[Technical Comments] Response to comment on "ALK is a therapeutic target for lethal sepsis"
ALK inhibitors may exhibit STING-independent anti-inflammatory activity in macrophages and monocytes. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Tang, D., Kang, R. Tags: Technical Comments Source Type: research

[Focus] Big data and black-box medical algorithms
New machine-learning techniques entering medicine present challenges in validation, regulation, and integration into practice. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Price, W. N. Tags: Focus Source Type: research

[Technical Comments] Comment on "ALK is a therapeutic target for lethal sepsis"
Physiologically relevant ALK (anaplastic lymphoma kinase) expression was not detected in human and mouse monocytes and macrophages, suggesting that the effects of bioactive compounds on stimulator of interferon genes (STING) activation may not depend on ALK. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Blasco, R. B., Patrucco, E., Mota, I., Tai, W.-T., Chiarle, R. Tags: Technical Comments Source Type: research

[Retraction] Editorial retraction
(Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Berg, J. M., Smith, O. M. Tags: Retraction Source Type: research

[Research Articles] A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases
Hemorrhagic fever outbreaks such as Ebola are difficult to detect and control because of the lack of low-cost, easily deployable diagnostics and because initial clinical symptoms mimic other endemic diseases such as malaria. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need. Although rapid tests such as lateral flow can be broadly deployed, they are typically not well-suited for differentiating among multiple diseases presenting with similar symptoms. Early detection and control of Ebola outbreaks requir...
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Sebba, D., Lastovich, A. G., Kuroda, M., Fallows, E., Johnson, J., Ahouidi, A., Honko, A. N., Fu, H., Nielson, R., Carruthers, E., Diedhiou, C., Ahmadou, D., Soropogui, B., Ruedas, J., Peters, K., Bartkowiak, M., Magassouba, N., Mboup, S., Amor, Y. B., Co Tags: Research Articles Source Type: research

[Editors' Choice] The brain carries a lot of weight
Researchers used neuroimaging to show that the best predictor of successful weight loss was greater brain activity in prefrontal areas in the brain involved in self-control. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Page, K. A. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Drug delivery in stealth mode
Zwitterionic polypeptides with high chemical specificity and "stealth"-like behavior have superior pharmacokinetics compared with uncharged polypeptides in mice. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Holloway, J. L. Tags: Editors ' Choice Source Type: research

[Editors' Choice] T cell receptors communicate by movement
Dynamic structural changes in the α chain transmembrane region convey T cell receptor signals. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Hinrichs, C. S. Tags: Editors ' Choice Source Type: research

[Research Articles] MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation
Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in dela...
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Bommareddy, P. K., Aspromonte, S., Zloza, A., Rabkin, S. D., Kaufman, H. L. Tags: Research Articles Source Type: research

[Research Articles] Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal ...
Source: Science Translational Medicine - December 12, 2018 Category: Biomedical Science Authors: Nino, D. F., Zhou, Q., Yamaguchi, Y., Martin, L. Y., Wang, S., Fulton, W. B., Jia, H., Lu, P., Prindle, T., Zhang, F., Crawford, J., Hou, Z., Mori, S., Chen, L. L., Guajardo, A., Fatemi, A., Pletnikov, M., Kannan, R. M., Kannan, S., Sodhi, C. P., Hackam, Tags: Research Articles Source Type: research

[Research Articles] Noncoding regions are the main source of targetable tumor-specific antigens
In conclusion, the strategy reported herein could considerably facilitate the identification and prioritization of actionable human TSAs. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Laumont, C. M., Vincent, K., Hesnard, L., Audemard, E., Bonneil, E., Laverdure, J.-P., Gendron, P., Courcelles, M., Hardy, M.-P., Cote, C., Durette, C., St-Pierre, C., Benhammadi, M., Lanoix, J., Vobecky, S., Haddad, E., Lemieux, S., Thibault, P., Perreau Tags: Research Articles Source Type: research

