results in the release of large amounts of proinflammatory cytokines (cytokine storm) and leads to the development of pulmonary edema, multiorgan failure, and shock. PIAS1 is a multifunctional and potent anti-inflammatory protein that negatively regulates several key inflammatory pathways such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor κB (NF-κB). We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. We also identified a mislocalized HECTD2 polymorphism, HECTD2(A19P), that was present in 8.5% of the population and functioned to reduce inflammation. This polymorphism prevented HECTD2/PIAS1 nuclear interaction, thus preventing PIAS1 degradation. The HECTD2(A19P) polymorphism was also protective toward acute respiratory distress syndrome (ARDS). We then developed a small-molecule inhibitor, BC-1382, that targeted HECTD2 and attenuated lipopolysaccharide (LPS)- and Pseudomonas aeruginosa-induced lung inflammation. These studies describe an unreported innate immune pathway and suggest that mutation or antagonism of the E3 ligase HECTD2 results in reduced severity of lung inflammation by selectively modulating the abundance of the anti-inflammatory protein PIAS1. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(295):295ra109. DOI:10.1126/scitranslmed.aab3881
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    ABSTRACT: Enterovirus infection can cause severe cardiomyopathy in humans. The virus-encoded 2A protease is known to cleave the cytoskeletal protein dystrophin. It is unclear, however, whether cardiomyopathy results from the loss of dystrophin or is due to the emergence of a dominant-negative dystrophin cleavage product. We show for the first time that the 2A protease-mediated carboxyl-terminal dystrophin cleavage fragment (CtermDys) is sufficient to cause marked dystrophic cardiomyopathy. The sarcolemma-localized CtermDys fragment caused myocardial fibrosis, heightened susceptibility to myocardial ischemic injury, and increased mortality during cardiac stress testing in vivo. CtermDys cardiomyopathy was more severe than in hearts completely lacking dystrophin. In vivo titration of CtermDys peptide content revealed an inverse relationship between the decay of membrane-bound CtermDys and the restoration of full-length dystrophin at the sarcolemma, in support of a physiologically relevant loss of dystrophin function in this model. CtermDys gene titration and dystrophin replacement studies further established a target threshold of 50% membrane-bound intact dystrophin necessary to prevent mice from CtermDys cardiomyopathy. Conversely, the NtermDys fragment did not compete with dystrophin and had no pathological effect. Thus, CtermDys must be localized to the sarcolemma, with intact dystrophin <50% of normal levels, to exert dominant-negative peptide-dependent cardiomyopathy. These data support a two-hit dominant-negative disease mechanism where membrane-associated CtermDys severs the link to cortical actin and inhibits both full-length dystrophin and compensatory utrophin from binding at the membrane. Therefore, membrane-bound CtermDys is a new potential translational target for virus-mediated cardiomyopathy. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(294):294ra106. DOI:10.1126/scitranslmed.aaa4804
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    ABSTRACT: Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 07/2015; 7(294):294ra107. DOI:10.1126/scitranslmed.aaa3097
  • Science translational medicine 07/2015; 7(294):294ed7. DOI:10.1126/scitranslmed.aac7112