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https://www.readbyqxmd.com/read/29891568/a-5-enolpyruvylshikimate-3-phosphate-synthase-functions-as-a-transcriptional-repressor-in-populus
#1
Meng Xie, Wellington Muchero, Anthony C Bryan, Kelsey L Yee, Hao-Bo Guo, Jin Zhang, Timothy Tschaplinski, Vasanth R Singan, Erika Lindquist, Raja S Payyavula, Jaime Barros-Rios, Richard A Dixon, Nancy Engle, Robert W Sykes, Mark Davis, Sara Jawdy, Lee E Gunter, Olivia Thompson, Stephen P DiFazio, Luke M Evans, Kim Winkler, Cassandra Collins, Jeremy Schmutz, Hong Guo, Udaya Kalluri, Miguel Rodriguez, Kai Feng, Jin-Gui Chen, Gerald A Tuskan
Long-lived perennial plants, with distinctive habits of inter-annual growth, defense, and physiology, are of great economic and ecological importance. However, some biological mechanisms resulting from genome duplication and functional divergence of genes in these systems remain poorly studied. Here, we discovered an association between a poplar (Populus trichocarpa) 5-enolpyruvylshikimate 3-phosphate synthase gene (PtrEPSP) and lignin biosynthesis. Functional characterization of PtrEPSP revealed that this isoform possesses a helix-turn-helix motif in the N-terminus and can function as a transcriptional repressor that regulates expression of genes in the phenylpropanoid pathway in addition to performing its canonical biosynthesis function in the shikimate pathway...
June 11, 2018: Plant Cell
https://www.readbyqxmd.com/read/29873094/gestational-changes-in-buprenorphine-exposure-a-physiologically-based-pharmacokinetic-analysis
#2
Hongfei Zhang, Hari V Kalluri, Jaime R Bastian, Huijun Chen, Ali Alshabi, Steve N Caritis, Raman Venkataramanan
INTRODUCTION: Buprenorphine (BUP) is approved by the FDA for the treatment of opioid addiction. The current dosing regimen of BUP in pregnant women is based on recommendations designed for non-pregnant adults. However, physiological changes during pregnancy may alter BUP exposure and efficacy. The objectives of this study were to develop a physiologically-based-pharmacokinetic (PBPK) model for BUP in pregnant women, to predict changes in BUP exposure at different stages of pregnancy, and to demonstrate the utility of PBPK modelling in optimising BUP pharmacotherapy during pregnancy...
June 5, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29766399/consensus-guidelines-for-the-use-and-interpretation-of-angiogenesis-assays
#3
REVIEW
Patrycja Nowak-Sliwinska, Kari Alitalo, Elizabeth Allen, Andrey Anisimov, Alfred C Aplin, Robert Auerbach, Hellmut G Augustin, David O Bates, Judy R van Beijnum, R Hugh F Bender, Gabriele Bergers, Andreas Bikfalvi, Joyce Bischoff, Barbara C Böck, Peter C Brooks, Federico Bussolino, Bertan Cakir, Peter Carmeliet, Daniel Castranova, Anca M Cimpean, Ondine Cleaver, George Coukos, George E Davis, Michele De Palma, Anna Dimberg, Ruud P M Dings, Valentin Djonov, Andrew C Dudley, Neil P Dufton, Sarah-Maria Fendt, Napoleone Ferrara, Marcus Fruttiger, Dai Fukumura, Bart Ghesquière, Yan Gong, Robert J Griffin, Adrian L Harris, Christopher C W Hughes, Nan W Hultgren, M Luisa Iruela-Arispe, Melita Irving, Rakesh K Jain, Raghu Kalluri, Joanna Kalucka, Robert S Kerbel, Jan Kitajewski, Ingeborg Klaassen, Hynda K Kleinmann, Pieter Koolwijk, Elisabeth Kuczynski, Brenda R Kwak, Koen Marien, Juan M Melero-Martin, Lance L Munn, Roberto F Nicosia, Agnes Noel, Jussi Nurro, Anna-Karin Olsson, Tatiana V Petrova, Kristian Pietras, Roberto Pili, Jeffrey W Pollard, Mark J Post, Paul H A Quax, Gabriel A Rabinovich, Marius Raica, Anna M Randi, Domenico Ribatti, Curzio Ruegg, Reinier O Schlingemann, Stefan Schulte-Merker, Lois E H Smith, Jonathan W Song, Steven A Stacker, Jimmy Stalin, Amber N Stratman, Maureen Van de Velde, Victor W M van Hinsbergh, Peter B Vermeulen, Johannes Waltenberger, Brant M Weinstein, Hong Xin, Bahar Yetkin-Arik, Seppo Yla-Herttuala, Mervin C Yoder, Arjan W Griffioen
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation...