[Research Articles] A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis
Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 and cause familial amyotrophic lateral sclerosis (FALS). However, the implications of wild-type SOD1 misfolding in sporadic forms of ALS (SALS) remain unclear. By screening human memory B cells from a large cohort of healthy elderly subjects, we generated a recombinant human monoclonal antibody (α-miSOD1) that selectively bound to misfolded SOD1, but not to physiological SOD1 dimers. On postmortem spinal cord sections from 121 patients with ALS, α-miSOD1 antibody identified misfolded SOD1 in a majority of cas...
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Maier, M., Welt, T., Wirth, F., Montrasio, F., Preisig, D., McAfoose, J., Vieira, F. G., Kulic, L., Späni, C., Stehle, T., Perrin, S., Weber, M., Hock, C., Nitsch, R. M., Grimm, J. Tags: Research Articles Source Type: research

[Research Articles] Wireless, battery-free, flexible, miniaturized dosimeters monitor exposure to solar radiation and to light for phototherapy
We present optical metrology approaches, optoelectronic designs, and wireless modes of operation that serve as the basis for miniature, low-cost, and battery-free devices for precise dosimetry at multiple wavelengths. These platforms use a system on a chip with near-field communication functionality, a radio frequency antenna, photodiodes, supercapacitors, and a transistor to exploit a continuous accumulation mechanism for measurement. Experimental and computational studies of the individual components, the collective systems, and the performance parameters highlight the operating principles and design considerations. Eval...
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Heo, S. Y., Kim, J., Gutruf, P., Banks, A., Wei, P., Pielak, R., Balooch, G., Shi, Y., Araki, H., Rollo, D., Gaede, C., Patel, M., Kwak, J. W., Pena-Alcantara, A. E., Lee, K.-T., Yun, Y., Robinson, J. K., Xu, S., Rogers, J. A. Tags: Research Articles Source Type: research

[Research Articles] Noninvasive 11C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis
In this study, we developed a multidrug treatment model in rabbits with experimentally induced TBM and performed serial noninvasive dynamic 11C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spectrometry. We demonstrate that rifampin penetration into infected brain lesions is limited, spatially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. First-in-human 11C-rifampin PE...
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Tucker, E. W., Guglieri-Lopez, B., Ordonez, A. A., Ritchie, B., Klunk, M. H., Sharma, R., Chang, Y. S., Sanchez-Bautista, J., Frey, S., Lodge, M. A., Rowe, S. P., Holt, D. P., Gobburu, J. V. S., Peloquin, C. A., Mathews, W. B., Dannals, R. F., Pardo, C. A Tags: Research Articles Source Type: research

[Errata] Erratum for the Research Article: "Engineering a highly elastic human protein-based sealant for surgical applications" by N. Annabi, Y.-N. Zhang, A. Assmann, E. S. Sani, G. Cheng, A. D. Lassaletta, A. Vegh, B. Dehghani, G. U. Ruiz-Esparza, X. Wang, S. Gangadharan, A. S. Weiss, A. Khademhosseini
(Source: Science Translational Medicine)
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Tags: Errata Source Type: research

[Editors' Choice] The virtue of tolerance
A chromatin-inspired nanodrug suppresses undesired immune responses. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Shen, K. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Magnets make target cells more attractive to CRISPR
Local CRISPR-Cas9–mediated genome editing using magnetic nanoparticles complexed with recombinant baculoviral vectors minimizes genotoxicity. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Nance, E. A. Tags: Editors ' Choice Source Type: research

[Editors' Choice] A high five for TB screening
Whole-blood transcriptional profiling identifies a five-gene signature for tuberculosis screening among people living with HIV. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 5, 2018 Category: Biomedical Science Authors: Langelier, C. Tags: Editors ' Choice Source Type: research

[Editors' Choice] The two immune sides of obesity
Obesity promotes PD-1–mediated T cell dysfunction but also improves tumor response to immune checkpoint blockade. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Lujambio, A. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Decoding the mood network
Machine learning and intracranial electroencephalography recordings reveal a circuit mechanism encoding mood state fluctuations over time. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Liston, C. Tags: Editors ' Choice Source Type: research

