[Errata] Erratum for the Research Article: "Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with {beta}-blockers" by M. B. Nilsson, H. Sun, L. Diao, P. Tong, D. Liu, L. Li, Y. Fan, A. Poteete, S.-O. Lim, K. Howells, V. Haddad, D. Gomez, H. Tran, G. A. Pena, L. V. Sequist, J. C. Yang, J. Wang, E. S. Kim, R. Herbst, J. J. Lee, W. K. Hong, I. Wistuba, M.-C. Hung, A. K. Sood, J. V. Heymach
(Source: Science Translational Medicine)
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Tags: Errata Source Type: research

[Research Articles] Cardiac glial cells release neurotrophic S100B upon catheter-based treatment of atrial fibrillation
Atrial fibrillation (AF), the most common sustained heart rhythm disorder worldwide, is linked to dysfunction of the intrinsic cardiac autonomic nervous system (ICNS). The role of ICNS damage occurring during catheter-based treatment of AF, which is the therapy of choice for many patients, remains controversial. We show here that the neuronal injury marker S100B is expressed in cardiac glia throughout the ICNS and is released specifically upon catheter ablation of AF. Patients with higher S100B release were more likely to be AF free during follow-up. Subsequent in vitro studies revealed that murine intracardiac neurons rea...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Scherschel, K., Hedenus, K., Jungen, C., Lemoine, M. D., Rübsamen, N., Veldkamp, M. W., Klatt, N., Lindner, D., Westermann, D., Casini, S., Kuklik, P., Eickholt, C., Klöcker, N., Shivkumar, K., Christ, T., Zeller, T., Willems, S., Meyer, C Tags: Research Articles Source Type: research

[Research Articles] Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates
Liver-directed gene therapy for the coagulation disorder hemophilia showed safe and effective results in clinical trials using adeno-associated viral vectors to replace a functional coagulation factor, although some unmet needs remain. Lentiviral vectors (LVs) may address some of these hurdles because of their potential for stable expression and the low prevalence of preexisting viral immunity in humans. However, systemic LV administration to hemophilic dogs was associated to mild acute toxicity and low efficacy at the administered doses. Here, exploiting intravital microscopy and LV surface engineering, we report a major ...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Milani, M., Annoni, A., Moalli, F., Liu, T., Cesana, D., Calabria, A., Bartolaccini, S., Biffi, M., Russo, F., Visigalli, I., Raimondi, A., Patarroyo-White, S., Drager, D., Cristofori, P., Ayuso, E., Montini, E., Peters, R., Iannacone, M., Cantore, A., Na Tags: Research Articles Source Type: research

[Editors' Choice] A sight for sore eyes (or ones with glaucoma)
Transduction of the exoenzyme C3 transferase gene into the trabecular meshwork reduces intraocular pressure in monkeys. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Yadav, V. G. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Waving off neurodegeneration
Gamma wave oscillations provide neuroprotection in mouse models of Alzheimer’s disease. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Neman, J. Tags: Editors ' Choice Source Type: research

[Editors' Choice] T cells iron out tumors
T cells induce tumor cell death through ferroptosis. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Hickman, H. D. Tags: Editors ' Choice Source Type: research

[Reviews] Mouse models of neurodegeneration: Know your question, know your mouse
Many mutant mouse strains have been developed as models to investigate neurodegenerative disease in humans. However, variability in results among studies using these mouse strains has led to questions about the value of these models. Here, we appraise various mouse models for dissecting neurodegenerative disease mechanisms and emphasize the importance of asking appropriate research questions. In therapeutic studies, we suggest that understanding variability among and within mouse models is crucial for preventing translational failures in human patients. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Fisher, E. M. C., Bannerman, D. M. Tags: Reviews Source Type: research

[Research Articles] Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium
The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell–derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells (CPCs), both derived...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Saha, P., Sharma, S., Korutla, L., Datla, S. R., Shoja-Taheri, F., Mishra, R., Bigham, G. E., Sarkar, M., Morales, D., Bittle, G., Gunasekaran, M., Ambastha, C., Arfat, M. Y., Li, D., Habertheuer, A., Hu, R., Platt, M. O., Yang, P., Davis, M. E., Vallabha Tags: Research Articles Source Type: research