May 15, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29669940/generation-and-testing-of-clinical-grade-exosomes-for-pancreatic-cancer
#4
Mayela Mendt, Sushrut Kamerkar, Hikaru Sugimoto, Kathleen M McAndrews, Chia-Chin Wu, Mihai Gagea, Sujuan Yang, Elena V Rodriges Blanko, Qian Peng, Xiaoyan Ma, Joseph R Marszalek, Anirban Maitra, Cassian Yee, Katayoun Rezvani, Elizabeth Shpall, Valerie S LeBleu, Raghu Kalluri
Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. Here, we report on a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29473503/genetic-variants-identified-from-gwas-for-predisposition-to-type-2-diabetes-predict-sulfonylurea-drug-response
#5
N M Phani, M Vohra, P Adhikari, S K Nagri, U Shashikiran, S C D'Souza, P R R Kalluri, K Satyamoorthy, P S Rai
BACKGROUND: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology. OBJECTIVE: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas. METHOD: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited...
2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29111753/biogenic-nanostructured-porous-silicon-as-a-carrier-for-stabilization-and-delivery-of-natural-therapeutic-species
#6
Nguyen T Le, Jhansi R Kalluri, Armando Loni, Leigh T Canham, Jeffery L Coffer
Nanostructured mesoporous silicon (pSi) derived from the silicon-accumulator plant Tabasheer (Bambuseae) is demonstrated to serve as a potential carrier matrix for carrying and stabilizing naturally active, but otherwise metastable, therapeutic agents. Particularly, in this study, garlic oil containing phytochemicals (namely, allicin) that are capable of inhibiting Staphylococcus aureus (S. aureus) bacterial growth were incorporated into Tabasheer-derived porous silicon. Thermogravimetric analysis (TGA) indicated that relatively high amounts of the extract (53...
December 4, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28720851/microneedle-patch-delivery-of-influenza-vaccine-during-pregnancy-enhances-maternal-immune-responses-promoting-survival-and-long-lasting-passive-immunity-to-offspring
#7
E Stein Esser, Joanna A Pulit-Penaloza, Haripriya Kalluri, Devin McAllister, Elena V Vassilieva, Elizabeth Q Littauer, Nadia Lelutiu, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
Influenza virus causes life-threatening infections in pregnant women and their newborns. Immunization during pregnancy is the most effective means of preventing maternal and infant mortality/morbidity; however, influenza vaccination rates of pregnant women remain under 50%. Furthermore, the availability of vaccines in low-resource populations is limited. Skin immunization with microneedle patches (MN) is a novel and safe vaccination platform featuring thermostable vaccine formulations. Cold-chain independence and the potential for self-administration can expand influenza vaccination coverage in developing countries...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669739/an-evidence-based-recommendation-to-increase-the-dosing-frequency-of-buprenorphine-during-pregnancy
#8
Steve N Caritis, Jaime R Bastian, Hongfei Zhang, Hari Kalluri, Dennis English, Michael England, Stephanie Bobby, Raman Venkataramanan
BACKGROUND: Dose-adjusted plasma concentrations of buprenorphine are significantly decreased during pregnancy compared with the nonpregnant state. This observation suggests that pregnant women may need a higher dose of buprenorphine than nonpregnant individuals to maintain similar drug exposure (plasma concentrations over time after a dose). The current dosing recommendations for buprenorphine during pregnancy address the total daily dose of buprenorphine to be administered, but the frequency of dosing is not clearly addressed...