[Editors' Choice] DNA folding for renal rescue
DNA origami nanostructures offer an alternative therapeutic for kidney targeting and treatment of acute kidney injury in mice. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Conway, C. Tags: Editors ' Choice Source Type: research

[Research Articles] Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis
Osteoarthritis is a debilitating joint disease affecting nearly 30 million people for which there are no disease-modifying therapies. Several drugs that have failed clinical trials have shown inefficient and inadequate delivery to target cells. Anabolic growth factors are one class of such drugs that could be disease-modifying if delivered directly to chondrocytes, which reside deep within dense, anionic cartilage tissue. To overcome this biological barrier, we conjugated a growth factor to a cationic nanocarrier for targeted delivery to chondrocytes and retention within joint cartilage after direct intra-articular injecti...
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Geiger, B. C., Wang, S., Padera, R. F., Grodzinsky, A. J., Hammond, P. T. Tags: Research Articles Source Type: research

[Research Articles] Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF-licensed myeloid cells
Allogeneic hematopoietic cell transplantation (allo-HCT) not only is an effective treatment for several hematologic malignancies but can also result in potentially life-threatening graft-versus-host disease (GvHD). GvHD is caused by T cells within the allograft attacking nonmalignant host tissues; however, these same T cells mediate the therapeutic graft-versus-leukemia (GvL) response. Thus, there is an urgent need to understand how to mechanistically uncouple GvL from GvHD. Using preclinical models of full and partial MHC-mismatched HCT, we here show that the granulocyte-macrophage colony-stimulating factor (GM-CSF) produ...
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Tugues, S., Amorim, A., Spath, S., Martin-Blondel, G., Schreiner, B., De Feo, D., Lutz, M., Guscetti, F., Apostolova, P., Haftmann, C., Hasselblatt, P., Nunez, N. G., Hottiger, M. O., van den Broek, M., Manz, M. G., Zeiser, R., Becher, B. Tags: Research Articles Source Type: research

[Focus] Catering to chondrocytes
An innovative strategy for delivering drugs to chondrocytes in situ offers new avenues for treating osteoarthritis (Geiger et al., this issue). (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Evans, C. H. Tags: Focus Source Type: research

[Research Articles] Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers
Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical and infectious morbidity. The primary molecular chain of events leading to the initiation of adhesions has been elusive, chiefly due to the lack of an identifiable cell of origin. Using clonal analysis and lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) and mesothelin (MSLN) as a primary instigator of peritoneal adhesions after surgery in mice. We demonstrate that an anti-MSLN antibody diminished adhesion formation in a mouse model where adhe...
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Tsai, J. M., Sinha, R., Seita, J., Fernhoff, N., Christ, S., Koopmans, T., Krampitz, G. W., McKenna, K. M., Xing, L., Sandholzer, M., Sales, J. H., Shoham, M., McCracken, M., Joubert, L.-M., Gordon, S. R., Poux, N., Wernig, G., Norton, J. A., Weissman, I. Tags: Research Articles Source Type: research

[Research Articles] Gene therapy reduces Parkinsons disease symptoms by reorganizing functional brain connectivity
Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson’s disease (PD). A phase 2 clinical trial showed that delivering glutamic acid decarboxylase (GAD) into the subthalamic nucleus (STN) of patients with PD had therapeutic effects. To determine the mechanism underlying this response, we analyzed metabolic imaging data from patients who received gene therapy and those randomized to sham surgery, all of whom had been scanned preoperatively and at 6 and 12 months after surgery. Those who received GAD gene therapy developed a unique treatment-dependent polysynaptic brai...
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Authors: Niethammer, M., Tang, C. C., Vo, A., Nguyen, N., Spetsieris, P., Dhawan, V., Ma, Y., Small, M., Feigin, A., During, M. J., Kaplitt, M. G., Eidelberg, D. Tags: Research Articles Source Type: research