[Research Articles] Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection
Sustained viremia after acute HIV infection is associated with profound CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer+) CD8+ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposur...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Ndhlovu, Z. M., Kazer, S. W., Nkosi, T., Ogunshola, F., Muema, D. M., Anmole, G., Swann, S. A., Moodley, A., Dong, K., Reddy, T., Brockman, M. A., Shalek, A. K., Ndungu, T., Walker, B. D. Tags: Research Articles Source Type: research

[Research Articles] Primary cilia defects causing mitral valve prolapse
Mitral valve prolapse (MVP) affects 1 in 40 people and is the most common indication for mitral valve surgery. MVP can cause arrhythmias, heart failure, and sudden cardiac death, and to date, the causes of this disease are poorly understood. We now demonstrate that defects in primary cilia genes and their regulated pathways can cause MVP in familial and sporadic nonsyndromic MVP cases. Our expression studies and genetic ablation experiments confirmed a role for primary cilia in regulating ECM deposition during cardiac development. Loss of primary cilia during development resulted in progressive myxomatous degeneration and ...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Toomer, K. A., Yu, M., Fulmer, D., Guo, L., Moore, K. S., Moore, R., Drayton, K. D., Glover, J., Peterson, N., Ramos-Ortiz, S., Drohan, A., Catching, B. J., Stairley, R., Wessels, A., Lipschutz, J. H., Delling, F. N., Jeunemaitre, X., Dina, C., Collins, R Tags: Research Articles Source Type: research

[Reviews] Advances in therapeutic applications of extracellular vesicles
Extracellular vesicles (EVs) are nanometer-sized, lipid membrane–enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents. EVs can potentiate tissue regeneration, participate in immune modulation, and function as potential alternatives to stem cell therapy, and bi...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Wiklander, O. P. B., Brennan, M. A., Lötvall, J., Breakefield, X. O., EL Andaloussi, S. Tags: Reviews Source Type: research

[Research Articles] Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition
Sebum plays important physiological roles in human skin. Excess sebum production contributes to the pathogenesis of acne vulgaris, and suppression of sebum production reduces acne incidence and severity. We demonstrate that sebum production in humans depends on local flux through the de novo lipogenesis (DNL) pathway within the sebocyte. About 80 to 85% of sebum palmitate (16:0) and sapienate (16:1n10) were derived from DNL, based on stable isotope labeling, much higher than the contribution of DNL to triglyceride palmitate in circulation (~20%), indicating a minor contribution by nonskin sources to sebum lipids. This depe...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Esler, W. P., Tesz, G. J., Hellerstein, M. K., Beysen, C., Sivamani, R., Turner, S. M., Watkins, S. M., Amor, P. A., Carvajal-Gonzalez, S., Geoly, F. J., Biddle, K. E., Purkal, J. J., Fitch, M., Buckeridge, C., Silvia, A. M., Griffith, D. A., Gorgoglione, Tags: Research Articles Source Type: research

[Editors' Choice] Mind the gap: Cx32 and {alpha}-synuclein
α-synuclein oligomer uptake by neurons and oligodendrocytes exploits connexin-32. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Haigh, C. Tags: Editors ' Choice Source Type: research

[Research Articles] Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina
Retinal gene therapy with adeno-associated viral (AAV) vectors holds promises for treating inherited and noninherited diseases of the eye. Although clinical data suggest that retinal gene therapy is safe and effective, delivery of large genes is hindered by the limited AAV cargo capacity. Protein trans-splicing mediated by split inteins is used by single-cell organisms to reconstitute proteins. Here, we show that delivery of multiple AAV vectors each encoding one of the fragments of target proteins flanked by short split inteins results in protein trans-splicing and full-length protein reconstitution in the retina of mice ...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Tornabene, P., Trapani, I., Minopoli, R., Centrulo, M., Lupo, M., de Simone, S., Tiberi, P., DellAquila, F., Marrocco, E., Iodice, C., Iuliano, A., Gesualdo, C., Rossi, S., Giaquinto, L., Albert, S., Hoyng, C. B., Polishchuk, E., Cremers, F. P. M., Surace Tags: Research Articles Source Type: research