October 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28666680/the-safety-immunogenicity-and-acceptability-of-inactivated-influenza-vaccine-delivered-by-microneedle-patch-tiv-mnp-2015-a-randomised-partly-blinded-placebo-controlled-phase-1-trial
#9
Nadine G Rouphael, Michele Paine, Regina Mosley, Sebastien Henry, Devin V McAllister, Haripriya Kalluri, Winston Pewin, Paula M Frew, Tianwei Yu, Natalie J Thornburg, Sarah Kabbani, Lilin Lai, Elena V Vassilieva, Ioanna Skountzou, Richard W Compans, Mark J Mulligan, Mark R Prausnitz
BACKGROUND: Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. METHODS: The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders...
August 12, 2017: Lancet
https://www.readbyqxmd.com/read/28644693/supplemental-oxygen-in-interstitial-lung-disease-an-art-in-need-of-science
#10
Kerri A Johannson, Sachin R Pendharkar, Kirk Mathison, Charlene D Fell, Jordan A Guenette, Meena Kalluri, Martin Kolb, Christopher J Ryerson
Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in patients with advanced lung disease with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28285193/tolerability-usability-and-acceptability-of-dissolving-microneedle-patch-administration-in-human-subjects
#11
Jaya Arya, Sebastien Henry, Haripriya Kalluri, Devin V McAllister, Winston P Pewin, Mark R Prausnitz
To support translation of microneedle patches from pre-clinical development into clinical trials, this study examined the effect of microneedle patch application on local skin reactions, reliability of use and acceptability to patients. Placebo patches containing dissolving microneedles were administered to fifteen human participants. Microneedle patches were well tolerated in the skin with no pain or swelling and only mild erythema localized to the site of patch administration that resolved fully within seven days...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28121262/detection-of-mutant-kras-and-tp53-dna-in-circulating-exosomes-from-healthy-individuals-and-patients-with-pancreatic-cancer
#12
Sujuan Yang, Sara P Y Che, Paul Kurywchak, Jena L Tavormina, Liv B Gansmo, Pedro Correa de Sampaio, Michael Tachezy, Maximilian Bockhorn, Florian Gebauer, Amanda R Haltom, Sonia A Melo, Valerie S LeBleu, Raghu Kalluri
Pancreatic cancer presents with a dismal mortality rate and is in urgent need of methods for early detection with potential for timely intervention. All living cells, including cancer cells, generate exosomes. We previously discovered double stranded genomic DNA in exosomes derived from the circulation of pancreatic cancer patients, which enabled the detection of prevalent mutations associated with the disease. Here, we report a proof-of-concept study that demonstrates the potential clinical utility of circulating exosomal DNA for identification of KRASG 12 D and TP53R 273 H mutations in patients with pancreas-associated pathologies, including pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP) and intraductal papillary mucinous neoplasm (IPMN), and in healthy human subjects...
March 4, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27684478/single-plant-derived-nanotechnology-for-synergistic-antibacterial-therapies
#13
Jhansi R Kalluri, Roberto Gonzalez-Rodriguez, Phil S Hartman, Armando Loni, Leigh T Canham, Jeffery L Coffer
Multiple new approaches to tackle multidrug resistant infections are urgently needed and under evaluation. One nanotechnology-based approach to delivering new relevant therapeutics involves silicon accumulator plants serving as a viable silicon source in green routes for the fabrication of the nanoscale drug delivery carrier porous silicon (pSi). If the selected plant leaf components contain medicinally-active species as well, then a single substance can provide not only the nanoscale high surface area drug delivery carrier, but the drug itself...
2016: PloS One
https://www.readbyqxmd.com/read/26595531/mass-spectrometry-and-antibody-based-characterization-of-blood-vessels-from-brachylophosaurus-canadensis
#14
COMPARATIVE STUDY
Timothy P Cleland, Elena R Schroeter, Leonid Zamdborg, Wenxia Zheng, Ji Eun Lee, John C Tran, Marshall Bern, Michael B Duncan, Valerie S Lebleu, Dorothy R Ahlf, Paul M Thomas, Raghu Kalluri, Neil L Kelleher, Mary H Schweitzer
Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence...
