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Science Translational Medicine

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https://www.readbyqxmd.com/read/28539477/bacterial-colonization-and-succession-in-a-newly-opened-hospital
#1
Simon Lax, Naseer Sangwan, Daniel Smith, Peter Larsen, Kim M Handley, Miles Richardson, Kristina Guyton, Monika Krezalek, Benjamin D Shogan, Jennifer Defazio, Irma Flemming, Baddr Shakhsheer, Stephen Weber, Emily Landon, Sylvia Garcia-Houchins, Jeffrey Siegel, John Alverdy, Rob Knight, Brent Stephens, Jack A Gilbert
The microorganisms that inhabit hospitals may influence patient recovery and outcome, although the complexity and diversity of these bacterial communities can confound our ability to focus on potential pathogens in isolation. To develop a community-level understanding of how microorganisms colonize and move through the hospital environment, we characterized the bacterial dynamics among hospital surfaces, patients, and staff over the course of 1 year as a new hospital became operational. The bacteria in patient rooms, particularly on bedrails, consistently resembled the skin microbiota of the patient occupying the room...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539476/response-to-comment-on-epigenetic-activation-of-the-drug-transporter-oct2-sensitizes-renal-cell-carcinoma-to-oxaliplatin
#2
Xiaoli Zheng, Yanqing Liu, Qinqin Yu, Hua Wang, Fuqing Tan, Qianying Zhu, Lingmin Yuan, Huidi Jiang, Su Zeng, Lushan Yu
No abstract text is available yet for this article.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539475/the-brain-microenvironment-mediates-resistance-in-luminal-breast-cancer-to-pi3k-inhibition-through-her3-activation
#3
David P Kodack, Vasileios Askoxylakis, Gino B Ferraro, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Z Alexander Cao, Rakesh R Ramjiawan, Divya Bezwada, Bhushankumar Patel, Yongchul Song, Carlotta Costa, Kamila Naxerova, Christina S F Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G Duda, C Ryan Miller, Marni B Siegel, Carey K Anders, Melinda Sanders, Monica V Estrada, Robert Schlegel, Carlos L Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A Engelman, Rakesh K Jain
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539474/a-gema-of-a-personalized-medicine-strategy
#4
Monica Venere
A screening method can identify tumors susceptible to synthetic lethality via PARP inhibition.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539473/stable-hormones-for-stable-moods
#5
Vasiliki Michopoulos
The rise in ovarian hormones triggers premenstrual dysphoric disorder symptoms in women.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539472/dive-deep-stay-focused
#6
Hadar Lev-Tov
Noninvasive ultra-broadband optoacoustic mesoscopy skin imaging technology may provide objective assessment of skin disease.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539471/nanomedicine-goes-to-school
#7
Christopher M Jewell
Integration of engineering and immunological tools proposes design guidelines for nanoparticles that direct T cells toward specific phenotypes to control autoimmune disease.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#8
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539469/multiparametric-plasma-ev-profiling-facilitates-diagnosis-of-pancreatic-malignancy
#9
Katherine S Yang, Hyungsoon Im, Seonki Hong, Ilaria Pergolini, Andres Fernandez Del Castillo, Rui Wang, Susan Clardy, Chen-Han Huang, Craig Pille, Soldano Ferrone, Robert Yang, Cesar M Castro, Hakho Lee, Carlos Fernandez Del Castillo, Ralph Weissleder
Pancreatic ductal adenocarcinoma (PDAC) is usually detected late in the disease process. Clinical workup through imaging and tissue biopsies is often complex and expensive due to a paucity of reliable biomarkers. We used an advanced multiplexed plasmonic assay to analyze circulating tumor-derived extracellular vesicles (tEVs) in more than 100 clinical populations. Using EV-based protein marker profiling, we identified a signature of five markers (PDAC(EV) signature) for PDAC detection. In our prospective cohort, the accuracy for the PDAC(EV) signature was 84% [95% confidence interval (CI), 69 to 93%] but only 63 to 72% for single-marker screening...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28539468/comment-on-epigenetic-activation-of-the-drug-transporter-oct2-sensitizes-renal-cell-carcinoma-to-oxaliplatin
#10
Stefan Winter, Pascale Fisel, Florian Büttner, Anne T Nies, Arnulf Stenzl, Jens Bedke, Matthias Schwab, Elke Schaeffeler
No abstract text is available yet for this article.