[Research Articles] Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51
We report here that cediranib confers sensitivity to olaparib by down-regulating HDR in tumor cells. This occurs partially as a result of cediranib inducing hypoxia, which suppresses expression of the HDR factors BRCA1/2 and RAD51 recombinase (RAD51). However, we also observed that cediranib has a direct effect on HDR independent of its ability to induce tumor hypoxia. This direct effect occurs through platelet-derived growth factor receptor (PDGFR) inhibition, activation of protein phosphatase 2A (PP2A), and E2F transcription factor 4 (E2F4)/RB transcriptional corepressor like 2 (RB2/p130)–mediated repression of BRC...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Kaplan, A. R., Gueble, S. E., Liu, Y., Oeck, S., Kim, H., Yun, Z., Glazer, P. M. Tags: Research Articles Source Type: research

[Research Articles] A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates
Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Monovalent VLPs elicited neutralizing antibody responses and protected mice and nonhuman primates (...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Ko, S.-Y., Akahata, W., Yang, E. S., Kong, W.-P., Burke, C. W., Honnold, S. P., Nichols, D. K., Huang, Y.-J. S., Schieber, G. L., Carlton, K., DaSilva, L., Traina-Dorge, V., Vanlandingham, D. L., Tsybovsky, Y., Stephens, T., Baxa, U., Higgs, S., Roy, C. J Tags: Research Articles Source Type: research

[Editors' Choice] CuRBing cancers enthusiasm
A gene expression signature of biallelic RB1 loss identifies more aggressive tumors. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Sowalsky, A. G. Tags: Editors ' Choice Source Type: research

[Editors' Choice] SHANK3 puts autism to sleep
Mutation of autism-associated gene SHANK3 leads to sleep problems in mice and humans. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Osterweil, E. K. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Organs-on-chips take baby steps
Two organ-on-chip devices enable investigation of cellular interactions in human fetal membranes in vitro. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: McCain, M. L. Tags: Editors ' Choice Source Type: research

[Research Articles] Detecting middle ear fluid using smartphones
We present an accessible solution that uses speakers and microphones within existing smartphones to detect middle ear fluid by assessing eardrum mobility. We conducted a clinical study on 98 patient ears at a pediatric surgical center. Using leave-one-out cross-validation to estimate performance on unseen data, we obtained an area under the curve (AUC) of 0.898 for the smartphone-based machine learning algorithm. In comparison, commercial acoustic reflectometry, which requires custom hardware, achieved an AUC of 0.776. Furthermore, we achieved 85% sensitivity and 82% specificity, comparable to published performance measure...
Source: Science Translational Medicine - May 15, 2019 Category: Biomedical Science Authors: Chan, J., Raju, S., Nandakumar, R., Bly, R., Gollakota, S. Tags: Research Articles Source Type: research

[Research Articles] HBEGF+ macrophages in rheumatoid arthritis induce fibroblast invasiveness
Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF+ inflammatory macrophages is enriched in RA tissues and is shaped by resident fibroblasts and the cytokine tumor necrosis factor (TNF). These macrophages promoted fibroblast invasiveness in an e...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Kuo, D., Ding, J., Cohn, I. S., Zhang, F., Wei, K., Rao, D. A., Rozo, C., Sokhi, U. K., Shanaj, S., Oliver, D. J., Echeverria, A. P., DiCarlo, E. F., Brenner, M. B., Bykerk, V. P., Goodman, S. M., Raychaudhuri, S., Rätsch, G., Ivashkiv, L. B., Don Tags: Research Articles Source Type: research

[Editors' Choice] GALvanizing Alzheimers disease therapy to combat the inflamed brain
Galectin-3 is elevated in patients with Alzheimer’s disease (AD), and its deletion reduces neuroinflammation and β-amyloid burden in a mouse model of AD. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Abalde-Atristain, L. Tags: Editors ' Choice Source Type: research