[Errata] Erratum for the Research Article: "Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy" by X. Gao, N. Ran, X. Dong, B. Zuo, R. Yang, Q. Zhou, H. M. Moulton, Y. Seow, H. Yin
(Source: Science Translational Medicine)
Source: Science Translational Medicine - November 28, 2018 Category: Biomedical Science Tags: Errata Source Type: research

[Errata] Erratum for the Research Article: "The ERBB network facilitates KRAS-driven lung tumorigenesis" by B. Kruspig, T. Monteverde, S. Neidler, A. Hock, E. Kerr, C. Nixon, W. Clark, A. Hedley, S. Laing, S. B. Coffelt, J. Le Quesne, C. Dick, K. Vousden, C. P. Martins, D. J. Murphy
(Source: Science Translational Medicine)
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Tags: Errata Source Type: research

[Editors' Choice] Noncanonical DNA modification revealed in glioblastoma
ALKBH1 promotes glioblastoma by controlling the N6-methyladenine DNA modification on hypoxia response genes. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Zhang, Q. Tags: Editors ' Choice Source Type: research

[Editors' Choice] 10,368 first dates: Microfluidic T cell matchmaking
Coencapsulation of T cells and target cells into arrays of subnanoliter droplets improves the identification of functional T cell receptors. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Au, S. H. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Not just uninhibited: Interneurons and seizure onset
Optogenetic study in vivo demonstrates that different types of interneurons show consistently elevated but distinct firing patterns in the period preceding seizure onset in a rodent model of epilepsy. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Andreae, L. C. Tags: Editors ' Choice Source Type: research

[Research Articles] Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo
In this study, we screened 27 ANDV convalescent HCPS patient sera for their capacity to bind and neutralize ANDV in vitro. One patient who showed high neutralizing titer was selected to isolate ANDV–glycoprotein (GP) Abs. ANDV-GP–specific memory B cells were single cell sorted, and recombinant immunoglobulin G antibodies were cloned and produced. Two monoclonal Abs (mAbs), JL16 and MIB22, potently recognized ANDV-GPs and neutralized ANDV. We examined the post-exposure efficacy of these two mAbs as a monotherapy or in combination therapy in a Syrian hamster model of ANDV-induced HCPS, and both mAbs protected 100...
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Garrido, J. L., Presscott, J., Calvo, M., Bravo, F., Alvarez, R., Salas, A., Riquelme, R., Rioseco, M. L., Williamson, B. N., Haddock, E., Feldmann, H., Barria, M. I. Tags: Research Articles Source Type: research

[Research Articles] Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma
Preclinical and clinical evidence indicates that a subset of asthma is driven by type 2 cytokines such as interleukin-4 (IL-4), IL-5, IL-9, and IL-13. Additional evidence predicts pathogenic roles for IL-6 and type I and type II interferons. Because each of these cytokines depends on Janus kinase 1 (JAK1) for signal transduction, and because many of the asthma-related effects of these cytokines manifest in the lung, we hypothesized that lung-restricted JAK1 inhibition may confer therapeutic benefit. To test this idea, we synthesized iJak-381, an inhalable small molecule specifically designed for local JAK1 inhibition in th...
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Dengler, H. S., Wu, X., Peng, I., Rinderknecht, C. H., Kwon, Y., Suto, E., Kohli, P. B., Liimatta, M., Barrett, K., Lloyd, J., Cain, G., Briggs, M., Addo, S., Salmon, G., Ubhayakar, S., Deshmukh, G., Shahidi-Latham, S. K., Quiason-Huynh, C. M., Jackman, J Tags: Research Articles Source Type: research

[Research Articles] Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc
Tissue engineering holds great promise for the treatment of advanced intervertebral disc degeneration. However, assessment of in vivo integration and mechanical function of tissue-engineered disc replacements over the long term, in large animal models, will be necessary to advance clinical translation. To that end, we developed tissue-engineered, endplate-modified disc-like angle ply structures (eDAPS) sized for the rat caudal and goat cervical spines that recapitulate the hierarchical structure of the native disc. Here, we demonstrate functional maturation and integration of these eDAPS in a rat caudal disc replacement mo...
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Gullbrand, S. E., Ashinsky, B. G., Bonnevie, E. D., Kim, D. H., Engiles, J. B., Smith, L. J., Elliott, D. M., Schaer, T. P., Smith, H. E., Mauck, R. L. Tags: Research Articles Source Type: research