December 4, 2015: Journal of Proteome Research
https://www.readbyqxmd.com/read/25895053/improved-immunogenicity-of-individual-influenza-vaccine-components-delivered-with-a-novel-dissolving-microneedle-patch-stable-at-room-temperature
#15
Elena V Vassilieva, Haripriya Kalluri, Devin McAllister, Misha T Taherbhai, E Stein Esser, Winston P Pewin, Joanna A Pulit-Penaloza, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study, we evaluated the immunogenicity of H1N1, H3N2, and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25 °C...
August 2015: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/25813522/genome-wide-profiling-of-p53-regulated-enhancer-rnas-uncovers-a-subset-of-enhancers-controlled-by-a-lncrna
#16
Nicolas Léveillé, Carlos A Melo, Koos Rooijers, Angel Díaz-Lagares, Sonia A Melo, Gozde Korkmaz, Rui Lopes, Farhad Akbari Moqadam, Ana R Maia, Patrick J Wijchers, Geert Geeven, Monique L den Boer, Raghu Kalluri, Wouter de Laat, Manel Esteller, Reuven Agami
p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regulators of chromatin dynamics, we hypothesized that p53-induced lncRNAs contribute to the activation of enhancers by p53. Among p53-induced lncRNAs, we identified LED and demonstrate that its suppression attenuates p53 function...
March 27, 2015: Nature Communications
https://www.readbyqxmd.com/read/25744228/enhanced-immune-responses-by-skin-vaccination-with-influenza-subunit-vaccine-in-young-hosts
#17
COMPARATIVE STUDY
Dimitrios G Koutsonanos, E Stein Esser, Sean R McMaster, Priya Kalluri, Jeong-Woo Lee, Mark R Prausnitz, Ioanna Skountzou, Timothy L Denning, Jacob E Kohlmeier, Richard W Compans
Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce...
September 8, 2015: Vaccine
https://www.readbyqxmd.com/read/24856586/depletion-of-carcinoma-associated-fibroblasts-and-fibrosis-induces-immunosuppression-and-accelerates-pancreas-cancer-with-reduced-survival
#18
Berna C Özdemir, Tsvetelina Pentcheva-Hoang, Julienne L Carstens, Xiaofeng Zheng, Chia-Chin Wu, Tyler R Simpson, Hanane Laklai, Hikaru Sugimoto, Christoph Kahlert, Sergey V Novitskiy, Ana De Jesus-Acosta, Padmanee Sharma, Pedram Heidari, Umar Mahmood, Lynda Chin, Harold L Moses, Valerie M Weaver, Anirban Maitra, James P Allison, Valerie S LeBleu, Raghu Kalluri
Pancreatic ductal adenocarcinoma (PDAC) is associated with marked fibrosis and stromal myofibroblasts, but their functional contribution remains unknown. Transgenic mice with the ability to delete αSMA(+) myofibroblasts in pancreatic cancer were generated. Depletion starting at either noninvasive precursor (pancreatic intraepithelial neoplasia) or the PDAC stage led to invasive, undifferentiated tumors with enhanced hypoxia, epithelial-to-mesenchymal transition, and cancer stem cells, with diminished animal survival...
June 16, 2014: Cancer Cell
https://www.readbyqxmd.com/read/23716260/a-naturalistic-approach-to-the-cocktail-party-problem
#19
Ervin R Hafter, Jing Xia, Sridhar Kalluri
While studies of simple acoustic features have provided excellent bases for models of spatial hearing, we are seeking, here, to create a new paradigm for examination of shared attention and scene analysis in natural environments, where the listener is confronted with semantic information from multiple sources. In this new simulation of the cocktail party problem, a subject (S) is questioned, on-line, about information heard in multiple simultaneous stories spoken by different talkers. Questions based on brief passages in the stories are presented visually for manual response...
2013: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/23580202/type-xviii-collagen-is-essential-for-survival-during-acute-liver-injury-in-mice
#20
Michael B Duncan, Changqing Yang, Harikrishna Tanjore, Patrick M Boyle, Doruk Keskin, Hikaru Sugimoto, Michael Zeisberg, Bjorn R Olsen, Raghu Kalluri
The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death...
July 2013: Disease Models & Mechanisms
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