[Research Articles] A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder
There are no approved pharmacological therapies to address the core symptoms of autism spectrum disorder (ASD), namely, persistent deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behaviors, interests, or activities. The neuropeptide vasopressin has been implicated in the regulation of social behaviors, and its modulation has emerged as a therapeutic target for ASD. The phase 2 VANILLA clinical trial reported here evaluated balovaptan, an orally administered selective vasopressin V1a receptor antagonist, in 223 men with ASD and intelligence quotient ≥70. The ...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Bolognani, F., del Valle Rubido, M., Squassante, L., Wandel, C., Derks, M., Murtagh, L., Sevigny, J., Khwaja, O., Umbricht, D., Fontoura, P. Tags: Research Articles Source Type: research

[Research Articles] A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism
The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 Inte...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Parker, K. J., Oztan, O., Libove, R. A., Mohsin, N., Karhson, D. S., Sumiyoshi, R. D., Summers, J. E., Hinman, K. E., Motonaga, K. S., Phillips, J. M., Carson, D. S., Fung, L. K., Garner, J. P., Hardan, A. Y. Tags: Research Articles Source Type: research

[Focus] Tinkering with the vasopressin pathway in autism
Two clinical trials targeting the vasopressin pathway in autism highlight continuing challenges in outcome measures and statistical power. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Forgeot dArc, B., Mottron, L., Elsabbagh, M., Jacquemont, S. Tags: Focus Source Type: research

[Editors' Choice] And the MVP award goes to: Major vault protein
MVP functions as an endogenous suppressor of NF-B and regulates obesity-associated metabolic disease. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Ozcan, L. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Dual oncogene excision is greater than the sum of its parts
Ablation of EGFR and c-RAF in combination is effective against aggressive pancreatic tumors. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Montero, J. Tags: Editors ' Choice Source Type: research

[Research Articles] Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections
Parasitic filarial nematodes cause debilitating infections in people in resource-limited countries. A clinically validated approach to eliminating worms uses a 4- to 6-week course of doxycycline that targets Wolbachia, a bacterial endosymbiont required for worm viability and reproduction. However, the prolonged length of therapy and contraindication in children and pregnant women have slowed adoption of this treatment. Here, we describe discovery and optimization of quinazolines CBR417 and CBR490 that, with a single dose, achieve>99% elimination of Wolbachia in the in vivo Litomosoides sigmodontis filarial infection mod...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Bakowski, M. A., Shiroodi, R. K., Liu, R., Olejniczak, J., Yang, B., Gagaring, K., Guo, H., White, P. M., Chappell, L., Debec, A., Landmann, F., Dubben, B., Lenz, F., Struever, D., Ehrens, A., Frohberger, S. J., Sjoberg, H., Pionnier, N., Murphy, E., Arch Tags: Research Articles Source Type: research

[Research Articles] TGF-{beta} type 2 receptor-mediated modulation of the IL-36 family can be therapeutically targeted in osteoarthritis
Mechanisms that govern the shift from joint homeostasis to osteoarthritis (OA) remain unknown. Here, we identify a pathway used for joint development and homeostasis, and its role in OA. Using a combination of transgenic, pharmacological, and surgical conditions in mouse and human tissues, we found that TGF-β signaling promotes joint homeostasis through regulation of the IL-36 family. We identified IL-36 receptor antagonist (IL-36 in mice and IL-36RN in humans) as a potential disease-modifying OA drug. Specifically, OA development was associated with IL-36α up-regulation and IL-36Ra down-regulation in mice with ...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Li, T., Chubinskaya, S., Esposito, A., Jin, X., Tagliafierro, L., Loeser, R., Hakimiyan, A. A., Longobardi, L., Ozkan, H., Spagnoli, A. Tags: Research Articles Source Type: research