[Research Articles] Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Fibrosis is the major determinant of morbidity and mortality in patients with nonalcoholic steatohepatitis (NASH) but has no approved pharmacotherapy in part because of incomplete understanding of its pathogenic mechanisms. Here, we report that hepatocyte Notch activity tracks with disease severity and treatment response in patients with NASH and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. Hepatocyte-specific Notch loss-of-function mouse models showed attenuated NASH-associated liver fibrosis, demonstrating causality to obesity-induced liver pathology. Conversely, forced activation of h...
Source: Science Translational Medicine - November 21, 2018 Category: Biomedical Science Authors: Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., Schwabe, R. F., Tabas, I., Valenti, L., Lavine, J. E., Pajvani, U. B. Tags: Research Articles Source Type: research

[Errata] Erratum for the Research Article: "mTORC1 Inhibition Is Required for Sensitivity to PI3K p110{alpha} Inhibitors in PIK3CA-Mutant Breast Cancer" by M. Elkabets, S. Vora, D. Juric, N. Morse, M. Mino-Kenudson, T. Muranen, J. Tao, A. B. Campos, J. Rodon, Y. H. Ibrahim, V. Serra, V. Rodrik-Outmezguine, S. Hazra, S. Singh, P. Kim, C. Quadt, M. Liu, A. Huang, N. Rosen, J. A. Engelman, M. Scaltriti, J. Baselga
(Source: Science Translational Medicine)
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Tags: Errata Source Type: research

[Editors' Choice] Charting the course of metastatic cells
An implantable biomaterial recruits rare tumor cells and enables long-term observation of microenvironmental evolution. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Singh, A. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Exosomal microRNA: The revolutionary endogenous Innerspace nanotechnology
T lymphocytes release exosomes containing specific microRNAs that cause apoptosis of pancreatic β cells in type 1 diabetes. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Santulli, G. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Illuminating Aurora dependencies
RB1 loss of function in small cell lung cancer causes dependency on Aurora kinases for survival, which can be targeted therapeutically. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Chonghaile, T. N. Tags: Editors ' Choice Source Type: research

[Research Articles] Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist
Oral administration of therapeutic peptides is hindered by poor absorption across the gastrointestinal barrier and extensive degradation by proteolytic enzymes. Here, we investigated the absorption of orally delivered semaglutide, a glucagon-like peptide-1 analog, coformulated with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) aminocaprylate] (SNAC) in a tablet. In contrast to intestinal absorption usually seen with small molecules, clinical and preclinical dog studies revealed that absorption of semaglutide takes place in the stomach, is confined to an area in close proximity to the tablet surface, and requires c...
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Buckley, S. T., Baekdal, T. A., Vegge, A., Maarbjerg, S. J., Pyke, C., Ahnfelt-Ronne, J., Madsen, K. G., Scheele, S. G., Alanentalo, T., Kirk, R. K., Pedersen, B. L., Skyggebjerg, R. B., Benie, A. J., Strauss, H. M., Wahlund, P.-O., Bjerregaard, S., Farka Tags: Research Articles Source Type: research

[Editorial] Patents and drug insurance: Clash of the Titans?
(Source: Science Translational Medicine)
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Phelps, C., Madhavan, G. Tags: Editorial Source Type: research

[Research Articles] Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma
The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), whic...
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Scafoglio, C. R., Villegas, B., Abdelhady, G., Bailey, S. T., Liu, J., Shirali, A. S., Wallace, W. D., Magyar, C. E., Grogan, T. R., Elashoff, D., Walser, T., Yanagawa, J., Aberle, D. R., Barrio, J. R., Dubinett, S. M., Shackelford, D. B. Tags: Research Articles Source Type: research