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#11
Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E Lemieux, Jonathan D Brown, Deepak Srivastava, James E Bradner, Timothy A McKinsey, Saptarsi M Haldar
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515340/turning-back-the-clock
#12
Ashley H Shoemaker
Increased DNA breaks in aging skeletal muscle activate the DNA-PK pathway, whereas blocking this pathway improves mitochondrial density, physical fitness, body weight, and insulin resistance in mice.
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515339/chemotherapy-treated-cells-go-up-in-flames
#13
Kristopher Sarosiek
Apoptosis induced by chemotherapies can also trigger proinflammatory pyroptosis.
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515338/an-eye-for-rhythm
#14
Jeffrey Haspel
A new analytical method allows reconstruction of circadian gene expression in human biopsy samples.
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515337/hung-over-maybe-it-s-your-overactive-microglia
#15
Huimahn Alex Choi
Acute ethanol intake is associated with a mild suppression of microglial activity followed by a more robust inflammatory reaction during the withdrawal period.
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515336/the-effects-of-micronutrient-deficiencies-on-bacterial-species-from-the-human-gut-microbiota
#16
Matthew C Hibberd, Meng Wu, Dmitry A Rodionov, Xiaoqing Li, Jiye Cheng, Nicholas W Griffin, Michael J Barratt, Richard J Giannone, Robert L Hettich, Andrei L Osterman, Jeffrey I Gordon
Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people. Although the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the gut microbiota of developing or adult humans. Therefore, we established a community of cultured, sequenced human gut-derived bacterial species in gnotobiotic mice and fed the animals a defined micronutrient-sufficient diet, followed by a derivative diet devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient diet...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515335/in-situ-bone-tissue-engineering-via-ultrasound-mediated-gene-delivery-to-endogenous-progenitor-cells-in-mini-pigs
#17
Maxim Bez, Dmitriy Sheyn, Wafa Tawackoli, Pablo Avalos, Galina Shapiro, Joseph C Giaconi, Xiaoyu Da, Shiran Ben David, Jayne Gavrity, Hani A Awad, Hyun W Bae, Eric J Ley, Thomas J Kremen, Zulma Gazit, Katherine W Ferrara, Gadi Pelled, Dan Gazit
More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28515334/central-acting-therapeutics-alleviate-respiratory-weakness-caused-by-heart-failure-induced-ventilatory-overdrive
#18
Andrew J Foster, Mathew J Platt, Jason S Huber, Ashley L Eadie, Alicia M Arkell, Nadya Romanova, David C Wright, Todd E Gillis, Coral L Murrant, Keith R Brunt, Jeremy A Simpson
Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea and exertional fatigue. Most studies have focused on advanced stages of HF, leaving the cause unresolved. The long-standing theory is that pulmonary edema imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF patients rarely exhibit pulmonary edema. We investigated how diaphragmatic weakness develops in two mouse models of pressure overload-induced HF. As in HF patients, both models had increased eupneic respiratory pressures and ventilatory drive...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28490672/phenome-wide-scanning-identifies-multiple-diseases-and-disease-severity-phenotypes-associated-with-hla-variants
#19
Jason H Karnes, Lisa Bastarache, Christian M Shaffer, Silvana Gaudieri, Yaomin Xu, Andrew M Glazer, Jonathan D Mosley, Shilin Zhao, Soumya Raychaudhuri, Simon Mallal, Zhan Ye, John G Mayer, Murray H Brilliant, Scott J Hebbring, Dan M Roden, Elizabeth J Phillips, Joshua C Denny
Although many phenotypes have been associated with variants in human leukocyte antigen (HLA) genes, the full phenotypic impact of HLA variants across all diseases is unknown. We imputed HLA genomic variation from two populations of 28,839 and 8431 European ancestry individuals and tested association of HLA variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA allele phenotype associations were significant in both discovery and replication cohorts, the strongest being HLA-DQB1*03:02 and type 1 diabetes...
May 10, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28490671/matched-preclinical-designs-for-improved-translatability
#20
EDITORIAL
Tero Aittokallio, Andreas Scherer, Matti Poutanen, Leonard P Freedman
A more stratified preclinical design strategy will increase the statistical power and reproducibility of animal studies and their translatability.
May 10, 2017: Science Translational Medicine
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