[Research Articles] Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma
Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomic analyses of clinical specimens, we show that metabolic reprogramming toward oxidative phosphorylation (OXPHOS) and glutaminolysis is associated with therapeutic resistance to the Bruton’s tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma (MCL), a B cell lymphoma subtype with poor clinical outcomes. Inhibition o...
Source: Science Translational Medicine - May 8, 2019 Category: Biomedical Science Authors: Zhang, L., Yao, Y., Zhang, S., Liu, Y., Guo, H., Ahmed, M., Bell, T., Zhang, H., Han, G., Lorence, E., Badillo, M., Zhou, S., Sun, Y., Di Francesco, M. E., Feng, N., Haun, R., Lan, R., Mackintosh, S. G., Mao, X., Song, X., Zhang, J., Pham, L. V., Lorenzi, Tags: Research Articles Source Type: research

[Research Resources] A{beta} and tau prion-like activities decline with longevity in the Alzheimers disease human brain
The hallmarks of Alzheimer’s disease (AD) are the accumulation of Aβ plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney–293T cells to quantify intracellular self-propagating conformers of Aβ in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological Aβ conformers. Individuals over 80 years of age had the lowest amounts of prion-like Aβ and phosphorylated tau. Unexpectedly, the longevity-dependent decrea...
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Aoyagi, A., Condello, C., Stöhr, J., Yue, W., Rivera, B. M., Lee, J. C., Woerman, A. L., Halliday, G., van Duinen, S., Ingelsson, M., Lannfelt, L., Graff, C., Bird, T. D., Keene, C. D., Seeley, W. W., DeGrado, W. F., Prusiner, S. B. Tags: Research Resources Source Type: research

[Research Articles] Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis
Colonization of the skin by Staphylococcus aureus is associated with exacerbation of atopic dermatitis (AD), but any direct mechanism through which dysbiosis of the skin microbiome may influence the development of AD is unknown. Here, we show that proteases and phenol-soluble modulin α (PSMα) secreted by S. aureus lead to endogenous epidermal proteolysis and skin barrier damage that promoted inflammation in mice. We further show that clinical isolates of different coagulase-negative staphylococci (CoNS) species residing on normal skin produced autoinducing peptides that inhibited the S. aureus agr system, in tu...
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Williams, M. R., Costa, S. K., Zaramela, L. S., Khalil, S., Todd, D. A., Winter, H. L., Sanford, J. A., ONeill, A. M., Liggins, M. C., Nakatsuji, T., Cech, N. B., Cheung, A. L., Zengler, K., Horswill, A. R., Gallo, R. L. Tags: Research Articles Source Type: research

[Editors' Choice] Erratum for the Research Article: "Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation" by R. D. Kirkton, M. Santiago-Maysonet, J. H. Lawson, W. E. Tente, S. L. M. Dahl, L. E. Niklason, H. L. Prichard
(Source: Science Translational Medicine)
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Tags: Editors ' Choice Source Type: research

[Research Articles] Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction
Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf mate...
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Li, X., Cho, B., Martin, R., Seu, M., Zhang, C., Zhou, Z., Choi, J. S., Jiang, X., Chen, L., Walia, G., Yan, J., Callanan, M., Liu, H., Colbert, K., Morrissette-McAlmon, J., Grayson, W., Reddy, S., Sacks, J. M., Mao, H.-Q. Tags: Research Articles Source Type: research

[Research Articles] Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects
Interference with immune cell proliferation represents a successful treatment strategy in T cell–mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS). In a preclinical antige...
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Klotz, L., Eschborn, M., Lindner, M., Liebmann, M., Herold, M., Janoschka, C., Torres Garrido, B., Schulte-Mecklenbeck, A., Gross, C. C., Breuer, J., Hundehege, P., Posevitz, V., Pignolet, B., Nebel, G., Glander, S., Freise, N., Austermann, J., Wirth, T., Tags: Research Articles Source Type: research

[Editors' Choice] Somatic mutations are improving their bad rap
Recurrent somatic mutations could help protect the liver from injury. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Naxerova, K. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Fabricating a new heart: One step closer to reality
Cardiomyocytes and endothelial cells printed in omentum-derived hydrogels generate perfusable thick heart tissue that can be implanted in rodents. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Han, L.-H. Tags: Editors ' Choice Source Type: research