[Research Articles] Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells
Aging in humans is associated with increased hyperglycemia and insulin resistance (collectively termed IR) and dysregulation of the immune system. However, the causative factors underlying their association remain unknown. Here, using "healthy" aged mice and macaques, we found that IR was induced by activated innate 4-1BBL+ B1a cells. These cells (also known as 4BL cells) accumulated in aging in response to changes in gut commensals and a decrease in beneficial metabolites such as butyrate. We found evidence suggesting that loss of the commensal bacterium Akkermansia muciniphila impaired intestinal integrity, cau...
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Bodogai, M., OConnell, J., Kim, K., Kim, Y., Moritoh, K., Chen, C., Gusev, F., Vaughan, K., Shulzhenko, N., Mattison, J. A., Lee-Chang, C., Chen, W., Carlson, O., Becker, K. G., Gurung, M., Morgun, A., White, J., Meade, T., Perdue, K., Mack, M., Ferrucci, Tags: Research Articles Source Type: research

[Research Articles] Cell and fluid sampling microneedle patches for monitoring skin-resident immunity
Important cell populations reside within tissues and are not accessed by traditional blood draws used to monitor the immune system. To address this issue at an essential barrier tissue, the skin, we created a microneedle-based technology for longitudinal sampling of cells and interstitial fluid, enabling minimally invasive parallel monitoring of immune responses. Solid microneedle projections were coated by a cross-linked biocompatible polymer, which swells upon skin insertion, forming a porous matrix for local leukocyte infiltration. By embedding molecular adjuvants and specific antigens encapsulated in nanocapsules withi...
Source: Science Translational Medicine - November 14, 2018 Category: Biomedical Science Authors: Mandal, A., Boopathy, A. V., Lam, L. K. W., Moynihan, K. D., Welch, M. E., Bennett, N. R., Turvey, M. E., Thai, N., Van, J. H., Love, J. C., Hammond, P. T., Irvine, D. J. Tags: Research Articles Source Type: research

[Editors' Choice] Erratum for the Research Article: "Somatic PIK3CA mutations as a driver of sporadic venous malformations" by P. Castel, F. J. Carmona, J. Grego-Bessa, M. F. Berger, A. Viale, K. V. Anderson, S. Bague, M. Scaltriti, C. R. Antonescu, E. Baselga, J. Baselga
(Source: Science Translational Medicine)
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Tags: Editors ' Choice Source Type: research

[Research Articles] Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand
WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass in...
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Authors: Luther, J., Yorgan, T. A., Rolvien, T., Ulsamer, L., Koehne, T., Liao, N., Keller, D., Vollersen, N., Teufel, S., Neven, M., Peters, S., Schweizer, M., Trumpp, A., Rosigkeit, S., Bockamp, E., Mundlos, S., Kornak, U., Oheim, R., Amling, M., Schinke, T., Da Tags: Research Articles Source Type: research

[Editors' Choice] Exploiting human Tregs sweet tooth to improve cancer immunotherapy
TLR8 activation enhances cancer immunotherapy by reprograming of glucose metabolism in regulatory T cells. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Authors: Zeng, H. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Keeping pace with the mouse heart
A miniaturized and programmable pacemaker for mice demonstrates the feasibility of long-term cardiac pacing to study cardiac arrhythmias and heart failure. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Authors: Lavine, K. Tags: Editors ' Choice Source Type: research

[Editors' Choice] Music tunes the brain in autism
Music intervention alters brain activation and improves social communication skills in children with autism. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Authors: Jones, R. M. Tags: Editors ' Choice Source Type: research

[Research Articles] Enhanced detection of circulating tumor DNA by fragment size analysis
Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.4x). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed...
Source: Science Translational Medicine - November 7, 2018 Category: Biomedical Science Authors: Mouliere, F., Chandrananda, D., Piskorz, A. M., Moore, E. K., Morris, J., Ahlborn, L. B., Mair, R., Goranova, T., Marass, F., Heider, K., Wan, J. C. M., Supernat, A., Hudecova, I., Gounaris, I., Ros, S., Jimenez-Linan, M., Garcia-Corbacho, J., Patel, K., Tags: Research Articles Source Type: research