[Research Articles] Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome
Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak at term, are sustained after delivery, and might synergize with previously defined signaling pathways implicated in aneurysm progression, we examined the hormone oxytocin, which initiates uterine contraction and milk letdown for the duration of lactation through phosphorylation of extracellular signal–r...
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Habashi, J. P., MacFarlane, E. G., Bagirzadeh, R., Bowen, C., Huso, N., Chen, Y., Bedja, D., Creamer, T. J., Rykiel, G., Manning, M., Huso, D., Dietz, H. C. Tags: Research Articles Source Type: research

[Focus] Exacting Edward Jenners revenge: The quest for a new tuberculosis vaccine
Recent experimental and clinical work has reinvigorated the pursuit of a better tuberculosis vaccine. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Porcelli, S. A., Jacobs, W. R. Tags: Focus Source Type: research

[Editors' Choice] Neurogenesis takes a hit in Alzheimers disease
New neurons are born in healthy humans throughout aging but decline in Alzheimer's disease, linking a loss of neurogenesis with disease progression. (Source: Science Translational Medicine)
Source: Science Translational Medicine - May 1, 2019 Category: Biomedical Science Authors: Gallardo, G. Tags: Editors ' Choice Source Type: research

[Research Articles] Chronic hypoxia-induced Cirbp hypermethylation attenuates hypothermic cardioprotection via down-regulation of ubiquinone biosynthesis
This study tested whether CH attenuates hypothermic cardioprotection during CPB. Using a rat model of CPB, we found that hypothermic cardioprotection was impaired in CH rats but was preserved in normoxic rats. Cardiac proteomes showed that cold-inducible RNA binding protein (CIRBP) was significantly (P = 0.03) decreased in CH rats during CPB. Methylation analysis of neonatal rat cardiomyocytes under CH and myocardium specimens from patients with CH showed that CH induced hypermethylation of the Cirbp promoter region, resulting in its depression and failure to respond to cold stress. Cirbp-knockout rats showed attenuated hy...
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Liu, Y., Xing, J., Li, Y., Luo, Q., Su, Z., Zhang, X., Zhang, H. Tags: Research Articles Source Type: research

[Research Articles] A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity
The CD40/CD40L axis plays a central role in the generation of humoral immune responses and is an attractive target for treating autoimmune diseases in the clinic. Here, we report the generation and clinical results of a CD40L binding protein, VIB4920, which lacks an Fc domain, therefore avoiding platelet-related safety issues observed with earlier monoclonal antibody therapeutics that targeted CD40L. VIB4920 blocked downstream CD40 signaling events, resulting in inhibition of human B cell activation and plasma cell differentiation, and did not induce platelet aggregation in preclinical studies. In a phase 1 study in health...
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Karnell, J. L., Albulescu, M., Drabic, S., Wang, L., Moate, R., Baca, M., Oganesyan, V., Gunsior, M., Thisted, T., Yan, L., Li, J., Xiong, X., Eck, S. C., de los Reyes, M., Yusuf, I., Streicher, K., Müller-Ladner, U., Howe, D., Ettinger, R., Herbs Tags: Research Articles Source Type: research

[Research Articles] Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation
We describe a platform for population-scale, provisional diagnosis of genetic diseases with automated phenotyping and interpretation. Genome sequencing was expedited by bead-based genome library preparation directly from blood samples and sequencing of paired 100-nt reads in 15.5 hours. Clinical natural language processing (CNLP) automatically extracted children’s deep phenomes from electronic health records with 80% precision and 93% recall. In 101 children with 105 genetic diseases, a mean of 4.3 CNLP-extracted phenotypic features matched the expected phenotypic features of those diseases, compared with a match of ...
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Clark, M. M., Hildreth, A., Batalov, S., Ding, Y., Chowdhury, S., Watkins, K., Ellsworth, K., Camp, B., Kint, C. I., Yacoubian, C., Farnaes, L., Bainbridge, M. N., Beebe, C., Braun, J. J. A., Bray, M., Carroll, J., Cakici, J. A., Caylor, S. A., Clarke, C. Tags: Research Articles Source Type: research

[Research Articles] A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix
Bone morphogenetic protein (BMP)/carriers approved for orthopedic procedures achieve efficacy superior or equivalent to autograft bone. However, required supraphysiological BMP concentrations have been associated with potential local and systemic adverse events. Suboptimal BMP/receptor binding and rapid BMP release from approved carriers may contribute to these outcomes. To address these issues and improve efficacy, we engineered chimeras with increased receptor binding by substituting BMP-6 and activin A receptor binding domains into BMP-2 and optimized a carrier for chimera retention and tissue ingrowth. BV-265, a BMP-2/...
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Seeherman, H. J., Berasi, S. P., Brown, C. T., Martinez, R. X., Juo, Z. S., Jelinsky, S., Cain, M. J., Grode, J., Tumelty, K. E., Bohner, M., Grinberg, O., Orr, N., Shoseyov, O., Eyckmans, J., Chen, C., Morales, P. R., Wilson, C. G., Vanderploeg, E. J., W Tags: Research Articles Source Type: research

[Editorial] A decade of Science Translational Medicine
In this Editorial, co-Chief Scientific Advisors of Science Translational Medicine, Elazer Edelman and Garret FitzGerald, discuss challenges and opportunities for the next decade of translational research. (Source: Science Translational Medicine)
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Edelman, E. R., FitzGerald, G. A. Tags: Editorial Source Type: research

[Editors' Choice] Transcriptional adaptation: Another reason why your disease model fails you
Up-regulation of paralogous transcripts is a potential mechanism of genetic compensation. (Source: Science Translational Medicine)
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Ronzitti, G. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Continuously capturing circulating cancer cells
A wearable apheresis device allows for continuous and specific capture of circulating tumor cells. (Source: Science Translational Medicine)
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Kulkarni, R. P. Tags: Editors ' Choice Source Type: research

[Editors' Choice] A vaccine to kiss EBV goodbye
A nanoparticle Epstein-Barr virus glycoprotein gH/gL vaccine elicits antibodies that mediate cell type–independent protection from infection. (Source: Science Translational Medicine)
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Boyle, M. Tags: Editors ' Choice Source Type: research

[Research Articles] The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans
The short-chain fatty acid propionate is a potent inhibitor of molds that is widely used as a food preservative and endogenously produced by gut microbiota. Although generally recognized as safe by the U.S. Food and Drug Administration, the metabolic effects of propionate consumption in humans are unclear. Here, we report that propionate stimulates glycogenolysis and hyperglycemia in mice by increasing plasma concentrations of glucagon and fatty acid–binding protein 4 (FABP4). Fabp4-deficient mice and mice lacking liver glucagon receptor were protected from the effects of propionate. Although propionate did not direc...
Source: Science Translational Medicine - April 24, 2019 Category: Biomedical Science Authors: Tirosh, A., Calay, E. S., Tuncman, G., Claiborn, K. C., Inouye, K. E., Eguchi, K., Alcala, M., Rathaus, M., Hollander, K. S., Ron, I., Livne, R., Heianza, Y., Qi, L., Shai, I., Garg, R., Hotamisligil, G. S. Tags: Research Articles Source Type: research

[Research Articles] Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis
Filamentous bacteriophage (Pf phage) contribute to the virulence of Pseudomonas aeruginosa infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.5% (n = 9) were consistently Pf phage positive. In the second cohort, a prospective cross-sectional cohort of 58 patients with CF at Stanford, sputum qPCR analysis showed that 36.2% (...
Source: Science Translational Medicine - April 17, 2019 Category: Biomedical Science Authors: Burgener, E. B., Sweere, J. M., Bach, M. S., Secor, P. R., Haddock, N., Jennings, L. K., Marvig, R. L., Johansen, H. K., Rossi, E., Cao, X., Tian, L., Nedelec, L., Molin, S., Bollyky, P. L., Milla, C. E. Tags: Research Articles Source Type: research